Search

Purpose Stress urinary incontinence is a postoperative complication occurring in patients with pelvic organ prolapse (POP). Although the 1-hour pad test measures the degree of urinary incontinence qualitatively and quantitatively, some elderly women undergoing POP surgery do not have the daily activities of living to perform the pad test. Therefore, we examined whether the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) could be used as an alternative tool for pad tests. Methods We retrospectively evaluated 132 patients with POP. In our hospital, 57 patients were treated by laparoscopic sacrocolpopexy (LSC), whereas 75 were treated by transvaginal mesh surgery (TVM). We measured the changes in symptoms preand postoperatively using the ICIQ-SF and 1-hour pad weight testing, and investigated the correlation between the total plus component question scores of the ICIQ-SF and 1-hour pad weight. Results The preoperative ICIQ total scores in all patients decreased significantly as the amount of leakage on the 1-hour pad weight decreased. The component question scores also decreased significantly with decreasing levels of 1-hour pad weight. The LSC and TVM groups had decreased ICIQ-SF total and component question scores as pad weight decreased. At 12 months postoperatively, the ICIQ total scores in all patients significantly declined as the amount of leakage on the 1-hour pad weight decreased. In the LSC group, the ICIQ-SF total and component question scores also decreased with decreased pad weight, but the differences were not always significant between ICIQ scores and pad weight. In the TVM group, the ICIQ-SF total and component question scores also significantly decreased as the pad weight decreased. Conclusions The ICIQ-SF could be an appropriate substitute for the 1-hour pad weight testing in predicting the severity of urinary incontinence. In the future, we hope to predict the level of urine leakage based on the ICIQ-SF score.

Introduction: NSCLC is a leading cause of cancer-related mortality worldwide. Specific genetic alterations, such as MET exon 14 (METex14) skipping, have been identified in NSCLC, allowing targeted therapy. Tepotinib, a highly selective MET inhibitor, has displayed promise in patients with advanced NSCLC. Nevertheless, challenges arise when identifying treatment strategies for patients with discordant results regarding METex14 skipping detection between diagnostic tests. Methods: We investigated patients with NSCLC and discordant results for METex14 skipping between the Oncomine Dx Target Test (ODxTT) and ArcherMET. Clinical response, adverse events, and the duration of tepotinib treatment were assessed, and statistical analysis was performed. Results: Among the 19 patients deemed METex14 skipping positive by ODxTT, only 10 had concordant results with ArcherMET. The number of METex14 skipping reads detected by ODxTT was significantly lower in discordant cases. Of the 19 patients, 14 received tepotinib, and comparable response and disease control rates were observed in both concordant and discordant cases. The duration of treatment did not significantly differ between the two groups. Conclusions: Our findings suggest that tepotinib has comparable therapeutic effects in patients with METex14 skipping-positive NSCLC irrespective of the concordance of results between ODxTT and ArcherMET. Tepotinib is a possible treatment option for patients with METex14 skipping, even in patients with discordant test results.

Objective: The incidence of left-sided inferior vena cava (IVC) is extremely low. However, without a preoperative diagnosis of left-sided IVC, the risk of intraoperative vascular injury during para-aortic lymph node (PAN) lymphadenectomy is high. Case report: Herein, we present two cases in which left-sided IVCs were diagnosed using preoperative imaging. PAN lymphadenectomies were safely performed in these patients with endometrial cancer. In the first case, the left-sided IVC crossed the abdominal aorta after the left renal and gonadal veins had drained into it and joined the right renal vein. In the second case, the left-sided IVC crossed the abdominal aorta after the left renal and gonadal veins flowed into it and the ascending lumbar vein flowed into the right side. Conclusion: These cases demonstrate that even in the presence of vascular malformations, PAN lymphadenectomy can be performed safely by employing preoperative anatomical imaging analysis and judicious intraoperative surgical maneuvers to avoid vascular injury.

Magnesium rechargeable batteries (MRBs) are ones of promising low-cost, safe, and high-energy post-lithium-ion batteries. However, critical issues still lie both in electrolytes and cathodes, despite 20 years since the first report of prototype MRB. Difficulty in the utilization of high-energy oxide-type cathode materials derives from their low ion-diffusion and electrical conductivity, leading to low reversible capacity. Herein, various nanotechnologies for spinel oxide cathode materials and cathode/electrolyte interface are displayed to operate the MRB, even at room temperature conditions. Surface-modified ultraporous spinel nanoparticles exhibit electrochemical magnesium intercalation, achieving the theoretical capacity. In addition, the decomposition reaction of the ether-based electrolyte at the highly reactive cathode surface is suppressed by the Mg2+-conductive coating layer. These cathode material designs will open up new technologies for the practical application of room-temperature MRB.

Abstract Cytokine release syndrome (CRS) is a severe and life‐threatening toxicity typically reported in chimeric antigen receptor T cell therapy and is rarely reported in immune checkpoint inhibitor (ICI) therapy. This study reports the case of a 75‐year‐old Japanese woman who received nivolumab plus ipilimumab therapy for the postoperative recurrence of non‐small cell lung cancer. She was admitted to our hospital with fever, hypotension, hepatic disorder, and thrombocytopenia. We observed slight skin rashes on her neck on admission, which spread rapidly across her body within a few days. We diagnosed CRS complicated by severe rashes. CRS symptoms were resolved with corticosteroid therapy, and did not recur thereafter. CRS is a rare, but important, immune‐related adverse event associated with ICI therapy.

We apply the hydroflux method as a potential cathode-coating process for solid-state batteries. The garnet-type Li-ion conductor Li6.4La3Zr1.4Ta0.6O12 reacts with the precursor material of LiCoO2. Water molecules in the molten alkaline hydroxide initiate Li+/H+ ion exchange and dissolution of the Zr4+ species. The NASICON-type lithium-ion conductor LATP also reacts with molten hydroxide owing to the formation of soluble species of Al(OH)4− under high pH conditions. Perovskite-type Li0.33La0.55TiO3 is stable under the hydroflux condition because titanium and lanthanum do not form soluble species in alkaline solution. The chemical compatibility of the solid-state electrolyte is mostly estimated using Pourbaix diagram of each element in the system. The solid-state electrolyte containing only insoluble species in an alkaline solution is preferable for the hydroflux cathode-coating process.

Abstract The 2021 M w 7.1 and 2022 M w 7.4 Fukushima-oki earthquakes ruptured adjacent regions in the subducting slab, which gave us a good opportunity to better understand the rupture process of an intraslab earthquake and the fault system in a subducting slab hosting such large earthquakes. We developed source models of the two earthquakes by constructing fault models based on the distributions of relocated aftershocks and performing joint source inversion using strong motion, teleseismic and geodetic data. The results showed that the 2021 earthquake was initiated by the west-northwest dipping fault and that it then ruptured the east-southeast dipping fault. The rupture propagated to the southwest and up-dip directions. For the 2022 earthquake, the rupture primarily propagated to the north-northeast and up-dip directions on another east-southeast dipping fault, but a delayed rupture occurred around the hypocenter approximately 12 s after the rupture initiation. This was probably due to the complex fault system around the hypocenter. Our source models accurately reproduced observed data for both earthquakes, indicating that the fault geometry was appropriate. We found that the source faults of these earthquakes had similarities to faults in the outer-rise region, which suggests that the 2021 and 2022 earthquakes occurred on faults that originally formed in the outer-rise region and reactivated in the subducting slab. Such a fault system in the subducting slab was probably one of the factors that controlled the rupture processes of the two earthquakes. Graphical Abstract

IntroductionGrowing anecdotal evidence suggests the feasibility of robotic intervention for people who suffer from disorders related to state anxiety. Few studies have been conducted on utilizing robots for persons who stutter (PWS). The present study examines the feasibility of using a robot for speech therapy for PWS.MethodsWe prepared four settings (i.e., interviews with unfamiliar persons, interviews with unfamiliar communication robots, reading sentences aloud with a tandem robot that can utter the same words as a user by repeating the user’s voice after a short delay, and reading sentences aloud while being alone). We assessed the potential of the robots as both interlocutors and practice partners in training with delayed auditory feedback (DAF) for PWS. Moreover, we assessed the relationship between the trait of stuttering and the participants’ affinity to the robots.ResultsEleven PWS participated in the study. Eight (72.7%) participants had fewer stuttering-related psychological symptoms when they communicated with robots than when they communicated with humans. Spearman’s rank correlation analysis revealed that there was a significant negative correlation between the Modified Erickson Communication Attitude scale (S-24) and the difference between the scores for stuttering-related psychological symptoms pertaining to the communication robot and humans (p

Abstract Background Genomic profile analysis using next‐generation sequencing can potentially elucidate the pathogenesis of rare cancers. Ductal adenocarcinoma, a rare subtype of prostate cancer, has an aggressive nature. This is the first study to analyze the genomic profile of ductal adenocarcinoma in an Asian population. Methods We identified 12 patients newly diagnosed with ductal adenocarcinoma of the prostate at two hospitals, and nine patients (75.0%) had the pure type. Genomic assessment was performed using either the PleSSision testing platform or FoundationOne CDx. Results At least one genomic alteration occurred in 11 patients (91.7%), and the most frequently mutated gene was tumor suppressor protein p53 (TP53), which was found in six cases (50.0%). Alterations characteristic of this cohort were found in four cases (33.3%) of retinoblastoma transcriptional corepressor 1 (RB1), which was only observed in the pure type. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3‐kinase (PI3K) pathway (n = 3; 25.0%) and Wnt‐β‐catenin pathway (n = 5; 41.7%) was comparable, but no alterations in the DNA damage repair (DDR) pathway were observed. None of the patients presented high tumor mutation burden or microsatellite instability. Conclusions We found that the Asian cohort with ductal adenocarcinoma had actionable alterations, and a high frequency of alterations in TP53 and RB1 reflected the aggressive nature of the tumor. Genetic analysis using next‐generation sequencing is expected to help elucidate the pathogenesis of ductal adenocarcinoma.

Hirotsu, Kakizaki et al. assess the presence of pneumonia and pathogenesis during infection with different SARS-CoV-2 variants. The prevalence of pneumonia differs depending on the infectious variant, with the lowest prevalence and mild lung pathogenesis following infection with BA.2.

Spectrum sharing in the spatial domain among the plurality of wireless communication systems should be addressed due to its exhaustion. We previously conceptualized a spectrum superposing enabled by subcarrier transmission power assignment (STPA) and blind adaptive array (BAA), where co-channel interference can be suppressed even without a priori information of interferer. However, it requires knowledge of input signal-to-interference power ratio (SIR) to realize completely blind operation. This paper proposes a blind SIR estimation framework by convolutional neural network (CNN) using power spectrum images. Simulation verifies the proposed scheme can maximize throughput performance based on SIR classification results with 97% accuracy.

The transition between MgM2O4 (M = Mn, Fe, Co) spinels (SPs) and MgMO2 rock salts (RS) has attracted considerable interest for cathode reactions in future magnesium battery applications. To improve the cycling performance, one should suppress the consumption of solvent molecules. In this study, we investigated ether solvent decomposition on MgM2O4 SP and MgMO2 RS surfaces using first-principles calculations. We found that the C–H bond dissociation of ether molecules on the SP surface was exothermic, while the C–H bond dissociation on RS and C–O bond dissociation on both SP and RS surfaces were endothermic, irrespective of the transition metal element. The products of C–H dissociation reactions at the SP surfaces have occupied states originating from SP surfaces inside the bandgap. As the SP surface is destabilized by C–H dissociation, the electrons at this level can be extracted as an oxidative current.

Abstract Increased intra-individual variability of a variety of biomarkers is generally associated with poor health and reflects physiological dysregulation. Correlations among these biomarker variabilities should then represent interactions among heterogeneous biomarker regulatory systems. Herein, in an attempt to elucidate the network structure of physiological systems, we probed the inter-variability correlations of 22 biomarkers. Time series data on 19 blood-based and 3 hemodynamic biomarkers were collected over a one-year period for 334 hemodialysis patients, and their variabilities were evaluated by coefficients of variation. The network diagram exhibited six clusters in the physiological systems, corresponding to the regulatory domains for metabolism, inflammation, circulation, liver, salt, and protein. These domains were captured as latent factors in exploratory and confirmatory factor analyses (CFA). The 6-factor CFA model indicates that dysregulation in each of the domains manifests itself as increased variability in a specific set of biomarkers. Comparison of a diabetic and non-diabetic group within the cohort by multi-group CFA revealed that the diabetic cohort showed reduced capacities in the metabolism and salt domains and higher variabilities of the biomarkers belonging to these domains. The variability-based network analysis visualizes the concept of homeostasis and could be a valuable tool for exploring both healthy and pathological conditions.

Abstract Background Patients with end-stage kidney disease (ESKD) face higher risks of life-threatening events including cardiovascular disease. Various risk factors are identified as agents influencing the life prognosis of ESKD patients. Herein, we evaluated the risk factors related to the outcomes of Japanese patients with dialysis induction. We present the study protocol, the patients’ baseline characteristics, and their outcomes. Methods The Ibaraki Dialysis Initiation Cohort (iDIC) Study is a prospective multi-center cohort study in collaboration with 60 tertiary-care facilities in Ibaraki Prefecture, Japan. We collected baseline data from clinical records and analyzed blood and urine samples of these facilities’ patients with diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis (CGN). The study’s primary outcome was the survival rate at 24 months after dialysis induction. We performed a Kaplan-Meier analysis for cumulative survival and a Cox proportional hazards analysis for all-cause mortality and hospitalization. Results We analyzed 636 patients’ cases (424 males, 212 females, age 67.4 ± 13.1 yrs. [mean ± SD]). We compared the patients’ baseline data with those of similar cohort studies. As the primary kidney disease, 327 cases (51.4%) were diagnosed as diabetic nephropathy, 101 (15.9%) as hypertensive nephrosclerosis, and 114 (17.9%) as CGN. The mean serum creatinine value was 9.1 ± 2.9 mg/dL. The mean estimated glomerular filtration rate was 5.6 ± 1.8 mL/min/1.73m2. The cumulative survival rates at 6 months and 24 months after dialysis induction were 95.2 and 87.7%, respectively. The cumulative survival rate was significantly lower with increasing age. A Cox proportional hazards regression analysis demonstrated that high age was significantly associated with all-cause mortality. Conclusions Regarding the clinical characteristics of these newly induced dialysis patients, the same trend as in other cohort studies was observed. Another study is underway to explore prognostic factors based on the iDIC Study’s findings.

Abstract This study proposes a new method for the uncertainty estimation of coseismic slip distribution on the plate interface deduced from real-time global navigation satellite system (GNSS) data and explores its application for tsunami inundation prediction. Jointly developed by the Geospatial Information Authority of Japan and Tohoku University, REGARD (REal-time GEONET Analysis system for Rapid Deformation monitoring) estimates coseismic fault models (a single rectangular fault model and slip distribution model) in real time to support tsunami prediction. The estimated results are adopted as part of the Disaster Information System, which is used by the Cabinet Office of the Government of Japan to assess tsunami inundation and damage. However, the REGARD system currently struggles to estimate the quantitative uncertainty of the estimated result, although the obtained result should contain both observation and modeling errors caused by the model settings. Understanding such quantitative uncertainties based on the input data is essential for utilizing this resource for disaster response. We developed an algorithm that estimates the coseismic slip distribution and its uncertainties using Markov chain Monte Carlo methods. We focused on the Nankai Trough of southwest Japan, where megathrust earthquakes have repeatedly occurred, and used simulation data to assume a Hoei-type earthquake. We divided the 2951 rectangular subfaults on the plate interface and designed a multistage sampling flow with stepwise perturbation groups. As a result, we successfully estimated the slip distribution and its uncertainty at the 95% confidence interval of the posterior probability density function. Furthermore, we developed a new visualization procedure that shows the risk of tsunami inundation and the probability on a map. Under the algorithm, we regarded the Markov chain Monte Carlo samples as individual fault models and clustered them using the k-means approach to obtain different tsunami source scenarios. We then calculated the parallel tsunami inundations and integrated the results on the map. This map, which expresses the uncertainties of tsunami inundation caused by uncertainties in the coseismic fault estimation, offers quantitative and real time insights into possible worst-case scenarios. Graphical Abstract

Abstract Background The use of whole-genome sequencing in clinical practice has revealed variable genomic characteristics across cancer types, one of which is whole-genome doubling (WGD), which describes the duplication of a complete set of chromosomes. Yet it is relatively rare in prostate cancer and no such case has ever been reported in Japanese patients. Case presentation A 54-year-old patient with prostatic adenocarcinoma with bone and lymph node metastases was started on androgen-deprivation therapy. As the prostate cancer turned castration-resistant, multimodal therapies including taxane- and platinum-based chemotherapy, androgen-receptor antagonist inhibitors, radiotherapy and radium-233 were introduced. Good controls of serum prostate-specific antigen (PSA) level and bone metastases were achieved for more than 13 years since after the initial treatment. During the treatment, a metastatic lymph node biopsy was performed to confirm the tumor histology, and spinal decompression surgery were performed for spinal compression due to lumber vertebral metastases. The immunohistochemical analysis identified PSA and androgen receptor positive tumor cells in both metastatic lesions, while no variable cancer cells were detected in the prostate on second biopsy. Whole-genome sequencing was performed on the biopsied metastatic lymph node in search for another possible treatment and it revealed that the tumor had WGD and CDK12 mutation. The WGD-positive tumor cells contained large and polymorphic nucleus, presumably reflecting on the ploidy abnormality of the chromosomes. Conclusions This report is the first case of a Japanese patient presenting with WGD, who survived more than 13 years with multimodal chemotherapies and radiotherapies.

Introduction Primary or metastatic urethral tumors are extremely rare. However, treatment strategies differ between primary and metastatic tumors. Therefore, establishing an accurate diagnosis is critically needed for initiating timely and appropriate therapy. Case presentation We describe the case of a 79‐year‐old man with prostate cancer treated with radiotherapy and androgen deprivation therapy. He presented with macroscopic hematuria as a symptom of anterior urethral tumor at follow‐up. Endoscopic tumor resection was performed. Hematoxylin and eosin staining showed adenocarcinoma component. Immunohistochemical staining revealed presence of metastatic prostate cancer to the urethra. Conclusion Regarding urethral tumors diagnosis, urologists should consider the possibility of metastasis from prostate cancer and perform immunohistochemical examination for establishing accurate diagnosis. Furthermore, if androgen deprivation therapy fails to suppress symptoms, radiotherapy or urethrectomy might be considered.

Cold atmospheric plasma (CAP) has been studied and clinically applied to treat chronic wounds, cancer, periodontitis, and other diseases. CAP exerts cytotoxic, bactericidal, cell-proliferative, and anti-inflammatory effects on living tissues by generating reactive species. Therefore, CAP holds promise as a treatment for diseases involving chronic inflammation and bacterial infections. However, the cellular mechanisms underlying these anti-inflammatory effects of CAP are still unclear. Thus, this study aimed to elucidate the anti-inflammatory mechanisms of CAP in vitro. The human acute monocytic leukemia cell line, THP-1, was stimulated with lipopolysaccharide and irradiated with CAP, and the cytotoxic effects of CAP were evaluated. Time-course differentiation of gene expression was analyzed, and key transcription factors were identified via transcriptome analysis. Additionally, the nuclear localization of the CAP-induced transcription factor was examined using western blotting. The results indicated that CAP showed no cytotoxic effects after less than 70 s of irradiation and significantly inhibited interleukin 6 (IL6) expression after more than 40 s of irradiation. Transcriptome analysis revealed many differentially expressed genes (DEGs) following CAP irradiation at all time points. Cluster analysis classified the DEGs into four distinct groups, each with time-dependent characteristics. Gene ontology and gene set enrichment analyses revealed CAP-induced suppression of IL6 production, other inflammatory responses, and the expression of genes related to major histocompatibility complex (MHC) class II. Transcription factor analysis suggested that nuclear factor erythroid 2-related factor 2 (NRF2), which suppresses intracellular oxidative stress, is the most activated transcription factor. Contrarily, regulatory factor X5, which regulates MHC class II expression, is the most suppressed transcription factor. Western blotting revealed the nuclear localization of NRF2 following CAP irradiation. These data suggest that CAP suppresses the inflammatory response, possibly by promoting NRF2 nuclear translocation.

Summary: Clustered protocadherin is a family of cell-surface recognition molecules implicated in neuronal connectivity that has a diverse isoform repertoire and homophilic binding specificity. Mice have 58 isoforms, encoded by Pcdhα, β, and γ gene clusters, and mutant mice lacking all isoforms died after birth, displaying massive neuronal apoptosis and synapse loss. The current hypothesis is that the three specific γC-type isoforms, especially γC4, are essential for the phenotype, raising the question about the necessity of isoform diversity. We generated TC mutant mice that expressed the three γC-type isoforms but lacked all the other 55 isoforms. The TC mutants died immediately after birth, showing massive neuronal death, and γC3 or γC4 expression did not prevent apoptosis. Restoring the α- and β-clusters with the three γC alleles rescued the phenotype, suggesting that along with the three γC-type isoforms, other isoforms are also required for the survival of neurons and individual mice.

Abstract Background Ductal adenocarcinoma and neuroendocrine cancer are rare subtypes of prostate cancer with poor prognosis and limited therapeutic options. We present the first case of ductal adenocarcinoma having a neuroendocrine phenotype. Case presentation A 63-year-old man presented with gross hematuria and urinary retention, and his serum prostate-specific antigen level was 4.58 ng/mL. We performed transurethral resection of the prostate, and the diagnosis was ductal adenocarcinoma with a Gleason score of 5 + 4 for acinar adenocarcinoma. Magnetic resonance imaging showed local invasion of left lobe of the prostate and bone metastasis of the left trochanteric section of the femur. Multidisciplinary treatments such as androgen deprivation therapy, chemoradiation therapy, and surgery for metastatic lesions have led to long-term survival. Since next-generation sequencing revealed PTEN and RB1 co-loss and TP53 mutations, we re-evaluated the immunohistochemistry and he was found to be positive for synaptophysin. Conclusions This is the first Japanese case of ductal adenocarcinoma with a neuroendocrine phenotype. Genetic analysis may help not only guide the therapeutic strategies, but also sometimes with the diagnosis.

Abstract Objective To investigate whether dose reductions in cisplatin due to renal dysfunction were associated with worse clinical outcomes in metastatic urothelial carcinoma (UC) patients. Patients and methods One hundred and fifty one metastatic UC patients who received first‐line gemcitabine plus cisplatin (GC) salvage chemotherapy without a previous history of peri‐surgical chemotherapy were included in this retrospective study. Patients with endogenous creatinine clearance of 60 mL/min or more were treated with a full dose of cisplatin, while those with 45‐59 and 30‐44 mL/min were treated with 75% and 50% doses, respectively. Patients were divided into three groups based on the average administered dose of cisplatin of 100% (Group A, N = 43), 99%‐75% (Group B, N = 59), and less than 75% (Group C, N = 49), and therapeutic responses and the toxicity of GC were compared. Results Complete response rates were 9.3%, 13.6%, and 14.3% in groups A, B, and C, respectively. One‐year progression‐free survival rates were 22.9%, 31.1%, and 36.7% in groups A, B, and C with no significant differences. One‐year cancer‐specific survival rates were 56.1%, 71.1%, and 68.3% in groups A, B, and C with no significant differences. A multivariate Cox's regression analysis showed that the dose of cisplatin was not an independent prognostic factor for disease progression and cancer death. Furthermore, there were no significant differences in the incidence of severe adverse events. Conclusions Dose reductions in cisplatin due to renal dysfunction did not worsen clinical outcomes for metastatic UC.

Abstract Macular pucker, also known as an epiretinal membrane, sometimes forms after surgical repair of a rhegmatogenous retinal detachment (RRD) and can decrease visual acuity and cause aniseikonia. However, few reports are evaluating the risk factors of macular pucker using multivariate analysis. To evaluate the risk factors for macular pucker after RRD surgery, 226 patients who underwent RRD surgery and were monitored for greater than 12 months (23.2 ± 6.4 months) after surgery were analyzed retrospectively. Of these cases, macular pucker developed in 26 cases. Multiple logistic regression models of 22 clinical characteristics were performed. An increased risk of macular pucker after RRD surgery was significantly associated with preoperative vitreous haemorrhage (Odds ratio (OR), 4.71; 95% CI 1.19–18.62), multiple retinal breaks (OR, 8.07; 95% CI 2.35–27.71), re-detachment (OR, 19.66; 95% CI 4.87–79.38), and retinal detachment area (OR, 12.91; 95% CI 2.34–71.19). Macular pucker was not associated with the surgical technique. Regardless of the surgical technique used, careful observation for postoperative macular pucker is needed after RRD surgery in high-risk cases. These findings can be used to improve the surgical management of patients with RRD. (183 words).

Overexpression of human dynactin‐associated protein isoform a (dynAPa) transforms NIH3T3 cells. DynAPa is a single‐pass transmembrane protein with a carboxy‐terminal region exposed to the outside of cells. According to the NCBI RefSeq database, there may be two other splicing variants of the encoding gene (dynAPb and c). DynAPa and c differ in some amino‐terminal residues (NH2‐MVA in dynAPa and NH2‐MEYQLL in dynAPc). DynAPb has the same amino‐terminal residues as dynAPc, but lacks 55 residues in the intracellular region. All three isoforms have the same carboxy‐terminal region, including the transmembrane domain. Expression of mRNAs of three splicing variants was found in human cancer cell lines ACHN and Caki‐1. The subcellular localization and in vitro cell transformation ability of the three isoforms were examined using NIH3T3 cells overexpressing each respective isoform. All isoforms were found to be localized to the Golgi apparatus and plasma membrane, where the carboxy‐terminal region was exposed to the outside of cells. Cell transformation was tested using focus formation due to loss of contact inhibition of cell proliferation, and colony formation was examined on soft agar and spheroid formation in ultralow U‐bottomed wells. DynAPa robustly formed foci and colonies on soft agar and spheroid, whereas these abilities were considerably decreased for dynAPb and completely lost in dynAPc. These findings warrant dissection studies to identify the dynAP domain that is required for cell transformation.

Abstract Rapid estimation of the coseismic fault model for medium-to-large-sized earthquakes is key for disaster response. To estimate the coseismic fault model for large earthquakes, the Geospatial Information Authority of Japan and Tohoku University have jointly developed a real-time GEONET analysis system for rapid deformation monitoring (REGARD). REGARD can estimate the single rectangular fault model and slip distribution along the assumed plate interface. The single rectangular fault model is useful as a first-order approximation of a medium-to-large earthquake. However, in its estimation, it is difficult to obtain accurate results for model parameters due to the strong effect of initial values. To solve this problem, this study proposes a new method to estimate the coseismic fault model and model uncertainties in real time based on the Bayesian inversion approach using the Markov Chain Monte Carlo (MCMC) method. The MCMC approach is computationally expensive and hyperparameters should be defined in advance via trial and error. The sampling efficiency was improved using a parallel tempering method, and an automatic definition method for hyperparameters was developed for real-time use. The calculation time was within 30 s for 1 × 106 samples using a typical single LINUX server, which can implement real-time analysis, similar to REGARD. The reliability of the developed method was evaluated using data from recent earthquakes (2016 Kumamoto and 2019 Yamagata-Oki earthquakes). Simulations of the earthquakes in the Sea of Japan were also conducted exhaustively. The results showed an advantage over the maximum likelihood approach with a priori information, which has initial value dependence in nonlinear problems. In terms of application to data with a small signal-to-noise ratio, the results suggest the possibility of using several conjugate fault models. There is a tradeoff between the fault area and slip amount, especially for offshore earthquakes, which means that quantification of the uncertainty enables us to evaluate the reliability of the fault model estimation results in real time.

Abstract To report outcomes and risk factors of ultrahypofractionated (UHF) radiotherapy for Japanese prostate cancer patients. This multi-institutional retrospective analysis comprised 259 patients with localized prostate cancer from 6 hospitals. A total dose of 35–36 Gy in 4–5 fractions was prescribed for sequential or alternate-day administration. Biochemical failure was defined according to the Phoenix ASTRO consensus. Toxicities were assessed using National Cancer Institute Common Toxicity Criteria version 4. Tumor control and toxicity rates were analyzed by competing risk frames. Median follow-up duration was 32 months (range 22–97 months). 2- and 3-year biochemical control rates were 97.7% and 96.4%, respectively. Initial prostate-specific antigen (p

Introduction Ductal adenocarcinoma of the prostate is a rare prostate cancer variant and associated with higher stage and greater risk of mortality. Optimal systemic therapy for metastatic ductal adenocarcinoma is not known. Case presentation A 67‐year‐old man presented with ductal adenocarcinoma of the prostate accompanied by multiple lung metastases and advanced bone metastases. We performed channel transurethral resection of the prostate and confirmed the diagnosis of ductal adenocarcinoma of the prostate. DNA sequencing identified a TP53 somatic point mutation (p.Gly245Ser) as the pathogenic variant. Furthermore, a homozygous deletion was observed in mitogen‐activated protein kinase kinase kinase 1. The patient received enzalutamide but deceased 5 months after presenting to our institution. Conclusion To our knowledge, this is the first report of ductal adenocarcinoma of the prostate with a mitogen‐activated protein kinase kinase kinase 1 homozygous deletion. Accumulation of whole‐exome sequencing data is expected to inform future advances in therapy development.

Extensive disease small cell lung cancer (ED‐SCLC) is a systemic disease characterized by diffuse metastases and a poor prognosis. Oligometastatic cases in ED‐SCLC are rare. This study reports the case of a 72‐year‐old Japanese male. A mass lesion was identified on chest computed tomography (CT). Fluorodeoxyglucose‐positron emission tomography/computed tomography (FDG‐PET/CT) revealed a solitary thyroid gland lesion with high FDG uptake as an extrapulmonary finding, suggesting thyroid cancer or a goiter. Upon confirmation of diagnosis, treatment of SCLC was prioritized, and chemoradiotherapy for limited disease SCLC was initiated without further examination of the thyroid gland. The thyroid nodule disappeared after treatment. Two years later, the disease recurred, and a thyroid nodule was found to have reappeared. Upon fine needle aspiration cytology of the thyroid, small cell carcinoma was detected. Therefore, in cases of SCLC, it is necessary to carefully investigate the thyroid for solitary lesions to consider the possibility of oligometastasis. Key points Significant findings of the study Manifesting as a solitary lesion, oligometastasis, particularly in the thyroid, is rare in cases of ED‐SCLC. What this study adds In SCLC cases, it is necessary to carefully investigate the thyroid for solitary lesions to consider the possibility of oligometastasis.

Combinatorial clustering based on the Ising model is drawing attention as a high-quality clustering method. However, conventional Ising-based clustering methods using the Euclidean distance cannot handle irregular data. To overcome this problem, this paper proposes an Ising-based kernel clustering method. The kernel clustering method is designed based on two critical ideas. One is to perform clustering of irregular data by mapping the data onto a high-dimensional feature space by using a kernel trick. The other is the utilization of matrix–matrix calculations in the numerical libraries to accelerate preprocess for annealing. While the conventional Ising-based clustering is not designed to accept the transformed data by the kernel trick, this paper extends the availability of Ising-based clustering to process a distance matrix defined in high-dimensional data space. The proposed method can handle the Gram matrix determined by the kernel method as a high-dimensional distance matrix to handle irregular data. By comparing the proposed Ising-based kernel clustering method with the conventional Euclidean distance-based combinatorial clustering, it is clarified that the quality of the clustering results of the proposed method for irregular data is significantly better than that of the conventional method. Furthermore, the preprocess for annealing by the proposed method using numerical libraries is by a factor of up to 12.4 million × from the conventional naive python’s implementation. Comparisons between Ising-based kernel clustering and kernel K-means reveal that the proposed method has the potential to obtain higher-quality clustering results than the kernel K-means as a representative of the state-of-the-art kernel clustering methods.

Curli fimbriae are amyloids—found in bacteria (Escherichia coli)—that are involved in solid-surface adhesion and bacterial aggregation during biofilm formation. The curli protein CsgA is coded by a csgBAC operon gene, and the transcription factor CsgD is essential to induce its curli protein expression. However, the complete mechanism underlying curli fimbriae formation requires elucidation. Herein, we noted that curli fimbriae formation was inhibited by yccT—i.e., a gene that encodes a periplasmic protein of unknown function regulated by CsgD. Furthermore, curli fimbriae formation was strongly repressed by CsgD overexpression caused by a multicopy plasmid in BW25113—the non-cellulose-producing strain. YccT deficiency prevented these CsgD effects. YccT overexpression led to intracellular YccT accumulation and reduced CsgA expression. These effects were addressed by deleting the N-terminal signal peptide of YccT. Localization, gene expression, and phenotypic analyses revealed that YccT-dependent inhibition of curli fimbriae formation and curli protein expression was mediated by the two-component regulatory system EnvZ/OmpR. Purified YccT inhibited CsgA polymerization; however, no intracytoplasmic interaction between YccT and CsgA was detected. Thus, YccT—renamed CsgI (curli synthesis inhibitor)—is a novel inhibitor of curli fimbriae formation and has a dual role as an OmpR phosphorylation modulator and CsgA polymerization inhibitor.

Cervical elongation in patients with pelvic organ prolapse (POP), who previously underwent laparoscopic sacrocolpopexy (LSC), is not fully understood. We report a case of a second surgery for endometrial cancer complicated with POP recurrence, which seemed to be related to cervical elongation following LSC. A 65-year-old woman was referred for invasive treatment following LSC. Although preoperative endometrial cytology was negative, the resected uterine specimen revealed endometrioid carcinoma. The patient also had complications of cervical prolapse with cystocele Stage III. Repeat surgery was performed with a trachelectomy, anterior-posterior colporrhaphy, and vaginal apex suspension. Mesh had been adequately sutured to the upper cervix in the previous surgery, and the resected cervix was elongated up to 9 cm. Cervical elongation may be correlated with the inaccurate preoperative endometrial examination, and it may also promote POP recurrence leading to a poorly supported pelvic floor. We suggest that cervical elongation should be identified before POP surgery.

Abstract Background The aim of the current study was to evaluate oncologic outcomes of patients who were treated with salvage hysterectomy (HT), compared to systemic chemotherapy (CT) for persistent cervical cancer after definitive radiotherapy (RT)/ concurrent chemoradiotherapy (CCRT). Methods Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005 to 2014 were reviewed retrospectively (n = 317). Those who underwent a HT for persistent cervical cancer after definitive RT/CCRT were matched with propensity scores for patients who underwent systemic CT. Oncologic outcomes between the two groups using a propensity score matched–cohort analysis were compared. Results A total of 142 patients with persistent cervical cancer after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). All background factors between HT and CT groups were well balanced. Median overall survival was 3.8 and 1.5 years in the HT and CT groups, respectively (p = 0.00193, hazards ratio [HR] 0.41, 95% confidence interval [CI] 0.23–0.73), Increasing residual tumor size was significantly associated with a high incomplete resection rate (p = 0.016, Odds Ratio 1.11, 95%CI 1.02–1.22). Severe late adverse events occurred in 7 patients (9.9%) in the HT cohort. Conclusion The current study demonstrated that, when compared to systemic CT, the adoption of salvage HT for patients with persistent cervical cancer after definitive RT/CCRT reduced mortality rate by about 60%. This indicates that salvage HT could be curative treatment for those patients. Further prospective clinical trials with regard to salvage HT after RT/CCRT are warranted.

Abstract While organic batteries have attracted great attention due to their high theoretical capacities, high‐voltage organic active materials (> 4 V vs Li/Li+) remain unexplored. Here, density functional theory calculations are combined with cyclic voltammetry measurements to investigate the electrochemistry of croconic acid (CA) for use as a lithium‐ion battery cathode material in both dimethyl sulfoxide and γ‐butyrolactone (GBL) electrolytes. DFT calculations demonstrate that CA dilitium salt (CA–Li2) has two enolate groups that undergo redox reactions above 4.0 V and a material‐level theoretical energy density of 1949 Wh kg–1 for storing four lithium ions in GBL—exceeding the value of both conventional inorganic and known organic cathode materials. Cyclic‐voltammetry measurements reveal a highly reversible redox reaction by the enolate group at ≈4 V in both electrolytes. Battery‐performance tests of CA as lithium‐ion battery cathode in GBL show two discharge voltage plateaus at 3.9 and 3.1 V, and a discharge capacity of 102.2 mAh g–1 with no capacity loss after five cycles. With the higher discharge voltages compared to the known, state‐of‐the‐art organic small molecules, CA promises to be a prime cathode‐material candidate for future high‐energy‐density lithium‐ion organic batteries.

Vulvar proximal-type epithelioid sarcoma during pregnancy is extremely rare; only two reports are available to date. Herein, we describe a 36-year-old woman who presented with a pigeon-egg-sized solid mass with cystic component on the left labia majora at 18 weeks of gestation. The patient underwent tumor resection at 23 weeks of gestation and was diagnosed with epithelioid sarcoma, proximal-type. At 29 weeks of gestation, elective cesarean section, radical local resection of the vulva and vagina, and inguinal lymphadenectomy were performed. After surgery, she underwent six courses of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cisplatin 50 mg/m2) every four weeks. The patient and her baby survived with neither recurrence nor complications until 5 years. Aggressive management for proximal-type epithelioid sarcoma, such as early termination of pregnancy and operation, can improve maternal outcomes.

Abstract Background Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. Methods Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. Results A total of 49 FFPE and LBC specimens (n = 24) were analyzed, revealing characteristic mutations for endometrial cancer, including PTEN, CTNNB1, PIK3CA, and PIK3R1 mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. Conclusion These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.

Abstract Introductions When tumor tissue samples are unavailable to search for actionable driver mutations, archival cytology samples can be useful. We investigate whether archival cytology samples can yield reliable genomic information compared to corresponding formalin‐fixed paraffin‐embedded (FFPE) tumor samples. Patients and Methods Pretreatment class V archival cytology samples with adequate tumor cells were selected from 172 lung cancer patients. The genomic profiles of the primary lung tumors have been analyzed through whole‐exome regions of 53 genes. We compared the genomic profiles based on the oncogenicity and variant allele frequency (VAF) between the archival cytology and the corresponding primary tumors. We also analyzed the genomic profiles of serial cytological samples during the treatment of EGFR‐TKI. Results A total of 43 patients were analyzed with the paired samples for DNA mutations and other three patients were analyzed for their fusion genes. A total of 672 mutations were detected. Of those, 106 mutations (15.8%) were shared with both samples. Sixty of seventy‐seven (77.9%) shared mutations were oncogenic or likely oncogenic mutations with VAF ≧10%. As high as 90% (9/10) actionable driver mutations and ALK and ROS1 fusion genes were successfully detected from archival cytology samples. Sequential analysis revealed the dynamic changes in EGFR‐TKI‐resistant mutation (EGFR p.T790M) during the course of treatment. Conclusion Archival cytology sample with adequate tumor cells can yield genetic information compared to the primary tumors. If tumor tissue samples are unavailable, we can use archival cytology samples to search for actionable driver mutations.

Background and aimsImmune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach.MethodsIn this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed.ResultsTwo-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group.ConclusionsPatients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.

MoS2 structures with large surface areas and edges for use as electrocatalysts in the hydrogen evolution reaction (HER) are typically synthesized via solvothermal and hydrothermal methods. However, to utilize the fabricated particles as electrodes, they should be applied on substrates in the form of inks; this requires additional processing. Furthermore, if the electrode has a three-dimensional structure with more than two sides, applying the ink to the entire surface is difficult. Therefore, there is a requirement for a thin-film deposition process based on a fast reaction that does not require toxic substances and can be used for one-pot electrode fabrication. In this study, we present a rapid, one-step hydrothermal electrodeposition technique for the formation of MoS2 thin films on glassy carbon substrates. The MoS2 electrocatalysts fabricated using this method have surfaces that are rich in metallic phases, and they exhibit good activity as hydrogen evolution catalysts. This hydrothermal electrodeposition technique is expected to be broadly applicable to various electrodes and other technologies.

Objectives Vasohibin-1 (VASH1) is an endogenous angiogenesis regulator expressed in activated vascular endothelial cells. We previously reported that high VASH1 expression is a predictor of progression in acinar adenocarcinoma of the prostate. In this study, we evaluated the characteristics of ductal adenocarcinoma of the prostate by comparing the level of VASH1 expression between ductal and acinar adenocarcinoma specimens.Design and setting A retrospective cohort study at two centres in Japan.Participants Among the 1495 patients who underwent radical prostatectomy or transurethral resection for the past 15 years, a total of 14 patients diagnosed with ductal adenocarcinoma and 20 patients diagnosed with acinar adenocarcinoma with a Gleason score of 4+4 were included.Interventions We immunohistochemically examined the CD34 expression as the microvessel density (MVD) and activated endothelial cells as the VASH1 density (vessels per mm2).Primary and secondary outcome measures The primary outcome was the association of MVD and VASH1 density between ductal and acinar adenocarcinoma, and the secondary outcome was their oncological outcomes.Results Nine patients (64.3%) with ductal adenocarcinoma were diagnosed at an advanced clinical stage, and five patients (35.7%) died from cancer during a median follow-up of 56.0 months. The VASH1 densities (mean±SD) in ductal and acinar adenocarcinoma were 45.1±18.5 vs 16.1±21.0 (p

Ancient dental calculus, formed from dental plaque, is a rich source of ancient DNA and can provide information regarding the food and oral microbiology at that time. Genomic analysis of dental calculus from Neanderthals has revealed the difference in bacterial composition of oral microbiome between Neanderthals and modern humans. There are few reports investigating whether the pathogenic bacteria of periodontitis, a polymicrobial disease induced in response to the accumulation of dental plaque, were different between ancient and modern humans. This study aimed to compare the bacterial composition of the oral microbiome in ancient and modern human samples and to investigate whether lifestyle differences depending on the era have altered the bacterial composition of the oral microbiome and the causative bacteria of periodontitis. Additionally, we introduce a novel diagnostic approach for periodontitis in ancient skeletons using micro-computed tomography. Ancient 16S rDNA sequences were obtained from 12 samples at the Unko-in site (18th-19th century) of the Edo era (1603–1867), a characteristic period in Japan when immigrants were not accepted. Furthermore, modern 16S rDNA data from 53 samples were obtained from a database to compare the modern and ancient microbiome. The microbial co-occurrence network was analyzed based on 16S rDNA read abundance. Eubacterium species, Mollicutes species, and Treponema socranskii were the core species in the Edo co-occurrence network. The co-occurrence relationship between Actinomyces oricola and Eggerthella lenta appeared to have played a key role in causing periodontitis in the Edo era. However, Porphyromonas gingivalis, Fusobacterium nucleatum subsp. vincentii, and Prevotella pleuritidis were the core and highly abundant species in the co-occurrence network of modern samples. These results suggest the possibility of differences in the pathogens causing periodontitis during different eras in history.

Profit sharing (PS) is well known as a kind of reinforcement learning. In a PS method, a reward is generally distributed with a geometrically decreasing function, and the common ratio of the function is called a discount rate. A large discount rate increases the learning speed, but a non-optimal policy may be learned. On the other hand, a small discount rate improves the performance of the policy, but the learning may not proceed smoothly because of the shallow learning depth. In this paper, in order to cope with these problems, we propose a method that reinforces both the detour path and the non-detour path with different discount rates. Finally, this method is applied to a maze problem and an altruistic multi-agent environment to confirm its effectiveness.

Abstract The source rupture process of the 2018 Hokkaido Eastern Iburi earthquake was investigated by performing a joint inversion analysis using the strong motion and geodetic data. A fault model that consists of two fault planes was constructed by considering the relocated aftershock distribution and the focal mechanisms. The inversion result showed that the large slip occurred at approximately 22 km depth, which was much shallower than the hypocentral depth. Our results showed that the rupture initiated on the minor fault plane around the hypocenter and the major fault plane started to rupture 4–6 s after the rupture initiation. Although the shape of the minor fault plane has not been clearly determined, the major fault plane appears to be high-angle, east-dipping. An additional inversion with only the major fault plane showed that the strong ground motion near the source was mainly generated from the major fault plane. The total seismic moment estimated by the inversion with the two fault-plane model was 1.1 × 1019 Nm, which yielded an M w of 6.6. Using the inversion result of the two fault-plane model, we simulated the ground surface and borehole waveforms at strong motion station IBUH03 where the large velocity pulse was observed on the ground surface. The simulations suggest that this large velocity pulse was generated from the combination of the large slip of the source and large site amplification of the velocity structure between the ground surface and borehole seismometers.

For practical room-temperature magnesium rechargeable battery operation, utilizing the nano-sized MgMn2O4 spinel as cathode material is effective way to have high rate-capabilities; however, electrolyte decomposition at the cathode/electrolyte interface is inevitable. In this work, a Mg-Fe binary oxide is coated onto nano-sized MgMn2O4 to form stable cathode electrolyte interface (CEI). This developed cathode material suppresses the electrolyte decomposition and improves the cyclability at room temperature.

Oxidative stress is considered to be involved in the pathogenesis of primary blast-related traumatic brain injury (bTBI). We evaluated the effects of ascorbic acid 2-glucoside (AA2G), a well-known antioxidant, to control oxidative stress in rat brain exposed to laser-induced shock waves (LISWs). The design consisted of a controlled animal study using male 10-week-old Sprague-Dawley rats. The study was conducted at the University research laboratory. Low-impulse (54 Pa•s) LISWs were transcranially applied to rat brain. Rats were randomized to control group (anesthesia and head shaving, n = 10), LISW group (anesthesia, head shaving and LISW application, n = 10) or LISW + post AA2G group (AA2G administration after LISW application, n = 10) in the first study. In another study, rats were randomized to control group (n = 10), LISW group (n = 10) or LISW + pre and post AA2G group (AA2G administration before and after LISW application, n = 10). The measured outcomes were as follows: (i) motor function assessed by accelerating rotarod test; (ii) levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker; (iii) ascorbic acid in each group of rats. Ascorbic acid levels were significantly decreased and 8-OHdG levels were significantly increased in the cerebellum of the LISW group. Motor coordination disorder was also observed in the group. Prophylactic AA2G administration significantly increased the ascorbic acid levels, reduced oxidative stress and mitigated the motor dysfunction. In contrast, the effects of therapeutic AA2G administration alone were limited. The results suggest that the prophylactic administration of ascorbic acid can reduce shock wave-related oxidative stress and prevented motor dysfunction in rats.

OBJECTIVE:Interleukin (IL)-17A and IL-18 have been proposed to play important roles in periodontitis and type 2 diabetes mellitus (DM), but human data are conflicting. The present study aimed to investigate the roles of IL-17A and IL-18 in periodontitis and DM by measuring salivary and serum levels, respectively. MATERIALS AND METHODS:A total of 49 participants with type 2 DM and 25 control subjects without type 2 DM were recruited. A periodontal screening and recording (PSR) index (0, 1-2, 3, and 4) was used to classify whether these subjects had periodontitis. Salivary and serum IL-17A and IL-18 levels were measured by enzyme-linked immunosorbent assay. Multiple linear regression analyses were used to evaluate the associations between these cytokines and clinical parameters. RESULTS:Salivary IL-17A levels were not significantly different between patients with DM and controls, however, the levels were significantly higher in controls with periodontitis than those without periodontitis (p = 0.031). Salivary IL-17A levels were significantly associated with the PSR index (β = 0.369, p = 0.011). Multiple linear regression analyses revealed the association of salivary IL-18 levels and fasting plasma glucose (β = 0.270, p = 0.022) whereas serum IL-18 levels were associated with HbA1C (β = 0.293, p = 0.017). No correlation between salivary and serum levels of IL-17A and IL-18 was found. CONCLUSION:Salivary IL-17A was strongly associated with periodontitis, whereas salivary IL-18 was associated with FPG and serum IL-18 was associated with HbA1C. These results suggest the role of these cytokines in periodontal inflammation and DM.

A 60-year-old man with a history of smoking was transferred to our hospital for consciousness disorder. A diagnosis of ALK-rearranged lung adenocarcinoma associated with a paraneoplastic electrolytic disorder was made following a cutaneous needle biopsy. Both the primary lung lesion and multiple metastases shrunk and his electrolytic disorder resolved after the introduction of a first-line molecular-targeted drug chemotherapy with crizotinib. We herein report a case of ALK-rearranged lung adenocarcinoma accompanied by SIADH, successfully treated with crizotinib.