Search

Abstract Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Introduction Neuroendocrine prostate cancer has a poor prognosis. Although disseminated intravascular coagulation associated with malignancy can be lethal, it very rarely occurs among patients with primary neuroendocrine prostate cancer. Case presentation An 80‐year‐old man presented to our hospital with bloody sputum. Blood examination indicated disseminated intravascular coagulation. Serum levels of prostate‐specific antigen and neuron‐specific enolase were 44.274 and 176 ng/mL, respectively. Core needle biopsies of an irregular mass in the prostate and a metastatic tumor in the left iliac bone showed similar neuroendocrine carcinoma cells. Hence, the patient was diagnosed with disseminated intravascular coagulation associated with primary and metastatic neuroendocrine prostate cancer. Unfortunately, he passed away 3 weeks after the biopsies. Conclusion Given the difficulty of effectively treating metastatic neuroendocrine prostate cancer among patients in poor physical condition due to disease progression, identifying a new well‐tolerated treatment modality is imperative.

Abstract IgG4-related mastitis is an extremely rare IgG4-related sclerosing disease involving the breast that must be differentiated from breast cancer. There is currently no consensus regarding the optimal treatment strategies. Here, we report a case of IgG4-related mastitis followed up without excision or steroid therapy. Although the association between IgG4-related mastitis and breast cancer remains unclear, regular follow-up imaging and measurement of serum concentrations of disease activity markers may allow for follow-up without excision or steroid therapy.

Besides the fission–fusion dynamics, the cellular distribution of mitochondria has recently emerged as a critical biological parameter in regulating mitochondrial function and cell survival. We previously found that mitochondrial clustering on the nuclear periphery, or monopolar perinuclear mitochondrial clustering (MPMC), accompanies the anticancer activity of air plasma-activated medium (APAM) against glioblastoma and human squamous cell carcinoma, which is closely associated with oxidant-dependent tubulin remodeling and mitochondrial fragmentation. Accordingly, this study investigated the regulatory roles of nitric oxide (NO) in the anticancer activity of APAM. Time-lapse analysis revealed a time-dependent increase in NO accompanied by MPMC. In contrast, APAM caused minimal increases in MPMC and NO levels in nontransformed cells. NO, hydroxyl radicals, and lipid peroxide levels increased near the damaged nuclear periphery, possibly within mitochondria. NO scavenging prevented tubulin remodeling, MPMC, perinuclear oxidant production, nuclear damage, and cell death. Conversely, synthetic NO donors augmented all the prodeath events and acted synergistically with APAM. Salinomycin, an emerging drug against multidrug-resistant cancers, had similar NO-dependent effects. These results suggest that APAM and salinomycin induce NO-dependent cell death, where MPMC and oxidative mitochondria play critical roles. Our findings encourage further investigations on MPMC as a potential target for NO-driven anticancer agents against drug-resistant cancers.

Obesity and ageing are the most important risk factors for sleep apnoea syndrome (SAS); however, the role of body mass index (BMI) on sleep status in healthy older adults is unclear. To explore sleep parameters according to BMI among active older adults, we cross-sectionally examined the relationship between sleep-related parameters and BMI in 32 Japanese adults aged from 83 to 95 years without long-term care who were unaware of having SAS. Correlation and linear regression analyses were performed. Moderate or severe SAS prevalence was high in both those with low (68.8%) and high (68.8%) BMI. A higher increase in apnoea-hypopnoea index (AHI) was negatively correlated with sleep depth in the high-BMI group. In the low-BMI group, the number of awakenings and age were positively correlated with AHI. Older adults may have SAS regardless of their BMI, and the sleep status of patients with SAS may vary by BMI.

A 50-year-old Japanese man with enlargement of the right scrotum was presented to our hospital. Preoperative examination confirmed a multilocular cyst with septa attached to the testis. Radical orchiectomy was performed. Pathological examination revealed closely-located two cysts; larger one was infected hydrocele testis, and smaller one was epithelial cyst, which were immunohistochemically positive widely for estrogen receptor (ER) and partly for progesterone receptor (PR). We concluded that the smaller cyst was serous cystadenoma of the epididymis.

Abstract Analog hardware-based training provides a promising solution to developing state-of-the-art power-hungry artificial intelligence models. Non-volatile memory hardware such as resistive random access memory (RRAM) has the potential to provide a low power alternative. The training accuracy of analog hardware depends on RRAM switching properties including the number of discrete conductance states and conductance variability. Furthermore, the overall power consumption of the system inversely correlates with the RRAM devices conductance. To study material dependence of these properties, TaOx and HfOx RRAM devices in one-transistor one-RRAM configuration (1T1R) were fabricated using a custom 65 nm CMOS fabrication process. Analog switching performance was studied with a range of initial forming compliance current (200–500 µA) and analog switching tests with ultra-short pulse width (300 ps) was carried out. We report that by utilizing low current during electroforming and high compliance current during analog switching, a large number of RRAM conductance states can be achieved while maintaining low conductance state. While both TaOx and HfOx could be switched to more than 20 distinct states, TaOx devices exhibited 10× lower conductance, which reduces total power consumption for array-level operations. Furthermore, we adopted an analog, fully in-memory training algorithm for system-level training accuracy benchmarking and showed that implementing TaOx 1T1R cells could yield an accuracy of up to 96.4% compared to 97% for the floating-point arithmetic baseline, while implementing HfOx devices would yield a maximum accuracy of 90.5%. Our experimental work and benchmarking approach paves the path for future materials engineering in analog-AI hardware for a low-power environment training.

Both Leydig cell tumor (LCT), which is a sex cord-stromal tumor, and spermatocytic tumor (ST), which is a germ cell tumor, are rare testicular tumors. Synchronous LCT and ST in the unilateral testis are extremely rare because of their different origins. Herein, we report the case of an 84-year-old male patient with right scrotal swelling due to a testicular tumor. His age was out of the onset peak age of LCT but within ST. To the best of our knowledge, this is the first case with synchronous LCT and ST in the unilateral testis.

Analog memory presents a promising solution in the face of the growing demand for energy-efficient artificial intelligence (AI) at the edge. In this study, we demonstrate efficient deep neural network transfer learning utilizing hardware and algorithm co-optimization in an analog resistive random-access memory (ReRAM) array. For the first time, we illustrate that in open-loop deep neural network (DNN) transfer learning for image classification tasks, convergence rates can be accelerated by approximately 3.5 times through the utilization of co-optimized analog ReRAM hardware and the hardware-aware Tiki-Taka v2 (TTv2) algorithm. A simulation based on statistical 14 nm CMOS ReRAM array data provides insights into the performance of transfer learning on larger network workloads, exhibiting notable improvement over conventional training with random initialization. This study shows that analog DNN transfer learning using an optimized ReRAM array can achieve faster convergence with a smaller dataset compared to training from scratch, thus augmenting AI capability at the edge.

Bladder cancer commonly metastasizes to the lymph nodes. Rectal obstruction (RO) caused by bladder cancer has been reported rarely, and its underlying mechanism remains unclear. Herein, we present an autopsy case of a 67-year-old man with RO caused by urothelial carcinoma (UC) with a micropapillary variant in the bladder. The autopsy showed high-grade UC infiltrating the rectum via the bladder's lateral pedicle, and widely spreading within the retroperitoneum due to lymphatic dissemination. Given that RO caused by bladder cancer is typically diagnosed after it has become a systemic disease, it is crucial to consider systemic treatment for the patient.

Abstract Dielectric breakdown (BD) is known to cause component failure in electronic devices and high‐voltage power lines over many decades. In recent years, this failure mechanism has been exploited to intentionally form nanoscale filaments in resistive random‐access‐memory (ReRAM) devices for artificial intelligence (AI). The statistical nature of this failure mechanism, known as the inverse size scaling law based on the weakest‐link theory, dictates the ever‐higher forming voltages for ReRAM devices, in turn, requiring additional peripheral transistors. This law also causes diminishing lifetimes of electronic components for future generations of very‐large‐integrated circuits (VLSI) technology. Currently, the semiconductor industry faces these scaling barriers limiting the miniaturization of both VLSI and AI hardware technology. Here, experimental evidence of a reverse area dependence is presented by introducing an innovative fabrication process with a hydrogen‐plasma‐treated layer in a bilayer HfO2 structure. Using joint order statistics rather than traditional extreme‐value statistics, a physics‐based statistical model is developed in agreement with the experimental data, thus demonstrating that there is no fundamental reason preventing this law from being reversed or altered. These findings will have a significant impact on both technology scaling and fabrication innovation for electronic and/or bioinspired nanomaterials; moreover, stimulate much research in physics, statistics, and reliability.

For engines operating using heavy fuel oil (HFO), the nozzle rings of turbocharger turbines are prone to severe degradation because of contamination with unburned fuel deposits. This contamination may lead to increased excitation of blade resonance. A previous study provides technical guidelines on how to extract the relevant information from pulsation spectra using a single probe installed away from the turbine trailing edge and some sound experimental proofs of integral mode turbine vibration detection. These theoretical discussions only allude to the effects of mistuning and interferences due to classical blade passing frequencies on sound radiation patterns emitted by integral blade vibration modes. In this study, both effects are thoroughly discussed. Combining the knowledge of theoretical study and further experimental results, the application range of this blade vibration detection method can be remarkably extended.

Abstract Although vaccination may precipitate relapses of nephrotic syndrome (NS) in children with idiopathic NS, no data are available regarding NS activity regarding influenza (flu) virus infections and NS relapses after receiving inactivated flu vaccines. We conducted a nationwide study of children aged 6 months to 15 years with idiopathic NS to assess the relationship between NS relapse, flu vaccination, and flu infections. We used a multivariate Poisson regression model (MPRM) to calculate the risk ratio (RR) for flu infection and for NS relapse in children with and without flu vaccination. Data of 306 children were assessed. The MPRM in all 306 children showed a significantly lower RR for flu infection (RR: 0.21, 95% confidence interval CI 0.11–0.38) and for NS relapse (RR: 0.22, 95% CI 0.14–0.35) in children receiving flu vaccination compared with unvaccinated children. In an additional MPRM only among 102 children receiving flu vaccination, they had a significantly lower risk for NS relapse during the post-vaccination period (RR: 0.31. 95% CI 017–0.56) compared with the pre-vaccination period. Although our study was observational, based on the favorable results of flu vaccinations regarding flu infections and NS relapse, the vaccine may be recommended for children with NS.

We demonstrate a modified stochastic gradient (Tiki-Taka v2 or TTv2) algorithm for deep learning network training in a cross-bar array architecture based on ReRAM cells. There have been limited discussions on cross-bar arrays for training applications due to the challenges in the switching behavior of nonvolatile memory materials. TTv2 algorithm is known to overcome the device non-idealities for deep learning training. We demonstrate the feasibility of the algorithm for a linear regression task using 1R and 1T1R ReRAM devices. Using the measured device properties, we project the performance of a long short-term memory (LSTM) network with 78 K parameters. We show that TTv2 algorithm relaxes the criteria for symmetric device update response. In addition, further optimization of the algorithm increases noise robustness and significantly reduces the required number of states, thereby drastically improving the model accuracy even with non-ideal devices and achieving the test error close to that of the conventional learning algorithm with an ideal device.

Study Objectives: Aging is a risk factor for sleep apnoea syndrome (SAS), which is associated with lower quality of life and sudden mortality. However, SAS is often overlooked in older adults without suspicions. Therefore, this study aimed to evaluate SAS incidence and 48 other general factors in older adults.Methods: This cross-sectional study included all non-caregiver-certified, healthy individuals (N = 32) who survived during the long-term cohort study and agreed to participate in apnoea-hypopnoea index (AHI) measurement (aged 83–95 years). AHI and 48 other general factors were evaluated, and simple linear regression analysis was used to identify potential AHI-related factors. Stepwise evaluation was further performed using multiple linear regression analyses.Results: Although no individuals were previously diagnosed with SAS, 30 (93.75%) participants had some degree of SAS (AHI > 5/h), and 22 (68.75%) had severe or moderate SAS (AHI > 15/h). Compared with typical single risk factors represented by body mass index, combining daily steps and other factors improved the fit to the multiple linear regression. Combining daily steps and body mass index improved the fit for males and combining daily steps and red blood cell count improved the fit for females.Conclusion: SAS was highly prevalent in unaware healthy Japanese older adults; combinations of daily steps and body mass index, and daily steps and red blood cell count may predict AHI in such individuals without the need for a specific AHI test.

The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α‐synuclein into filaments is believed to underlie the prion‐like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α‐synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human α‐synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of the seeds. Identification of these factors will be essential for understanding the prion‐like spreading of α‐synuclein proteinopathies.

Abstract ETS homologous factor (EHF) belongs to the epithelium-specific subfamily of the E26 transformation-specific (ETS) transcription factor family. Currently, little is known about EHF’s function in cancer. We previously reported that ETS1 induces expression of the ZEB family proteins ZEB1/δEF1 and ZEB2/SIP1, which are key regulators of the epithelial–mesenchymal transition (EMT), by activating the ZEB1 promoters. We have found that EHF gene produces two transcript variants, namely a long form variant that includes exon 1 (EHF-LF) and a short form variant that excludes exon 1 (EHF-SF). Only EHF-SF abrogates ETS1-mediated activation of the ZEB1 promoter by promoting degradation of ETS1 proteins, thereby inhibiting the EMT phenotypes of cancer cells. Most importantly, we identified a novel point mutation within the conserved ETS domain of EHF, and found that EHF mutations abolish its original function while causing the EHF protein to act as a potential dominant negative, thereby enhancing metastasis in vivo. Therefore, we suggest that EHF acts as an anti-EMT factor by inhibiting the expression of ZEBs, and that EHF mutations exacerbate cancer progression.

Negative capacitance field effect transistors (NCFETs) are modeled in this study, with an emphasis on junction design, implications of complementary logic, and device $V_{t}$ menu enablement. Contrary to conventional MOSFET design, increased junction overlap is beneficial to NCFETs, provided the remnant polarization ( $P_{r}$ ) is high enough. Combining broad junctions with complementary capacitance matching (CCM) in MFMIS (metal/ferroelectric/metal/insulator/semiconductor) NCFETs, it is shown that super-steep and non-hysteretic switching are not mutually exclusive, and that it is theoretically possible to achieve non-hysteretic sub-5 mV/dec SS over >6 decades. In a CMOS circuit, due to CCM, low- $V_{t}$ pairs provide steeper subthreshold swing (SS) than high- $V_{t}$ pairs. Transient power/performance is also modeled, and it is shown that a DC-optimal NCFET design, employing broad junctions, CCM, and a low- $V_{t}$ NFET/PFET pair, does not translate to improved AC power/performance in unloaded circuits compared to a conventional FET reference. It is also shown that the same non-hysteretic DC design point is hysteretic in AC and may also lead to full polarization switching at higher voltages. Thus, a usable voltage window for AC NCFET operation forces a retreat from the DC-optimal design point.

Transurethral double J (DJ) stent placement is a standard method for drainage during ureteral obstruction caused by a ureteral stone and for the management of complications after transurethral ureterolithotripsy (TUL). This is a safe and minimally invasive technique; however, severe cases of DJ stent migration have been reported, although rarely. Herein, we report the CASE of a 48-year-old man with DJ stent migration as renal penetration, which arose as a complication after an unsuccessful TUL. As transurethral DJ stent placement is one of the basic techniques performed by urologists, possible rare complications of the placement should be taken into consideration.

Objectives: The correlations of the ratio of long-/short-chain DNA fragments in blood with the existence of cancer and the clinicopathological features of colorectal cancer (CRC) were examined. The potential use of this ratio for diagnostic screening was evaluated. Methods: DNA concentrations were amplified using Alu247 for long-chain DNA fragments and Alu115 for long- and short-chain DNA fragments. The Alu247/115 ratio was calculated for 60 patients with CRC and 24 healthy volunteers. The correlation of the Alu247/115 ratio with clinicopathological variables and the efficacy of this ratio as a tumor marker were examined. The Alu247/115 ratio cut-off value was set using a receiver operating characteristic (ROC) curve. Results: The Alu247/115 ratio was significantly higher in patients with CRC than in healthy volunteers (P

Non-thermal atmospheric pressure plasma (NTAPP)-activated liquids have emerged as new promising anticancer agents because they preferentially injure malignant cells. Here, we report plasma-activated infusion (PAI) as a novel NTAPP-based anti-neoplastic agent. PAI was prepared by irradiating helium NTAP to form a clinically approved infusion fluid. PAI dose-dependently killed malignant melanoma and osteosarcoma cell lines while showing much lower cytotoxic effects on dermal and lung fibroblasts. We found that PAI and salinomycin (Sal), an emerging anticancer stem cell agent, mutually operated as adjuvants. The combined administration of PAI and Sal was much more effective than single-agent application in reducing the growth and lung metastasis of osteosarcoma allografts with minimal adverse effects. Mechanistically, PAI explicitly induced necroptosis and increased the phosphorylation of receptor-interacting protein 1/3 rapidly and transiently. PAI also suppressed the ambient autophagic flux by activating the mammalian target of the rapamycin pathway. PAI increased the phosphorylation of Raptor, Rictor, and p70-S6 kinase, along with decreased LC3-I/II expression. In contrast, Sal promoted autophagy. Moreover, Sal exacerbated the mitochondrial network collapse caused by PAI, resulting in aberrant clustering of fragmented mitochondrial in a tumor-specific manner. Our findings suggest that combined administration of PAI and Sal is a promising approach for treating these apoptosis-resistant cancers.

Pancreatic metastasis from prostate cancer (PC) is quite rare. Herein, we report the case of a 67-year-old man with pancreatic metastasis from a neuroendocrine differentiated PC (NEDPC), a local recurrence after radical prostatectomy and androgen deprivation therapy for 6 years. Chemoradiotherapy was initiated for the locally recurrent NEDPC, and it had almost disappeared after the therapy. However, rapidly enlarged pancreatic metastasis from the NEDPC was detected 6 months after therapy. There is no standard treatment available for pancreatic metastasis from NEDPC owing to its rarity; hence, further knowledge and clinical experience regarding it are crucial.

Tomatoes require higher irradiance, although the incidence of physiological disorders in fruit increases at high temperatures. Near-infrared (800–2500 nm) (NIR) reflective materials are effective tools to suppress rising air temperatures in greenhouses. We examined the physiological and morphological changes in tomato growth and fruit quality when grown in a high tunnel covered with NIR reflective film (NR) and in another covered with polyolefin film (PO; control). There was no relationship between the fruit cracking rate and mean daytime temperature under NR. The fruit temperature at the same truss was lower and the increase in air temperature was slow under NR. Fruit dry matter (DM) content under NR was also significantly decreased. These findings suggest that the reduction in fruit cracking under NR results from a decrease in fruit DM content as a consequence of lower fruit temperature and a decrease in total DM (TDM). Total fruit yield did not differ, whereas TDM was significantly decreased under NR. This was considered to result from a lower transmitted photosynthetic photon flux density (400–700 nm) (PPFD) and LAI, and lower photosynthetic capacity in single leaves because of a decrease in both total nitrogen and chlorophyll content. We conclude that NR film reduces fruit cracking in exchange for a slight reduction in TDM.

Abstract Background In Japan, several large healthcare databases have become available for research since the early 2000’s. However, validation studies to examine the accuracy of these databases remain scarce. We conducted a validation study in order to estimate the positive predictive value (PPV) of local or ICD-10 codes for acute myocardial infarction (AMI) in Japanese claims. In particular, we examined whether the PPV differs between claims in the Diagnosis Procedure Combination case mix scheme (DPC claims) and in non-DPC claims. Methods We selected a random sample of 200 patients from all patients hospitalized at a large tertiary-care university hospital between January 1, 2009 and December 31, 2011 who had an inpatient claim assigned a local or ICD-10 code for AMI. We used a standardized data abstraction form to collect the relevant information from an electronic medical records system. Abstracted information was then categorized by a single cardiologist as being either definite or not having AMI. Results In a random sample of 200 patients, the average age was 67.7 years and the proportion of males was 78.0%. The PPV of the local or ICD-10 code for AMI was 82.5% in this sample of 200 patients. Further, of 178 patients who had an ICD-10 code for AMI based on any of the 7 types of condition codes in the DPC claims, the PPV was 89.3%, whereas of the 161 patients who had an ICD-10 code for AMI based on any of 3 major types of condition codes in the DPC claims, the PPV was 93.8%. Conclusion The PPV of the local or ICD-10 code for AMI was high for inpatient claims in Japan. The PPV was even higher for the ICD-10 code for AMI for those patients who received AMI care through the DPC case mix scheme. The current study was conducted in a single center, suggesting that a multi-center study involving different types of hospitals is needed in the future. The accuracy of condition codes for DPC claims in Japan may also be worth examining for conditions other than AMI such as stroke.

Abstract Background Clostridium ramosum is a generally non-pathogenic enteric anaerobe, and Fournier’s gangrene is a rare necrotizing soft tissue infection with male predisposition affecting the perineum and the genital area. We report, to our knowledge, the first case of Fournier’s gangrene caused by C. ramosum in a female patient with multiple underlying conditions. Case presentation A 44-year-old woman with a 6-year history of insulin-dependent diabetes mellitus after total pancreatectomy and an 11-year history of central diabetes insipidus developed a pain in the genital area after a month of urinary catheter use. The lower abdominal pain worsened gradually over 2 weeks, and the pain, general fatigue, and loss of appetite prompted the patient’s hospital admission. As she had severe edema in her pelvic and bilateral femoral areas, ceftriaxone was started empirically after collecting two sets of blood cultures. On hospital day 2, CT examination revealed the presence of necrotizing faciitis in the genital and pelvic areas, and the antibiotics were changed to a combination of meropenem, vancomycin, and clindamycin. Gram-positive cocci and gram-positive rods were isolated from blood cultures, which were finally identified as Streptococcus constellatus and C. ramosum using superoxide dismutase and 16S rDNA sequencing. An emergent surgery was performed on hospital day 2 to remove the affected tissue. Despite undergoing debridement and receiving combined antimicrobial chemotherapies, the patient’s clinical improvement remained limited. The patient’s condition continued to deteriorate, and she eventually died on hospital day 8. In the present case, the underlying diabetes mellitus, urinary incontinence due to central diabetes insipidus, undernutrition, and edema served as the predisposing conditions. Conclusions C. ramosum is a potentially opportunistic pathogen among immunosuppressed persons and a rare cause of necrotizing fasciitis.

In this paper, we propose the extendibility of ultra-thin body and box (UTBB) devices to 7 and 5 nm technology nodes focusing on electrostatics. A difficulty in scaling traditional UTBB is the need for SOI scaling to about one fourth of the gate length. We propose a U-channel fully depleted silicon on insulator architecture that starts off with a thicker SOI (8-11 nm) and has a U-shaped channel enabled by a recessed metal gate. This device improves the electrostatics by increasing the overall gate length at fixed metal gate opening, mitigating drain field coupling to the source due to the recessed metal gate region and having thin SOI below the center of the device (4-5 nm). Modeling shows that good electrostatics can be maintained at small metal gate opening to enable pitch scaling. This device provides lower cost options for mobile and IOT technologies.

Background/Aims: Hemodialysis patients have poor prognosis due to increased prevalence of cardiovascular diseases. Treatment to suppress increases in sympathetic nerve activity and QT prolongation may have the potential to reduce the occurrence of these events. The L/N-type Calcium (Ca) channel blocker cilnidipine has unique inhibitory action to inhibit sympathetic nerve activity and in a canine model ameliorates QT prolongation. In this study, we investigated whether cilnidipine has inhibitory effects on heart rate, an index of sympathetic nerve activity, and QT prolongation in patients undergoing dialysis. Methods: An L-type Ca channel blocker amlodipine was administered for 4 weeks followed by cilnidipine treatment for 4 weeks. On the last day of each period, heart rate and corrected QT interval were estimated and compared between the two periods. Results: Cilnidipine showed greater suppression of heart rate during dialysis than did amlodipine. The corrected QT interval in one dialysis session was significantly increased, and 3 of 17 patients showed prominent QT prolongation during administration of amlodipine but not cilnidipine. Conclusion: These data suggested that cilnidipine may inhibit increases in heart rate and QT interval. Cilnidipine may have beneficial effects in reducing cardiovascular events, resulting from increased sympathetic nerve activity and lethal arrhythmias in hemodialysis patients.

Late-onset rectal bleeding after transrectal prostate needle biopsy is potentially life-threatening. We report the case of a 75-year-old male who presented with severe rectal bleeding 3 days after transrectal prostate needle biopsy. Because the bleeding could not be arrested by conservative treatment, emergent colorectal endoscopic clipping (twice) and elective angiography were performed. Packed red blood cell transfusion (14 units in total) was required to treat the developed hemorrhagic shock. Colorectal endoscopy and arterial embolization are effective treatments for severe rectal bleeding after transrectal prostate needle biopsy and should be performed without hesitation. Keywords: Arterial bleeding, Hemorrhagic shock, Prostate biopsy, Rectal bleeding

Duodenal and rectal obstructions due to urological malignancies are relatively uncommon. We report an autopsy case of an 83-year-old man with a history of renal pelvic cancer who presented these obstructions. Autopsy revealed that urothelial cancer infiltrated the bladder wall, duodenal wall, rectal wall, and prostate and widely spread in the retroperitoneal lymphatic vessel. We concluded that renal pelvic cancer recurred in the bladder wall and then infiltrated into each organ because of lymphatic dissemination. The gastrointestinal obstructions due to urinary tract cancer were lethal. Further knowledge and clinical experience regarding these types of obstructions are crucial. Keywords: Duodenal obstruction, Lymphatic dissemination, Rectal obstruction, Urothelial carcinoma

Cerebral infarction in patients with cancer is often called Trousseau's syndrome, which is a cancer-associated hypercoagulative state that causes thrombosis; however, the syndrome is rarely caused by bladder cancer. We report a case of Trousseau's syndrome manifesting as multiple cerebral infarctions caused by advanced bladder cancer in a 46-year-old male patient. The patient died due to the infarctions in the hospital. The prognosis of patients with Trousseau's syndrome caused by advanced cancer is poor. According to changing urological clinical settings, considering the risk of Trousseau's syndrome has become crucial for urologists treating patients with advanced cancer. Keywords: Bladder cancer, Cerebral infarction, Trousseau's syndrome, Urothelial cancer

Mechanically robust turbine design with respect to blade vibration is challenging when dealing with nozzle-ring fouling and wear. Especially for engines operating with heavy fuel oil (HFO), the nozzle rings of the turbocharger turbines are prone to severe degradation in terms of contamination with unburned fuel deposits. This contamination will lead to an increased excitation of blade resonances in comparison to the nominal design. Due to the statistical character of contamination, long-term monitoring of blade vibration amplitudes would be beneficial. In the harsh environment of HFO operation, however, conventional blade vibration measurement techniques, such as those using strain gauges or blade tip timing, cannot work reliably for a long period. Thus, the objective of this research is to develop a method that enables the monitoring of turbine blades using pulsation or vibration sensors installed on the stator side. Almost a dozen turbines, both radial and axial, have been examined in order to determine a proper measurement chain/position and analytical method. Even though the challenges specific to the turbocharger turbine application—that high-frequency (up to 50 kHz) acoustic radiation from turbine blades has to be detected by a sensor on the stator side—were demanding, in the course of the investigations several clear examples of turbine blades engine-order resonance detection were gathered. Finally, the proposed method has been tested successfully in a power plant for over one year.

This paper proposes a nonlinear adaptive control method integrated with finite element approximation to obtain the model of the magnetic levitation system of 6 degrees of freedom. Since a magnetically levitated stage is free from friction, it is useful not only to position precisely, but also to measure small force applying to the stage. However, inherent nonlinear characteristics of electromagnetic force make it difficult to measure force correctly. Therefore in this study, with the aim to overcome this difficulty, a control method is proposed to obtain the model of the magnetic levitation system by adopting the manner of model reference adaptive control integrated with finite element approximation for the nonlinear characteristics of electromagnetic force. The controller can compensate the nonlinear characteristics by adjusting PD feedback gains using the obtained model. The parameters of inertia and the center of gravity are also identified to be reflected on a linear reference model. By compensating the nonlinear characteristics of electromagnetic force, the magnetic levitation system behaves as a linear system, which facilitates the position control and the force measurement. The efficiency of this method is shown in an experiment of improving the tracking trajectory control performance.

Endoscopic submucosal dissection (ESD) is recognized as an important technique in the nonsurgical management of early gastrointestinal carcinoma and it is continuously undergoing evolution in terms of technique and equipment. The pocket-creation method was recently developed for overcoming various difficulties such as large tumor size and severe fibrosis in ESD. Circumferential ESDs are rare and pose technical difficulties. We present a case of a circumferential rectal ESD using a pocket-creation method with two pockets. The associated planning, strategies, and outcome of the procedure are discussed.

Antithyroid drugs are generally selected as the first-line treatment for Graves' Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves' disease than in control subjects (P

The (pro)renin receptor [(P)RR] is cleaved by furin to generate soluble (P)RR [s(P)RR], which reflects the status of the tissue renin-angiotensin system. Hemodialysis patients have advanced atherosclerosis. The aim of this study was to investigate the relationships between serum s(P)RR levels and background factors, including indices of atherosclerosis, in hemodialysis patients. Serum s(P)RR levels were measured in hemodialysis patients and clearance of s(P)RR through the membrane of the dialyzer was examined. Furthermore, relationships between serum s(P)RR levels and background factors were assessed. Serum s(P)RR levels were significantly higher in hemodialysis patients (30.4 ± 6.1 ng/ml, n = 258) than those in subjects with normal renal function (21.4 ± 6.2 ng/ml, n = 39, P < 0.0001). Clearance of s(P)RR and creatinine were 56.9 ± 33.5 and 147.6 ± 9.50 ml/min, respectively. Serum s(P)RR levels were significantly higher in those with ankle-brachial index (ABI) of < 0.9, an indicator of severe atherosclerosis, than those with ABI of ≥ 0.9 (32.2 ± 5.9 and 30.1 ± 6.2 ng/ml, respectively, P < 0.05). An association between low ABI and high serum s(P)RR levels was observed even after correction for age, history of smoking, HbA1c, and LDL-C. Serum s(P)RR levels were significantly higher in hemodialysis patients when compared with subjects with normal renal function, although s(P)RR is dialyzed to some extent, but to a lesser extent than creatinine. High serum s(P)RR levels may be associated with atherosclerosis independent of other risk factors, suggesting that serum s(P)RR could be used as a marker for atherosclerotic conditions in hemodialysis patients.

A 50-year-old female became aware of skin yellowing and consulted another hospital where she was diagnosed intraoperatively with duodenal cancer because of lymph node metastases around the aorta. Endoscopy revealed type IIa + IIc cancer distal to the duodenal papilla, and biopsy allowed a diagnosis of well-differentiated adenocarcinoma. Computed tomography revealed a large number of lymph node metastases around the aorta and in the left supraclavicular cavity. The patient was given many regimens of chemotherapy, mainly containing S-1, and multidisciplinary treatment, and achieved long-term survival for 6 years and 1 month. This is a valuable case suggesting the usefulness of this therapeutic approach. In view of the fact that duodenal cancer is a relatively rare disease and the possibility that the incidence of this disease may increase in the future, it seems essential to collect additional data from multicenter prospective studies towards the goal of establishing a standard method of treatment for this disease.

This paper provides an adaptive control method for a magnetic levitation using finite element approximation. Thanks to noncontact and frictionless, magnetic levitation can move smoothly and position precisely an object. In addition, it also makes possible to measure small force applied to the object. However, the fundamental nature of electromagnetic force causes obstructive problems to measuring force correctly. In order to achieve both positioning and measuring force, the finite element approximation works smartly to obtain the model of the magnetic levitation system by the model reference adaptive control technique and correct the deviation of the system from the reference model. As the result, the magnetic levitation system behaves as a reference linear motion system, so that both positioning and measuring force become possible. To show the efficiency of this method, the control system is implemented in the digital signal processors and improve the tracking control performance by obtaining the finite element model of electromagnetic force, parameters of inertia and the center of gravity.

BACKGROUND: For the pending National Claims Database in Japan, researchers will not have access to death information in the enrollment files. We developed and evaluated a claims-based definition of death. METHODOLOGY/PRINCIPAL FINDINGS: We used healthcare claims and enrollment data between January 2005 and August 2009 for 195,193 beneficiaries aged 20 to 74 in 3 private health insurance unions. We developed claims-based definitions of death using discharge or disease status and Charlson comorbidity index (CCI). We calculated sensitivity, specificity and positive predictive values (PPVs) using the enrollment data as a gold standard in the overall population and subgroups divided by demographic and other factors. We also assessed bias and precision in two example studies where an outcome was death. The definition based on the combination of discharge/disease status and CCI provided moderate sensitivity (around 60%) and high specificity (99.99%) and high PPVs (94.8%). In most subgroups, sensitivity of the preferred definition was also around 60% but varied from 28 to 91%. In an example study comparing death rates between two anticancer drug classes, the claims-based definition provided valid and precise hazard ratios (HRs). In another example study comparing two classes of anti-depressants, the HR with the claims-based definition was biased and had lower precision than that with the gold standard definition. CONCLUSIONS/SIGNIFICANCE: The claims-based definitions of death developed in this study had high specificity and PPVs while sensitivity was around 60%. The definitions will be useful in future studies when used with attention to the possible fluctuation of sensitivity in some subpopulations.

Danforth's short tail (Sd) is a semidominant mutation on mouse chromosome 2, characterized by spinal defects, urogenital defects, and anorectal malformations. However, the gene responsible for the Sd phenotype was unknown. In this study, we identified the molecular basis of the Sd mutation. By positional cloning, we identified the insertion of an early transposon in the Sd candidate locus approximately 12-kb upstream of Ptf1a. We found that insertion of the transposon caused overexpression of three neighboring genes, Gm13344, Gm13336, and Ptf1a, in Sd mutant embryos and that the Sd phenotype was not caused by disruption of an as-yet-unknown gene in the candidate locus. Using multiple knockout and knock-in mouse models, we demonstrated that misexpression of Ptf1a, but not of Gm13344 or Gm13336, in the notochord, hindgut, cloaca, and mesonephros was sufficient to replicate the Sd phenotype. The ectopic expression of Ptf1a in the caudal embryo resulted in attenuated expression of Cdx2 and its downstream target genes T, Wnt3a, and Cyp26a1; we conclude that this is the molecular basis of the Sd phenotype. Analysis of Sd mutant mice will provide insight into the development of the spinal column, anus, and kidney.

OBJECTIVE: The (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth. METHODS: Participants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10(th) percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births. RESULTS: Among 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: 73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08-0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020). CONCLUSION: High s(P)RR concentration is associated with a lower SGA birth likelihood.

Aim. Chronic gastritis was assessed serologically, endoscopically and histologically to identify correlations between these methods. Methods. Subjects comprised 319 patients who had provided informed consent. Serological assessment of chronic gastritis was based on the pepsinogen test method. Endoscopic gastritis and histological gastritis were assessed and scored according to the Kimura-Takemoto classification system and the updated Sydney classification system respectively, and correlations between these three methods were studied. Results. Pepsinogen I/II ratio showed a significant correlation to the extent of mononuclear cell infiltration of the gastric corpus. When histological gastritis was divided, on the basis of the distribution of mononuclear cell infiltration, into gastritis limited to the antrum and corpus gastritis, these types were distinguished with high accuracy using a pepsinogen I/II ratio of 3 as the cutoff. A good correlation was also seen between pepsinogen I/II ratio and development of atrophy in endoscopic gastritis, where groups with and without advanced atrophy were also distinguished with high accuracy using a cutoff value of 3. Conclusion. Significant correlations exist between serum pepsinogen levels, endoscopic gastritis, and histological gastritis. Pepsinogen I/II ratio allows prediction of the existence of endoscopic gastritis and histological gastritis, or the extent of their development, with high accuracy.