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Abstract Background Venous air trap chamber designs vary considerably to suit specific continuous renal replacement therapy circuits, with key variables including inflow design and filter presence. Nevertheless, intrachamber flow irregularities do occur and can promote blood coagulation. Therefore, this study employed computational fluid dynamics (CFD) simulations to better understand how venous air trap chamber designs affect flow. Methods The flow within a venous air trap chamber was analyzed through numerical calculations based on CFD, utilizing large eddy simulation. The working fluid was a 33% glycerin solution, and the flow rate was set at 150 ml/min. A model of a venous air trap chamber with a volume of 15 ml served as the computational domain. Calculations were performed for four conditions: horizontal inflow with and without a filter, and vertical inflow with and without a filter. Streamline plots and velocity contour plots were generated to visualize the flow. Results In the horizontal inflow chamber, irrespective of filter presence, ultimately the working fluid exhibited a downstream vortex flow along the chamber walls, dissipating as it progressed, and being faster near the walls than in the chamber center. In the presence of a filter, the working fluid flowed uniformly toward the outlet, while in the absence of a filter the flow became turbulent before reaching the outlet. These observations indicate a streamlining effect of the filter. In the vertical inflow chamber, irrespective of filter presence, the working fluid flowed vertically from the inlet into the main flow direction. Part of the working fluid bounced back at the chamber bottom, underwent upward and downward movements, and eventually flowed out through the outlet. Stagnation was observed at the top of the chamber. Without a filter, more working fluid bounced back from the bottom of the chamber. Conclusions CFD analysis estimated that the flow in a venous air trap chamber is affected by inflow method and filter presence. The “horizontal inflow chamber with filter” was identified as the design creating a smooth and uninterrupted flow throughout the chamber.

Abstract Background Prostate ductal adenocarcinoma, a rare histology observed in 0.4–0.8% of all prostate cancers, is treated similarly to acinar adenocarcinoma but tends to have a higher likelihood of metastasis, recurrence, and poorer prognosis. Case presentation A 73-year-old Asian-Japanese male presented with gross hematuria, with investigations revealing a prostate ductal adenocarcinoma. Subsequent radical prostatectomy indicated a Gleason score of 8 with no lymph node metastasis. Despite initial prostate-specific antigen level reductions post-prostatectomy and salvage radiation therapy due to recurring elevated prostate-specific antigen levels, no recurrence was evident until 13 years later. A tumor in the anterior urethra was identified as metastasis of his prostate ductal adenocarcinoma. Conclusion This report presents an uncommon case of prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-radical prostatectomy.

This study investigated the interoperability of a tomato fruit detection model trained using nighttime images from two greenhouses. The goal was to evaluate the performance of the models in different environmets, including different facilities, cultivation methods, and imaging times. An innovative imaging approach is introduced to eliminate the background, highlight the target plants, and test the adaptability of the model under diverse conditions. The results demonstrate that the tomato fruit detection accuracy improves when the domain of the training dataset contains the test environment. The quantitative results showed high interoperability, achieving an average accuracy (AP50) of 0.973 in the same greenhouse and a stable performance of 0.962 in another greenhouse. The imaging approach controlled the lighting conditions, effectively eliminating the domain-shift problem. However, training on a dataset with low diversity or inferring plant appearance images but not on the training dataset decreased the average accuracy to approximately 0.80, revealing the need for new approaches to overcome fruit occlusion. Importantly, these findings have practical implications for the application of automated tomato fruit set monitoring systems in greenhouses to enhance agricultural efficiency and productivity.

Abstract Background Time-varying exposures like pet ownership pose challenges for identifying critical windows due to multicollinearity when modeled simultaneously. The Distributed Lag Model (DLM) estimates critical windows for time-varying exposures, which are mainly continuous variables. However, applying complex functions such as high-order splines and nonlinear functions within DLMs may not be suitable for situations with limited time points or binary exposure, such as in questionnaire surveys. Objectives (1) We examined the estimation performance of a simple DLM with fractional polynomial function for time-varying binary exposures through simulation experiments. (2) We evaluated the impact of pet ownership on childhood wheezing onset and estimate critical windows. Methods (1) We compared logistic regression including time-varying exposure in separate models, in one model simultaneously, and using DLM. For evaluation, we employed bias, empirical standard error (EmpSE), and mean squared error (MSE). (2) The Japan Environment and Children's Study (JECS) is a prospective birth cohort study of approximately 100,000 parent-child pairs, registered across Japan from 2011 to 2014. We applied DLM to the JECS data up to age 3. The estimated odds ratios (OR) were considered to be within critical windows when they were significant at the 5% level. Results (1) DLM and the separate model exhibited lower bias compared to the simultaneously model. Additionally, both DLM and the simultaneously model demonstrated lower EmpSEs than the separate model. In all scenarios, DLM had lower MSEs than the other methods. Specifically, where critical windows is clearly present and exposure correlation is high, DLM showed MSEs about 1/2 to 1/200 of those of other models. (2) Application of DLM to the JECS data showed that, unlike other models, a significant exposure effect was observed only between the ages of 0 and 6 months. During that periods, the highest ORs were 1.07 (95% confidence interval, 1.01 to 1.14) , observed between the ages of 2 and 5 months. Conclusions (1) A simple DLM improves the accuracy of exposure effect and critical windows estimation. (2) 0–6 months may be the critical windows for the effect of pet ownership on the wheezing onset at 3 years.

A 4-year-old girl presented with complaints of transient speech disorder and left-sided weakness. Magnetic resonance imaging revealed multiple strokes, computed tomography showed a right axillary artery aneurysm of 40 mm, and an angiogram indicated retrograde embolism. She underwent aneurysm resection and reconstruction with a saphenous vein graft. Two years after surgery, a mass lesion occurred in the native artery on the proximal side of the prior surgical anastomosis. Surgical resection and reconstruction were performed. An isolated 1-mm diameter lesion was found in the retrospectively reviewed completion angiogram from the initial surgery, which was the origin of the subsequent progressive lesion. The pathological examination, including after the initial surgery, revealed a myopericytoma.

For olfactory sensors, clear differentiation of complex odour samples requires diverse information. To obtain such information, hardware modifications, such as introducing additional channels with different physical/chemical properties, are usually needed. In this study, we present a new approach to augment the sensing signals of an olfactory sensor by modulating the flow rate of the carrier gas. The headspace vapour of complex odours is measured using a sensing system of nanomechanical sensor (Membrane-type Surface stress Sensor, MSS). The resulting data set is quantitatively evaluated using the Davies-Boulding index (DBI) of principal component analysis (PCA). The increasing number of sensing signals obtained at different gas flow rates leads to a decrease in the DBI, achieving better cluster separation between different odours. Such gas flow effects can be attributed to several factors, including the sample evaporation and the equilibrium of the gas-liquid and gas-solid interfaces. Proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) experiments reveal that the compositions of odour samples vary with the different gas flow rates. It is demonstrated that a simple technique of modulating gas flow rates can significantly improve the differentiation performance of complex odours, providing additional degree of freedom in olfactory sensing.

Objectives: There is a lack of indicators to distinguish between interleukin-6 inhibitors responders and tumor necrosis factor inhibitors responders in the treatment of rheumatoid arthritis. Osteoporosis is a complication of rheumatoid arthritis and is closely related to inflammatory pathology. The purpose of this study was to evaluate whether bone mineral density can distinguish interleukin-6 inhibitors responders from tumor necrosis factor inhibitors responders in rheumatoid arthritis. Methods: Either interleukin-6 inhibitors or tumor necrosis factor inhibitors was introduced as the first biologics to patients naïve to both corticosteroid and osteoporosis treatment. Correlations between baseline bone mineral density and Clinical Disease Activity Index after 3 months were analyzed. Results: The subjects were 26 rheumatoid arthritis patients with a median age of 60 years old, disease duration of 1.4 years, Clinical Disease Activity Index of 13.7, and C-reactive protein of 1.69 mg/dL. The subjects were divided into two groups (high (H) and low (L)) according to their femoral bone mineral density with a cutoff of young adult mean of 80%. Six in group H and 11 in group L received interleukin-6 inhibitors, and nine in group H received tumor necrosis factor inhibitors. Clinical Disease Activity Index remission rate by interleukin-6 inhibitors was significantly greater in group L (8/11 (72.7%)) than in group H (1/6 (16.7%); p

Abstract Background During continuous kidney replacement therapy (CKRT) in patients with sepsis and critical conditions, circuit coagulation can occur, often for unclear reasons. In this study, we investigate how the structure of the venous air trap chamber may contribute to venous air trap chamber coagulation. Clinical data were evaluated and experiments were performed. Methods The clinical evaluation involved patients who underwent continuous hemofiltration (CHF) using an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) hemofilter (AN69ST-CHF) and either an ACH-Σ or Prismaflex CKRT machine in our ICU from April to July 2019. The patient data were divided into two groups based on CKRT machine and the percentage of CHF procedures that could continuously be performed for 22 h (CHF target achievement rate), and coagulation sites were evaluated. Statistical analysis was performed by the Mann–Whitney U test and Pearson’s chi-square test. For in vitro experiments, a system was constructed to circulate a 33% glycerol solution at a flow rate of 150 ml/min. In a venous air trap chamber, fluid dye disappearance times and fluid movements were visually evaluated. Results The clinical evaluation included 22 procedures (8 patients) in the ACH-Σ group and 22 procedures (11 patients) in the Prismaflex group, without significant differences in patient backgrounds between the groups. The CHF target achievement rate was 72.7% (16/22) in the ACH-Σ group and 77.3% (17/22) in the Prismaflex group, revealing no significant difference (p = 0.73). However, significantly fewer venous air trap chamber coagulations were observed in the Prismaflex group (1/5) than in the ACH-Σ group (5/6) (p

For patients with a juxtarenal abdominal aortic aneurysm (JAAA), the chimney technique is an alternative treatment option to open surgical repair. Although the chimney technique is feasible in most cases of JAAA, some anatomical situations may challenge the implantation of a chimney graft through the traditional upper extremity access. Herein, we present a trans-femoral chimney technique using a steerable sheath for chimney endovascular aneurysm repair (chEVAR) of JAAA. This technique allows chEVAR to be completed safely without upper extremity access even in patients at high risk of cerebral embolism including those with a shaggy aorta.

Background Saccular abdominal aortic aneurysms (AAAs) are considered to be at higher risk of rupture than fusiform AAAs, but not much is known about the extent of this risk. Therefore, this study aimed to compare the rupture presentation between fusiform and saccular AAAs. Methods and Results This is a retrospective cohort study on 27 290 patients who underwent primary endovascular repair for a degenerative AAA between 2016 and 2019, and who were registered in the National Clinical Database in Japan. At operation for nonruptured case, the aneurysm diameter was significantly smaller in saccular AAAs than in fusiform AAAs (median, 44.0 versus 51.0 mm; P

Abstract Acute myeloid leukemia (AML) is a malignancy characterized by differentiation arrest of hematopoietic precursor cells. Differentiation therapy is effective for patients with acute promyelocytic leukemia; however, only a few effective differentiation therapies have been established for patients with other AML subtypes. In this study, seven benzimidazole anthelmintics were examined to determine the effects of differentiation on AML cells. The expression of monocyte markers (CD11b and CD14) was elevated after treatment with most benzimidazole anthelmintics. Among these drugs, parbendazole (PBZ) induced AML cell differentiation at low concentration. PBZ induced the monocyte marker expression, KLF4/DPYSL2A gene expression, and apoptosis for 21 AML cell lines with various subtypes and a primary AML sample. Finally, an in vivo analysis using an AML patient-derived xenograft mouse model showed a significant decrease in the chimerism level and prolonged survival in PBZ-treated mice. These findings could lead to a more effective differentiation therapy for AML.

Abstract Background and Aims Emergency medical services for out‐of‐hospital cardiac arrest (OHCA) vary according to region and country, and patient prognosis differs accordingly. In Japan, physicians may provide prehospital care. However, the effect of physician‐present prehospital care on achieving return of spontaneous circulation (ROSC) in patients with cardiac arrest is not clear. Here, we aimed to examine the effect of physician‐present prehospital care on the prognosis of patients with OHCA at our hospital compared with physician‐absent care. Methods In this retrospective, observational study, patients aged ≥18 years with non‐traumatic OHCA from a single center in Saga City, Japan, between April 2011 and December 2019, were included. Patients were divided into two groups, based on prehospital physician presence or absence. Logistic regression analysis was used to determine the association between physician‐present prehospital care and ROSC. Results Of 820 patients with OHCA, 151 had a physician present and 669 did not. Logistic regression analysis with no adjustment showed that the odds ratio (OR) of physician‐present prehospital care for an increased ROSC rate was 1.74 (95% confidence interval [CI]: 1.22−2.48, p = 0.002). Logistic‐regression analysis adjusted for ROSC‐related factors indicated an OR of 1.05 (95% CI: 0.47−2.34, p = 0.914) for physician‐present prehospital care to ROSC. Conclusion Physician‐present prehospital care may not necessarily lead to increased ROSC rates. However, insufficient data limited our study findings. Further studies involving larger sample sizes are warranted.

We describe a case of a focal leg ulcer refractory to conservative therapy. Angiography showed good straight-line flow of the posterior tibial artery and the peroneal artery but pre-occlusive high-grade stenosis of the middle and distal parts of the anterior tibial artery (ATA). Because the stenosis of the ATA was considered a culprit lesion for this focal ulcer, we performed a balloon angioplasty of the ATA, and satisfactory wound healing was achieved 4 months after procedure. In this case, ultra focal ischemia may develop in the anterior compartment of the leg due to impaired flow of the ATA, even in the absence of lesions in the infrapopliteal arteries other than the ATA including a patent pedal arch.

Objective The hallmarks of the chronic inflammatory disease polymyalgia rheumatica (PMR) include pain, and morning stiffness in areas of the neck, shoulder and pelvic girdle. The human leucocyte antigen (HLA) gene was reported to be an important risk factor for PMR, but it has not been analysed precisely, especially in populations other than Europeans.Methods Genotyping of DRB1 and DQB1 was performed in Japanese PMR patients (n=270) and controls (n=413). Associations between allele carrier and genotype frequencies were determined for PMR.Results DRB1*04:05 was associated with a predisposition to PMR (p=0.0006, Pc=0.0193, OR 1.85, 95% CI 1.31 to 2.62). DRB1*09:01 was associated with protection against PMR (p=1.46×10−5, Pc=0.0004, OR 0.40, 95% CI 0.26 to 0.61). A shared epitope (SE) associated with PMR (p=3.07×10−6, OR 2.11, 95% CI 1.54 to 2.88). DQB1*03:03 (p=0.0010, Pc=0.0140, OR 0.52, 95% CI 0.35 to 0.77) was associated with protection against PMR and DQB1*04:01 (p=0.0009, Pc=0.0140, OR 1.82, 95% CI 1.28 to 2.58) was associated with predisposition to PMR. A gene dosage effect was observed for DRB1*09:01 and DQB1*03:03, but not for DRB1*04:05, SE or DQB1*04:01. Haplotype and logistic regression analyses suggested a protective effect for DRB1*09:01.Conclusion This study is the first to demonstrate predisposing associations of DRB1*04:05, SE, and DQB1*04:01, and protective associations of DRB1*09:01 and DQB1*03:03 with PMR in Japanese patients. Our data indicate HLA has predisposing and protective effects on the pathogenesis of PMR.

We have already reported some electroplated magnetic films using aqueous solutions. In the present study, we proposed a fabrication process for electroplated soft magnetic films (Ni films) using gel electrolytes. We added gelatin to the plating baths and confirmed that adding 22 g/L of gelatin enabled us to obtain gel electrolytes. Using the gel electrolytes, we electroplated Ni films and evaluated their structural and magnetic properties. From the evaluation of magnetic properties, we confirmed spontaneous magnetization of the Ni films prepared from the gel electrolyte. For obtaining thick Ni films (>1 μm), we investigated stirring the gel electrolyte during plating. As a result, we found that stirring increased the thickness, and our result suggests that stirring the gel electrolyte is useful to increase the deposition rate. In our experimental conditions, the deposition rate of the plating process was ∼0.25 μm/min. From XRD analysis, the structure of Ni films for gel electrolytes was oriented in the fcc (220) plane and slightly different from that for liquid electrolytes. From these results, we found that soft magnetic films could be obtained from the gel electrolyte and that gel plating is one of the attractive fabrication processes of the thick films.

A 49-year-old man who was a current smoker with a history of hypertension, dyslipidemia, and coronary artery disease after coronary stent placement presented because of abdominal and back pain. Contrast-enhanced computed tomography showed a 30-mm, large hepatic artery aneurysm. Resection of the aneurysm and autogenous vein bypass grafting was performed, which resulted in a successful outcome without any complications. Pathologic examination of the aneurysm confirmed that it was related to immunoglobulin G4 (IgG4). The patient's serum IgG4 level was within the normal range, and no other signs of IgG4-related organ lesions were observed.

Introduction Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%–95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS.Methods and analysis ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%–95% of the target SpO2) or the control (98%–100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1–2 at 90 days after ROSC, to be compared using an intention-to-treat analysis.Ethics and dissemination This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations.Trial registration number UMIN Clinical Trials Registry (UMIN000046914).

Although retrograde in situ branched stent grafting (RIBS) is one possible treatment option for thoracic aortic aneurysms, concerns exist regarding the durability of the stent graft (SG) at the junction between the main SG and the branched SG. We report on the autopsy results of a patient treated with RIBS for a complex aortic arch aneurysm. The patient had died of a nonaortic cause 14 months after the RIBS procedure. On computed tomography analysis and a leak test, the harvested SG was intact without any stent fracture, stenosis, or junctional leak at 1 atm water pressure (760 mm Hg).

Abstract Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease characterized by the production of anti-U1 ribonucleoprotein antibodies and systemic symptoms similar to those of some other autoimmune diseases. HLA-DRB1 polymorphisms are important genetic risk factors for MCTD, but precise associations of DRB1 genotypes with MCTD have not been reported in Japanese people. Genotyping of HLA-DRB1 and -DQB1 was performed in Japanese MCTD patients (n = 116) and controls (n = 413). Associations of specific allele carriers and genotype frequencies with MCTD were analyzed.The following alleles were found to be associated with predisposition to MCTD: HLA-DRB1*04:01 (P = 8.66 × 10–6, Pc = 0.0003, odds ratio [OR] 7.96, 95% confidence interval [CI] 3.13‒20.24) and DRB1*09:01 (P = 0.0189, Pc = 0.5468, OR 1.73, 95% CI 1.12‒2.67). In contrast, the carrier frequency of the DRB1*13:02 allele (P = 0.0032, Pc = 0.0929, OR 0.28, 95% CI 0.11‒0.72) was lower in MCTD patients than in controls. The frequencies of heterozygosity for HLA-DRB1*04:01/*15 (P = 1.88 × 10–7, OR 81.54, 95% CI 4.74‒1402.63) and DRB1*09:01/*15 (P = 0.0061, OR 2.94, 95% CI 1.38‒6.25) were also higher in MCTD patients. Haplotype and logistic regression analyses suggested a predisposing role for HLA-DRB1*04:01, DQB1*03:03, and a protective role for DRB1*13:02. Increased frequencies of HLA-DRB1*04:01/*15 and DRB1*09:01/*15 heterozygous genotypes were found in Japanese MCTD patients.

Subclavian artery aneurysms are rare peripheral artery aneurysms, and open surgical repair is the reference standard treatment. We have reported the case a patient with a right subclavian artery aneurysm who was not indicated for open surgical repair because of comorbidities. Thus, endovascular treatment using the Gore Excluder Iliac Branch Endoprosthesis (WL Gore and Associates, Flagstaff, Ariz) was performed, leading to complete aneurysmal exclusion without perioperative complications. Although anatomic limitations exist, this technique could be alternative treatment option for right subclavian artery aneurysms.

At present, no consensus has been reached regarding the optimal management of stent graft thrombosis in the femoropopliteal artery. We present a case of long thrombosis of a Viabahn stent graft implanted in the superficial femoral artery that was successfully treated by thrombectomy using a trans-Viabahn approach at the mid-thigh segment. The advantages of this approach include that it preserves the common femoral artery and popliteal artery untouched without scarring, allowing for a future site of surgical anastomosis. This technique could be a reasonable approach when performing surgical thrombectomy for stent graft thrombosis in the femoropopliteal artery.

Abstract Objective Rheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD. Methods Sera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay. Results The comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P = 1.13 × 10− 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × 10− 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P = 1.04X10− 11). Conclusion RF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.

Out-of-hospital cardiac arrest (OHCA) is linked to a poor prognosis and remains a public health concern. Several studies have predicted good neurological outcomes of OHCA. In this study, we used the Bayesian network to identify variables closely associated with good neurological survival outcomes in patients with OHCA. This was a retrospective observational study using the Japan Association for Acute Medicine OHCA registry. Fifteen explanatory variables were used, and the outcome was one-month survival with Glasgow-Pittsburgh cerebral performance category (CPC) 1-2. The 2014-2018 dataset was used as training data. The variables selected were identified and a sensitivity analysis was performed. The 2019 dataset was used for the validation analysis. Four variables were identified, including the motor response component of the Glasgow Coma Scale (GCS M), initial rhythm, age, and absence of epinephrine. Estimated probabilities were increased in the following order: GCS M score: 2-6; epinephrine: non-administered; initial rhythm: spontaneous rhythm and shockable; and age:

Background Interstitial lung disease (ILD) occasionally occurs in rheumatoid arthritis (RA) and confers a dismal prognosis. We previously reported that a single-nucleotide variant (SNV) of MUC5B was associated with ILD in RA. However, the pathogenesis of ILD in Japanese patients with RA could not be explained solely by this SNV because its frequency is extremely low in the Japanese population. Here, we examined whether a different idiopathic pulmonary fibrosis susceptibility SNV might be associated with ILD in Japanese patients with RA.Methods Genotyping of rs2609255 (G/T) in FAM13A was conducted in 208 patients with RA with ILD and 420 without chronic lung disease using TaqMan assays.Results A significant association with usual interstitial pneumonia (UIP) in RA was detected for rs2609255 under the allele model (p=0.0092, Pc=0.0276, OR 1.53, 95% CI 1.12 to 2.11) and recessive model for the G allele (p=0.0003, Pc=0.0009, OR 2.63, 95% CI 1.59 to 4.32). FAM13A rs2609255 was significantly associated with UIP in male patients with RA (p=0.0043, OR 3.65, 95% CI 1.52 to 8.73) under the recessive model.Conclusions This study is the first to document an association of rs2609255 with ILD in Japanese patients with RA, implicating it in the pathogenesis of UIP, though studies on the function of rs2609255 are warranted.

Abstract Measuring flow of gases is of fundamental importance yet is typically done with complex equipment. There is, therefore, a longstanding need for a simple and inexpensive means of flow measurement. Here, gas flow is measured using an extremely simple device that consists of an Ar plasma‐treated polydimethylsiloxane (PDMS) slab adhered on a glass substrate with a tight seal. This device does not even have a channel, instead, gas can flow between the PDMS and the glass by deforming the PDMS wall, in other words, by making an interstice as a temporary path for the flow. The formation of the temporary path results in a compressive bending stress at the inner wall of the path, which leads to the formation of well‐ordered wrinkles, and hence, the emergence of structural color that changes the optical transmittance of the device. Although it is very simple, this setup works sufficiently well to measure arbitrary gases and analyzes their flow rates, densities, and viscosities based on the change in color. It is also demonstrated that this technique is applicable to the flow‐induced display of a pattern such as a logo for advanced applications.

Abstract A 22‐year‐old, female patient with systemic lupus erythematosus experienced bacterial enteritis. A stool Gram stain revealed Campylobacter. Non‐typhoidal Salmonella was detected in a stool culture, and Campylobacter jejuni was detected in a blood culture. Based on these findings, co‐infection of Campylobacter jejuni and non‐typhoidal Salmonella was diagnosed.

Titania and silica have been recognized as potential drug delivery system (DDS) carriers. For this application, controllable biocompatibility and the suppression of the initial burst are required, which can be provided by a calcium phosphate (CP) coating. However, it is difficult to control the morphology of a CP coating on the surface of carrier particles owing to the homogeneous nucleation of CP. In this study, we report the development of a CP-coating method that homogeneously corresponds to the shapes of silica–titania (SiTi) porous nanoparticles. We also demonstrate that controlled surface roughness of CP coatings could be achieved in SBF using SiTi nanoparticles with a well-defined spherical shape, a uniform size, and a tunable nanoporous structure. The precipitation of CP was performed on mono-dispersed porous SiTi nanoparticles with different Si/Ti molar ratios and pore sizes. The pore size distribution was found to significantly affect the CP coating in SBF immersion; the surfaces of the nanoparticles with bimodal pore sizes of 0.7 and 1.1–1.2 nm became rough after CP precipitation, while those with a unimodal pore size of 0.7 nm remained smooth, indicating that these two pore sizes serve as different nucleation sites that lead to different surface morphologies.

Abstract It is known that there are no primary odors that can represent any other odors with their combination. Here, we propose an alternative approach: “quasi” primary odors. This approach comprises the following condition and method: (1) within a collected dataset and (2) by the machine learning-based endpoint detection. The quasi-primary odors are selected from the odors included in a collected odor dataset according to the endpoint score. While it is limited within the given dataset, the combination of such quasi-primary odors with certain ratios can reproduce any other odor in the dataset. To visually demonstrate this approach, the three quasi-primary odors having top three high endpoint scores are assigned to the vertices of a chromaticity triangle with red, green, and blue. Then, the other odors in the dataset are projected onto the chromaticity triangle to have their unique colors. The number of quasi-primary odors is not limited to three but can be set to an arbitrary number. With this approach, one can first find “extreme” odors (i.e., quasi-primary odors) in a given odor dataset, and then, reproduce any other odor in the dataset or even synthesize a new arbitrary odor by combining such quasi-primary odors with certain ratios.

Chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway diseases (ADs), are common complications of rheumatoid arthritis (RA). Rheumatoid factor (RF) and anti-citrullinated peptide antibodies are reported to be associated with CLD in RA patients. The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (Abs) is associated with clinically amyopathic dermatomyositis developing into rapidly progressive ILD. However, few studies on anti-MDA5 Abs in RA have been published. Here, we analyzed the association of anti-MDA5 Abs with CLD complications in RA. Anti-MDA5 Abs were quantified in sera from RA patients with or without CLD. Anti-MDA5 Ab levels were higher in RA patients with ADs than without (mean ± SDM, 4.4 ± 2.4 vs. 4.0 ± 4.2, p = 0.0001). AUC values of anti-MDA5 Ab and RF ROC curves were similar in RA patients with or without CLD (0.578, 95%CI 0.530–0.627 and 0.579, 95%CI 0.530–0.627, respectively, p = 0.9411). Multiple logistic regression analysis of anti-MDA5 Abs and clinical characteristics yielded an MDA5-index with a higher AUC value than anti-MDA5 Ab alone (0.694, 95%CI 0.648–0.740, p = 5.08 × 10−5). Anti-MDA5 Abs were associated with ADs in RA patients and could represent a biomarker for CLD, similar to RF. The involvement of anti-MDA5 Abs in the pathogenesis of ADs in RA is proposed.

Background: Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in RPA3-UMAD1 . We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association. Methods: Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease. Results: No association was detected for rs12702634 with ILD in RA ( P = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association ( P = .0996, OR 1.52, 95% CI 0.92–2.49). Conclusions: The present study demonstrated no association of RPA3-UMAD1 rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.

Objectives: The severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019. A serological test is conducted to determine prior infection by severe acute respiratory syndrome coronavirus 2. We investigated whether the results of anti-severe acute respiratory syndrome coronavirus 2 antibody tests are modified in patients with rheumatoid arthritis. Methods: Patients in Japan with rheumatoid arthritis were recruited at Sagamihara Hospital from July 2014 to October 2015 ( n = 38; 2014 cohort) and at Tokyo Hospital from June to October 2020 ( n = 93; 2020 cohort). Anti-severe acute respiratory syndrome coronavirus 2 antibodies were measured by electrochemiluminescence immunoassay or immunochromatographic assay. Results: Anti-severe acute respiratory syndrome coronavirus 2 antibodies were not detected in any of the samples from rheumatoid arthritis patients tested by electrochemiluminescence immunoassay. Anti-severe acute respiratory syndrome coronavirus 2 antibodies were detected by immunochromatographic assay in the 3 (7.9%) serum samples in the 2014 cohort and 15 (16.1%) serum samples in the 2020 cohort. The IgM rheumatoid factor levels were increased in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (mean ± standard deviation (IU/ml), 1223.0 ± 1308.7 versus 503.6 ± 1947.2; P = 0.0101). The levels of IgG rheumatoid factor were also upregulated in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (4.0 ± 0.7 versus 2.4 ± 0.9; P = 0.0013). Conclusion: The results of IgM anti-severe acute respiratory syndrome coronavirus 2 antibody testing by immunochromatographic assay are modified by IgM or IgG rheumatoid factors in rheumatoid arthritis patients.

Objective We aimed to standardize the definition of low disease activity in rheumatoid arthritis (RA) using the Outcome Measures in Rheumatology (OMERACT) group's proposed definition of minimal disease activity. Method Based on a nationwide RA database, we proposed new Boolean low disease activity criteria using OMERACT's core set definition of minimal disease activity that requires the fulfillment of at least five of the following seven core set measures: a pain score of 2 or less, a swollen joint count (SJC28) of 1 or fewer, a tender joint count of 1 or fewer, a Health Assessment Questionnaire score of 0.5 or less, a Physician's Global Assessment score of 1.5 or less, a Patient's Global Assessment score of 2 or less, and an erythrocyte sedimentation rate (ESR) of 20 mm/h or less. Using receiver operating characteristic analysis, we determined the cutoffs for the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Routine Assessment of Patient Index Data 3 (RAPID3), and the Disease Activity Score in 28 joints (DAS28)–ESR. Results Of 8298 patients, 56.2% met the proposed Boolean low disease activity criteria. We determined an SDAI score of 5.5 or less and a CDAI score of 5 or less to be the new cutoffs, and we chose a DAS28 of 2.85 or less (the original cutoff for DAS‐based minimal disease activity) and a RAPID3 score of 6 or less (the original cutoff for RAPID3‐based low disease activity) with or without a swollen joint count (SJC) (SJC of 2 or fewer) as the cutoffs for DAS28 and RAPID3. The agreement between the new cutoffs for DAS28 of 2.85 or less vs. CDAI score of 5 or less, CDAI score of 5 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), and DAS28 of 2.85 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), was 0.619, 0.612 (0.702), and 0.474 (0.531), respectively. Conclusion OMERACT's minimal disease activity definition may be used to standardize the criteria for low disease activity.

To conduct an appropriate medical interview, education and clinical experience are necessary. The usefulness of computer-based medical diagnostic support systems has been reported in medical interviewing. However, only a few reports have actually applied these systems and noted changes in the quality of the medical interview of residents. We aimed to examine how the use of a medical interview support application changes the medical interviews of residents. The study was conducted on 15 residents (with less than two years post-graduation) and ran from November 2020 to March 2021. Faculty members played the role of simulated patients in 20 cases, and the residents conducted the medical interviews. In 10 of the 20 cases, a medical interview support application was used. After the interview, the residents were asked to list up to 10 differential diseases; the interview was considered appropriate if it included the disease portrayed by the simulated patient. Furthermore, the duration of the medical interview, the number of questions asked, and changes in stress parameters were evaluated. The use of a medical interview support application increased the percentage of appropriate medical interviews. Considering the frequency, the use of a medical interview support application increased the rate of appropriate medical interviews in the rare disease group, as well as the number of questions and duration of the interviews. No stress reduction was observed. The medical interview support application may be a useful tool in identifying appropriate differential diseases during medical interviews by residents.

Microelectromechanical systems (MEMS)-based piezoresistive nanomechanical sensors are compact sensing platforms widely employed in vapor sensing, environmental monitoring, and biosensing. Despite their extensive utility, their lower sensitivity relative to their optical readout counterparts has been a limiting factor, constraining the wider application of this technology. Prior research has suggested that alternative silicon orientations, such as 〈111〉 orientations in (110) wafers, can significantly improve the sensitivity of piezoresistive sensors. However, the complexity of optimizing two-dimensional stress distribution and handling anisotropic elasticity has made device design a formidable task, leaving this promising avenue largely unexplored. To address this challenge, we employ density-based topology optimization to generate a series of optimized designs for piezoresistive nanomechanical sensors manufactured along 〈111〉 orientations. The properties of the immobilization layer—the functional coating on the sensor—are parametrically varied to explore optimal designs. Our study reveals a transition in optimized designs from a double-cantilever configuration to a suspended platform configuration, dictated by the stiffness ratio between the immobilization layer and the silicon layer. This transition is attributed to the shift in the neutral plane and the prevailing stress relaxation mechanism. In addition, we scrutinize the effects of piezoresistor geometry and find that the optimized designs depend asymmetrically on the piezoresistor position, a characteristic stemming from the anisotropic elasticity in 〈111〉 orientations. These optimized designs, verified by finite element analysis (FEA), demonstrate a notable improvement in sensitivity of more than 20% when benchmarked against traditional rectangular designs and equivalent optimized designs in conventional orientations, thereby validating the effectiveness of the present model. This study provides crucial knowledge for the design of piezoresistive biosensors, facilitating more efficient geometric design in future sensor development.

Quantifying the viscosity of a gas is of great importance in determining its properties and can even be used to identify what the gas is. While many techniques exist for measuring the viscosities of gases, it is still challenging to probe gases with a simple, robust setup that will be useful for practical applications. We introduce a facile approach to estimating gas viscosity using a strain gauge inserted in a straight microchannel with a height smaller than that of the gauge. Using a constrained geometry for the strain gauge, in which part of the gauge deforms the channel to generate initial gauge strain that can be transduced into pressure, the pressure change induced via fluid flow was measured. The change was found to linearly correlate with fluid viscosity, allowing estimation of the viscosities of gases with a simple device.

Castleman’s disease was first reported in 1954 by Castleman et al. and identified as an uncommon lymphoproliferative disorder. In most cases, Castleman’s diseases are detected in the chest, head, and neck. A 71-year-old man was referred to our hospital due to a retroperitoneal tumor in the para-aortic area by computed tomography (CT). Positron emission tomography-CT revealed an uptake in this tumor, suggesting malignant diseases. Laparoscopic tumorectomy was performed, and the pathological diagnosis was Castleman’s disease, hyaline vascular type. No evidence of recurrence was observed 20 months after surgery. We herein report a rare case of retroperitoneal Castleman’s disease.

IgG4-related disease is diagnosed when both the elevation of the serum IgG4 level and invasion of IgG4-positive interstitial cells and sclerosis to a tumor are noted. Some cases have demonstrated malignant disease. In the head and neck lesion in particular, IgG4-producing mucosa-associated lymphoid tissue (MALT) lymphoma has arisen during the treatment of IgG4-related disease. We herein report the first case of IgG4-producing MALT lymphoma during the treatment of IgG4-related disease in the renal hilum. A 79-year-old man was being followed for autoimmune pancreatitis and IgG4-related sclerosing cholangitis. During follow-up, magnetic resonance cholangiopancreatography detected a mass in the renal hilum, so he was referred to our department for a further examination. Positron emission tomography-computed tomography detected a standard uptake of 9.7, and the tumor size was gradually increasing. Due to these findings, laparoscopic nephro-ureterectomy was performed. A pathological examination revealed IgG4-producing marginal zone B cell lymphoma. We herein report a rare case of IgG4-producing B cell lymphoma in the renal hilum.

Background Delirium has been shown to prolong the length of intensive care unit stay, hospitalization, and duration of ventilatory control, in addition to increasing the use of sedatives and increasing the medical costs. Although there have been a number of reports referring to risk factors for the development of delirium, no model has been developed to predict delirium in trauma patients at the time of admission. This study aimed to create a scoring system that predicts delirium in trauma patients.Methods In this single-center, retrospective, observational study, trauma patients aged 18 years and older requiring hospitalization more than 48 hours were included and divided into the development and validation cohorts. Univariate analysis was performed in the development cohort to identify factors significantly associated with prediction of delirium. The final scoring system for predicting delirium was developed using multivariate analysis and internal validation was performed.Results Of the 308 patients in the development cohort, 91 developed delirium. Clinical Frailty Score, fibrin/fibrinogen degradation products, low body mass index, lactate level, and Glasgow Coma Scale score were independently associated with the development of delirium. We developed a scoring system using these factors and calculated the delirium predictive score, which had an area under the curve of 0.85. In the validation cohort, 46 of 206 patients developed delirium. The area under the curve for the validation cohort was 0.86, and the calibration plot analysis revealed the scoring system was well calibrated in the validation cohort.Discussion This scoring system for predicting delirium in trauma patients consists of only five risk factors. Delirium prediction at the time of admission may be useful in clinical practice.Level of evidence Prognostic and epidemiological, level III.

Late-onset hypogonadism, a male age-related syndrome characterized by a decline in testosterone production in the testes, is commonly treated with testosterone replacement therapy, which has adverse side effects. Therefore, an alternative treatment is highly sought. Supplementation of a high dosage of biotin, a water-soluble vitamin that functions as a coenzyme for carboxylases involved in carbohydrate, lipid, and amino acid metabolism, has been shown to influence testis functions. However, the involvement of biotin in testis steroidogenesis has not been well clarified. In this study, we examined the effect of biotin on testosterone levels in mice and testis-derived cells. In mice, intraperitoneal treatment with biotin (1.5 mg/kg body weight) enhanced testosterone levels in the serum and testes, without elevating serum levels of pituitary luteinizing hormone. To investigate the mechanism in which biotin increased the testosterone level, mice testis-derived I-10 cells were used. The cells treated with biotin increased testosterone production in a dose- and time-dependent manner. Biotin treatment elevated intracellular cyclic adenosine monophosphate levels via adenylate cyclase activation, followed by the activation of protein kinase A and testosterone production. These results suggest that biotin may have the potential to improve age-related male syndromes associated with declining testosterone production.

Nanomechanical sensors have gained significant attention as powerful tools for detecting, distinguishing, and identifying target analytes, especially odors that are composed of a complex mixture of gaseous molecules. Nanomechanical sensors and their arrays are a promising platform for artificial olfaction in combination with data processing technologies, including machine learning techniques. This paper reviews the background of nanomechanical sensors, especially conventional cantilever-type sensors. Then, we focus on one of the optimized structures for static mode operation, a nanomechanical Membrane-type Surface stress Sensor (MSS), and discuss recent advances in MSS and their applications towards artificial olfaction.

Theranostics (bifunction of therapeutics and diagnostics) has attracted increasing attention due to its efficiency that can reduce the physical and financial burden on patients. One of the promising materials for theranostics is calcium phosphate (CP) and it is biocompatible and can be functionalized not only with drug molecules but also with rare earth ions to show photoluminescence that is necessary for the diagnostic purpose. Such the CP-based hybrids are formed in vivo by interacting between functional groups of organic molecules and inorganic ions. It is of great importance to elucidate the interaction of CP with the photofunctional species and the drug molecules to clarify the relationship between the existing state and function. Well-designed photofunctional CPs will contribute to biomedical fields as highly-functional ormultifunctional theranostic materials at the nanoscales. In this review, we describe the hybridization between CPs and heterogeneous species, mainly focusing on europium(III) ion and methylene blue molecule as the representative photofunctional species for theranostics applications.

Interstitial lung disease (ILD) is frequently a complication of rheumatoid arthritis (RA) as an extra-articular manifestation which has a poor prognosis. Acute-onset diffuse ILD (AoDILD) occasionally occurs in RA and includes acute exacerbation of ILD, drug-induced ILD, and Pneumocystis pneumonia. AoDILD also confers a poor prognosis in RA. Previously-established biomarkers for ILD include Krebs von den lungen-6 and surfactant protein-D originally defined in patients with idiopathic pulmonary fibrosis; the sensitivity of these markers for RA-associated ILD (RA-ILD) is low. Although many studies on ILD markers have been performed in idiopathic pulmonary fibrosis, only a few validation studies in RA-ILD or AoDILD have been reported. Biomarkers for RA-ILD and AoDILD are thus still required. Recently, genomic, cytokine, antibody, and metabolomic profiles of RA-ILD or AoDILD have been investigated with the aim of improving biomarkers. In this review, we summarize current preliminary data on these potential biomarkers for RA-ILD or AoDILD. The development of biomarkers on RA-ILD has only just begun. When validated, such candidate biomarkers will provide valuable information on pathogenesis, prognosis, and drug responses in RA-ILD in future.

Abstract Background Previous studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan. Methods We investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance. Results Mean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index. Conclusions RA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.

Objectives: Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers.Methods: Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry.Results: A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate Q = 1.87 × 10−11 and 7.09 × 10−6, respectively), and glycerol was higher (Q = 1.20 × 10−6), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867–0.968, sensitivity 0.880, specificity 0.780).Conclusions: Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.

We describe the case of a 74-year-old man with a thoracic aortic aneurysm with a bovine arch who underwent fenestrated endovascular repair of aortic arch aneurysm using the Najuta stent graft (Kawasumi Laboratories, Inc, Tokyo, Japan). He has had a previous endovascular aneurysm repair and femoropopliteal bypass for abdominal aortic aneurysm combined with peripheral arterial disease. The Najuta stent graft was inserted and deployed at zone 0 with delicate positional adjustment of the fenestration of the stent graft to the brachiocephalic trunk. There was no endoleak or complication. His postoperative course was uneventful. At 7-month follow-up, complete exclusion of the aneurysm was noted. The Najuta stent graft repair of aortic arch aneurysms is a safe and effective treatment option for patients with a bovine arch.

Abstract Background Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. Methods A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. Results The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p