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705 Background: Nanoliposomal irinotecan plus fluorouracil and folinic acid (nal-IRI/FU/LV; NFF) is the standard regimen after gemcitabine-based therapy for unresectable or recurrent pancreatic cancer (urPC). However, the efficacy and safety of NFF in patients who previously received irinotecan-based chemotherapy remain unclear. Methods: This retrospective study collected data from patients with urPC who received at least one previous chemotherapy before receiving NFF therapy at 21 hospitals in Japan between June 2020 and May 2021 (NAPOLEON-2 study). We analyzed antitumor efficacy, progression-free survival (PFS), and overall survival (OS) after the initiation of NFF and compared adverse events (AEs) between previous irinotecan users and non-users. Results: NFF was administered to 161 patients. The median follow-up period was 7.3 months (95% confidence interval [CI] = 5.6–8.9). All patients received prior gemcitabine-based therapy, and NFF was administered as the second-, third-, and fourth-or-later-line chemotherapy in 104, 41, and 16 patients, respectively. Eighteen patients (11%) previously received irinotecan. Patients’ characteristics did not significantly differ between irinotecan users (n = 18) and non-users (n = 143), excluding age (mean [range], 64 [38–78] vs. 68 [47–85] years; p = 0.01), the lung metastasis rate (44% vs. 14%; p < 0.01), the treatment line (2nd/3rd/4th-or-later, 0%/56%/44% vs. 73%/22%/6%; p < 0.01), and the pretreatment period (15.3 [6.8–45.0] vs. 9.1 [1.4–36.2] months; p < 0.01). The median relative dose intensities of nal-IRI were 87.1% and 81.1% in irinotecan users and non-users, respectively (p = 0.28), and those of FU were 93.5% and 89.2%, respectively (p = 0.54). The objective response rate (6% vs. 5%; p = 0.90), disease control rate (44% vs. 53%; p = 0.49), PFS (2.8 months vs. 3.6 months; hazard ratio [HR] = 1.23; 95% CI = 0.74–2.05; p = 0.42), and OS (9.2 months vs. 8.0 months; HR = 0.88; 95% CI = 0.49–1.57; p = 0.66) did not differ between irinotecan users and non-users, nor did the rates of Grade 3/4 hematological (p = 0.68) and non-hematological (p = 0.13) AEs. Among irinotecan users, the duration of irinotecan-based therapy and the irinotecan-free interval before NFF did not affect the efficacy of NFF. Conclusions: NFF might be effective and safe even in patients with urPC who received irinotecan-based chemotherapy irrespective of its duration or the interval to NFF. Therefore, NFF is a possible treatment option after irinotecan-based chemotherapy. Further studies with a sufficient number of patients and a prospective design are warranted to examine the efficacy of NFF after irinotecan-based chemotherapy.

Childhood cancer survivors (CCSs) from high-grade malignancies, such as high-risk neuroblastoma, have been increased, and second malignant neoplasm, becomes a serious problem for CCSs. However, detailed reports about rare types of second cancer such as gastric cancer remain limited. We herein reported a female patient who developed diffuse type gastric carcinoma after 21 years from completion of treatment to high-risk neuroblastoma. We reviewed the previous cohort studies for second gastrointestinal cancer in CCSs and the case reports with second gastric carcinoma for CCSs. We presumed second gastric cancer was refractory for CCSs as well as for adult cancer survivors.

We propose a new technique that evaluates the structures of car interiors by the following two algorithms, based on visual processing in the brain. (1) Medial axes reveal the imaginary skeletal structures within objects. (2) Saliency maps identify the areas attracting attention in visual scenes. Integration of these techniques revealed hidden axes characterizing the global structures of car dashboards, which are possibly more alluring than explicit features. Furthermore, the variety of such hidden axes across different cars/brands can be summarized in reduced dimensional spaces. Because features revealed by this technique are consistent with the framework of universal rules for aesthetic experiences (e.g., symmetry and perceptual problem solving), this could be useful to evaluate some aspects of aesthetic values quantitatively in car interiors.

Background: Achieving clear visibility through a windshield is one of the crucial factors in manufacturing a safe and comfortable vehicle. The optic flow (OF) through the windshield has been reported to divert attention and could impair visibility. Although a growing number of behavioral and neuroimaging studies have assessed drivers' attention in various driving scenarios, there is still little evidence of a relationship between OF, windshield shape, and driver's attentional efficacy. The purpose of this research was to examine this relationship. Methods: First, we quantified the OF across the windshield in a simulated driving scenario with either of two types of the windshield (a tilted or vertical pillar) at different speeds (60 km/h or 160 km/h) and found more upward OF along the tilted pillar than along the vertical pillar. Therefore, we hypothesized that the predominance of upward OF around the windshield along a tilted pillar could distract a driver and that we could observe the corresponding neural activity. Magnetic resonance scans were then obtained while the subjects performed a visual detection task while watching the driving scene used in the OF analysis. The subjects were required to press a button as rapidly as possible when a target appeared at one of five positions (leftmost, left, center, right, and rightmost). Results: We found that the reaction time (RT) on exposure to a tilted pillar was longer than that on exposure to a vertical pillar in the leftmost and rightmost conditions. Furthermore, there was more brain activity in the precuneus when the pillar was tilted than when it was vertical in the rightmost condition near the pillar. In a separate analysis, activation in the precuneus was found to reflect relative changes in the amount of upward OF when the target was at the rightmost position. Conclusions: Overall, these observations suggest that activation in the precuneus may reflect extraneous cognitive load driven by upward OF along the pillar and could distract visual attention. The findings of this study highlight the value of a cognitive neuroscientific approach to research and development in the motor vehicle manufacturing industry.

Humans feel forces or weights while grasping and manipulating an object. There is a difference between the physical and perceived forces because the physical characteristics of an object and/or human psychophysical characteristics affect perceived force. Sense of effort plays an important role in deciding the movement made by humans. In this study, we propose a computational method to predict the perceived force by evaluating the muscle activity as a function of effort in the operation of a steering wheel based on a 3D-musculoskeletal model simulation. We found that the perceived-force characteristics depend on the driving posture, though the applied force is the same. We evaluated the results, and showed that the mean of the absolute error is 1.78 N for the experiments conducted on four different vehicles in commercially available.

This study evaluated the association between early tumor response at 8 weeks, previously reported as a positive outcome prognosticator, and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients enrolled in the ABSOLUTE trial.HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D) utility index score in patients with complete response (CR) + partial response (PR) and progressive disease (PD) at 8 weeks, and time-to-deterioration (TtD) of the EQ-5D score, with the preset minimally important difference (MID) of 0.05, was compared between these populations. Among the enrolled patients, 143 and 160 patients were assessable in weekly solvent-based paclitaxel (Sb-PTX) arm and weekly nanoparticle albumin-bound paclitaxel (nab-PTX) arm, respectively.Changes of the EQ-5D score from baseline to 8 weeks in the nab-PTX arm were 0.0009 and - 0.1229 in CR + PR and PD patients, respectively; the corresponding values for the Sb-PTX arm were - 0.0019 and - 0.1549. For both treatments, changes of the EQ-5D score from baseline at 8 weeks were significantly larger in patients with PD than in those with CR + PR. The median TtD was 3.9 and 2.2 months in patients with CR + PR and PD, respectively, for nab-PTX [hazard ratio (HR) = 0.595, 95% confidence interval (CI) 0.358-0.989]. For Sb-PTX, the corresponding values were 4.7 and 2.0 months (HR = 0.494, 95% CI 0.291-0.841).Early tumor shrinkage was associated with maintained HRQOL in AGC patients on the second-line chemotherapy with taxanes.

Background: A high level of house dust mite (HDM) allergens in a living environment is a risk factor for both sensitization to these allergens and asthmatic attacks. We previously showed that plasma cluster ions (PCIs) impaired the IgE-binding capacity of atomized crude allergens prepared from Japanese cedar pollen and fungus under experimental conditions. Objective: We evaluated the capacity of PCIs to impair the IgE-binding capacity of airborne HDM allergens under a simulated indoor environmental condition. Methods: For the determination of the effects of PCIs on HDM allergens under an experimental condition, HDM extract was atomized as aqueous mist into a cylindrical experimental apparatus filled with PCIs. For the evaluation of the effects of PCIs under a simulated natural indoor environmental condition, dried HDM allergens were floated as airborne particles in an acryl cubic apparatus in the presence of PCIs. The IgE-binding capacities of the PCI- and sham-treated HDM allergens were analyzed by an ELISA. Results: The IgE-binding capacity of the HDM allergens was significantly impaired after PCI treatment compared to that after sham treatment under both experimental and simulated environmental conditions. The ELISA results demonstrated that the IgE-binding capacities of HDM allergens after PCI treatment showed 68 and 74% reductions compared to those after sham treatment under the experimental and simulated environmental conditions, respectively. Conclusions: PCIs have the capacity to impair the IgE-binding capacity of airborne HDM allergens in a simulated environmental condition.

Mite antigens play important roles in the pathogenesis of atopic dermatitis (AD). We recently developed a novel air cleaner (KC-850U) using charged plasma cluster ions to eliminate a variety of allergens from house environments. The present work demonstrates the ability of KC-850U to decrease the symptoms of AD induced by mite allergens. Pooled sera from the conventional NC/Nga mice, and AD model animals, were incubated with varying concentrations of the control and KC-850U-pretreated allergens extracted from mite. The incubated mixtures were transferred to wells coated with intact allergens and subjected to ELISA to measure the amounts of immunoglobulin E (IgE) bound to the wells. Kinetic analysis revealed that exposure of mite extracts to plasma cluster ions destructed about 95% of the epitopes of the allergens. The specific pathogen-free and conventional mice were housed in rooms equipped with either KC-850U or a standard air cleaner and observed their dermal symptom for 2 weeks. Dermatological examination revealed the AD symptom of the conventional mice housed in a room equipped with an air cleaner. In contrast, the symptoms which became apparent during the experiments were suppressed remarkably exposing mice to plasma cluster ions. These observations suggested that plasma cluster ions generated by KC-850U destroyed the epitopes of mite allergens and suppressed the symptoms of AD in the mice.

プラズマクラスターイオン®の肌保湿効果および快適性向上作用について検討するため，肌の乾燥を感じやすい健常女性 32 名を対象とした単盲検ランダム化 2 試験区クロスオーバー試験を実施した．対照と比較して，プラズマクラスターイオン濃度 2.5 万個/cm3 では，有意な肌水分量の増加がみられ，イオン濃度 7 千個/cm3 では，有意な快適感の上昇がみられた．プラズマクラスターイオンが肌保湿効果や快適感向上作用を有することが示唆された．

In order to clarify the mechanism of the host response to influenza virus, gene-expression profiles of peripheral blood obtained from paediatric patients with influenza were investigated by oligonucleotide microarray. In the acute phase of influenza, 200 genes were upregulated and 20 genes were downregulated compared with their expression in the convalescent phase. Interferon-regulated genes, such as interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) and vipirin, were strongly upregulated in the acute phase. Gene ontology analysis showed that immune response genes were highly overrepresented among the upregulated genes. Gene-expression profiles of influenza patients with and without febrile convulsion were also studied. In patients with febrile convulsion, 22 genes were upregulated and five were downregulated compared with their expression in patients without febrile convulsion. These results should help to clarify the pathogenesis of influenza and its neurological complications.

Epstein-Barr virus (EBV) is known to be a causative agent of hemophagocytic lymphohistiocytosis (HLH). To investigate association of apoptosis in the pathogenesis of EBV-associated HLH, the serum EBV loads, and serum concentrations of soluble tumor necrosis factor receptor 1 (sTNF-R1), soluble Fas ligand, and cytochrome c were examined in 15 patients with EBV-associated HLH and 24 patients with infectious mononucleosis (IM). Levels of sTNF-R1 are known to reflect the biological activity of TNF-alpha and cytochrome c is a specific marker of apoptosis. EBV loads, and concentrations of sTNF-R1 and cytochrome c were significantly higher in patients with EBV-associated HLH than in patients with IM. On the other hand, there were no statistically significant differences in the concentrations of soluble Fas ligand. In patients with EBV-associated HLH, EBV loads, concentrations of sTNF-R1, and cytochrome c were correlated with each other. These results suggest that apoptosis, which is dependent on the EBV load and could be mediated by TNF-alpha, plays a major role in the pathophysiology of EBV-associated HLH.

This paper proposes a scheme for human force manipulability (HFM) based on the use of isometric joint torque properties to simulate the spatial characteristics of human operation forces at an end-point of a limb with feasible magnitudes for a specified limb posture. This is also applied to the evaluation/prediction of operational comfort (OC) when manually operating a human-machine interface. The effectiveness of HFM is investigated through two experiments and computer simulations of humans generating forces by using their upper extremities. Operation force generation with maximum isometric effort can be roughly estimated with an HFM measure computed from information on the arm posture during a maintained posture. The layout of a human-machine interface is then discussed based on the results of operational experiments using an electric gear-shifting system originally developed for robotic devices. The results indicate a strong relationship between the spatial characteristics of the HFM and OC levels when shifting, and the OC is predicted by using a multiple regression model with HFM measures.

Infantile hepatitis is occasionally seen in apparently healthy children. In most cases, the etiology of the infection is uncertain. However, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), human herpesvirus-7 (HHV-7), human parvovirus B19, and TT virus (TTV) are considered to be associated with hepatitis in children. The objective of this study was to investigate the correlations between these viruses and infantile hepatitis. Twenty-six children from 1 to 24 months old (median age, 7 months) who had liver dysfunction of unknown etiology were enrolled in this study. Plasma samples were examined by a real-time PCR assay for CMV, EBV, HHV-6, HHV-7, parvovirus B19, and TTV DNA. The DNA of CMV was detected in the plasma of four patients (15.4%) and was detected significantly more often in the patient group than in the control group. The CMV-infected patients were 1 to 3 months old, which was significantly younger than the remaining patients. The serological findings did not always correlate with the results of the real-time PCR assay. The DNA of TTV was detected in four patients (15.4%), while human parvovirus B19 DNA was detected in three (11.5%). However, the detection frequencies of these viral DNAs were not significantly different from those in the control groups, and some of these patients had co-infections. These results indicate that CMV might be one of the major pathogens responsible for infantile hepatitis; however, serological tests have limited utility for the diagnosis of CMV infection in young children.

Compaction of TiO2 suspended particles utilizing the hydrophilic/hydrophobic transition of a cationic thermosensitive copolymer of N-isopropylacrylamide (NIPAM) and N,N-dimethylaminopropylacrylamide (DMAPAA) was examined. The surface of suspended TiO2 particles were sufficiently covered with the adsorbed polymer molecules at room temperature, and the suspension was subsequently heated above the transition temperature of the polymer. The thrusting motion of a plunger was used in order to provide an adequate mechanical force to compact the TiO2 suspended particles. The transition temperature was dependent on the DMAPAA content in the copolymer and the pH of the suspension. The transition temperature increased with increasing DMAPAA content and decreased with increasing pH. While suspended TiO2 particles were not compacted with poly(NIPAM), hard compacted sludge was readily obtained for cationic copolymer even if the content of DMAPAA groups was as low as 0.23 mol%. Furthermore, residual polymer molecules in the supernatant were not detected even if the polymer dosage was increased. These findings were attributed to the hydrophobic interaction of thermosensitive copolymer molecules adsorbed on TiO2 particles.

Pressure fluctuation occurs in an oil pressure pump in the nature of the machine. It becomes a cause of a vibration and a noise of a building where the oil pressure pump are set because the pressure fluctuation gives a fluctuating force on floors and walls of the building. So it is important to reduce the vibration and noise from an environmental point of view. A side branch is often used to reduce the pressure fluctuation because of its simplicity and its effectiveness. In this paper, the side-branches are applied to the real pumps and the reduction effects are described. As 2nd and and harmonics of the pressure fluctuation are dominant in this pump, two side branches are used to reduce each harmonics components respectively. As a result, the vibration of wall and the interior noise of the room were suppressed violently. And it was clarified that the reduction mechanism is not resonance but the superposition of two fluctuating weves which are the progressive and reflective waves.

Investigations into human cytomegalovirus (CMV)-specific cellular immunity are important to better understand and manage CMV infections. CMV phosphoprotein pp65 is thought to be a major antigen for CMV-specific cellular immunity. We newly synthesized protein pp65 with a baculovirus expression system and purified it via metal affinity chromatography in a soluble form. The recombinant protein pp65 was antigenic in an enzyme immuno-linked assay for pp65-specific IgG in sera from 196 children. Traditional lymphoproliferation assays have shown that pp65 protein promotes specific lymphoproliferation in CMV-seropositive donors. Using an intracellular cytokine detection system, we showed that this recombinant protein stimulated CD4-positive T cells to express interferon-gamma. The results of these assays using protein pp65 were comparable with the use of CMV whole antigen. pp65- and CMV-specific cellular immunity, and CMV DNA load were also compared in four recipients of unrelated cord blood transplantation. The delay in re-constitution in CMV-specific cellular immunity was associated with reactivation of CMV. These results indicated that the recombinant protein pp65 can be used to study specific immunity in CMV infections.

The DNA of herpesviruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6 (HHV6), and human herpesvirus-7 (HHV7) has been detected in the serum of patients with primary infection or with immunosuppression. However, it is unknown how frequently herpesvirus DNA can be detected in the serum of immunocompetent children, or whether the detection of herpesvirus DNA indicates an active infection or virus-related diseases. Using a real-time polymerase chain reaction assay, attempts were made to detect herpesvirus DNA in the serum of 176 ambulatory children who visited a hospital for various reasons. EBV was detected in 4 (2.2%), HHV6 in 4 (2.2%), and HHV7 in 2 (1.1%) of 176 children, but CMV was not detected. Of the 10 positive patients, only 4 were considered, by virtue of clinical and serological characteristics, to have primary infections. The other 4 positive patients had other infections, such as mycoplasma and salmonella. Although herpesvirus DNA could be detected in the serum of immunocompetent children, there was not always a relationship between clinical manifestations and the detection of virus DNA. When herpesvirus DNA is detected in the serum, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease.

Background During the convalescent phase of acute infectious mononucleosis (AIM), Epstein-Barr virus (EBV) load shrinks rapidly in association with a rapid decline in the number of EBV-specific CD8+ T cells. The actual contribution of EBV-specific CD8+ T cells in reducing EBV load, however, is not known. Objectives To clarify the impact of EBV-specific CD8+ T cells on the contraction of EBV load in AIM, we estimated half-lives of both EBV load and EBV-specific CD8+ T cells. Study design Blood was serially taken from five pediatric patients with AIM during the convalescent period, including the very early phase, and both EBV load and EBV-specific CD8+ T cell numbers were assayed. Results EBV load declined rapidly (half-life 1.5 d) during the first 2 weeks after onset of symptoms. This half-life was seven-fold shorter than that reported for CD27+ memory B cells. Subsequently, the EBV load declined much more slowly, with a half-life of 38.7 d. EBV-specific CD8+ T cell numbers also declined concomitantly with the decrease in EBV load. The half-life of EBV-specific CD8+ T cells during first 2 weeks was 2.9 d. The number of EBV-specific CD8+ T cells and the rate of change of viral load correlated significantly (R2 ≥ 0.8; p ≤ 0.02). Conclusions The short half-life of EBV load, together with the strong correlation between the number of EBV-specific CD8+ T cells and the rate of change of viral load indicates an active role for EBV-specific CD8+ T cells in elimination of EBV in AIM.

This article describes a hypothetical model of egograms that discriminates between the orientation of the psychic energy cathected to each ego state. The first orientation is to behaviors, thoughts...

The models of motion and perception characteristics of humans are helpful to evaluate subjective efforts associated with intuitive, safe, and easy-to-use products. Traditionally, the muscle activity and/or the joint torque estimated by using a musculoskeletal model have been evaluated, whereas there are few studies that consider human's perception characteristics. In this paper, the perception characteristics of force are investigated based on the estimation of the muscle activities. Experimental analysis of human force perception characteristics in a steering wheel operation has revealed that the perceived force depends on the angle of the steering wheel and the direction of the load. This paper proposes the estimation model of the force perceived by a subject that considers human's posture- and direction-dependent perception characteristics in the steering operation. We estimate the muscle activity during the steering wheel operation by using a three-dimensional musculoskeletal model, develops a perception conversion model that follows the Weber-Fechner law, and describes the experimental results that confirm the feasibility of the proposed force perception estimation.

水溶液の状態で加温あるいは冷却すると可逆的な親・疎水転移を示す感温性ポリマーを用いた懸濁粒子の凝集について検討した. 感温性ポリマーには転位温度が約32℃のポリN-イソプロピルアクリルアミド (poly NIPAM) を用いた. 凝集試験はカオリン懸濁液を用いてジャーテスト法で行った. 操作温度がpoly NIPAMの転移温度以下の場合には, 通常の高分子凝集剤と同様に最適添加量があり, 過剰に添加するとカオリン粒子は分散安定化された. しかし, 過剰添加量の状態で転移温度以上に懸濁液を加温するとフロックの形成が認められた. さらに, これを再び転移温度以下に冷却するとフロックは分散安定化された粒子へと解体した. これらの現象から, 転位温度以上への加温によって生じるフロックの形成は粒子に吸着しているpoly NIPAM分子の疎水性相互作用によるといえる.