Impacts of workplace verbal aggression classified via text mining on workers' mental health.

BACKGROUND: Exposure to workplace aggression adversely affects workers' health; however, little is known regarding the impact of specific types of verbal content. AIMS: We aimed to examine the relationship between exposure to several types of aggressive words at work and the victim's depressive symptoms and sleep disturbance using text mining. METHODS: We conducted a longitudinal survey with 800 workers in wholesale and retail companies; of which, 500 responded to the follow-up survey. The Centre for Epidemiologic Studies-Depression Scale and Pittsburgh Sleep Quality Index were filled out by the participants, and their responses were analysed by logistic regression to evaluate the risk of depression or sleep problems. We collected exact aggressive words encountered at work over the past year as a dependent variable and classified it into four types using text mining, such as words criticizing one's performance. RESULTS: The follow-up rate was 63%. Exposure to words threatening one's life showed a significant relationship with the risk of depression (odds ratio [OR] = 13.94, 95% confidence interval [CI] = 1.76-110.56). The exposure to words criticizing one's job performance is significantly related to the risk of sleep disturbance (OR = 5.56, 95% CI = 2.08-14.88). CONCLUSIONS: These findings suggest that different contents of verbal aggression can have different impacts on workers' health. This indicates that not only overtly threatening and abusive language but also words related to one's performance can be a risk factor for workers, depending on how they are delivered. To mitigate the adverse effects, promoting effective communication and cultivating psychological detachment from work may be beneficial.

Relative contributions of large-scale and wedgelet currents in the substorm current wedge.

We examined how much large-scale and localized upward and downward currents contribute to the substorm current wedge (SCW), and how they evolve over time, using the THEMIS all-sky imagers (ASIs) and ground magnetometers. One type of events is dominated by a single large-scale wedge, with upward currents over the surge and broad downward currents poleward-eastward of the surge. The other type of events is a composite of large-scale wedge and wedgelets associated with streamers, with each wedgelet having comparable intensity to the large-scale wedge currents. Among 17 auroral substorms with wide ASI coverage, the composite current type is more frequent than the single large-scale wedge type. The dawn-dusk size of each wedgelet is ~ 600 km in the ionosphere (~ 3.2 R E in the magnetotail, comparable to the flow channel size). We suggest that substorms have more than one type of SCW, and the composite current type is more frequent.

Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701).

Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

The comparison of nasal surgery and CPAP on daytime sleepiness in patients with OSAS.

OBJECTIVE: Residual sleepiness after continuous positive airway pressure (CPAP) is a critical problem in some patients with obstructive sleep apnea syndrome (OSAS). However, nasal surgery is likely to reduce daytime sleepiness and feelings of unrefreshed sleep. The aim of this study is to clarify the effects of nasal surgery and CPAP on daytime sleepiness. METHODOLOGY: This is a retrospective and matched-case control study. The participants were consecutive 40 patients with OSAS who underwent nasal surgery (Surgery group) and 40 matched patients who were treated with CPAP (CPAP group). RESULTS: In the Surgery group, although the nasal surgery did not decrease either apnea or hypopnea, it improved oxygenation, the quality of sleep. In the CPAP Group, the CPAP treatment reduced apnea and hypopnea, and improved oxygenation, quality of sleep. The degree of relief from daytime sleepiness was different between the two groups. The improvement of Epworth Sleepiness Scale was more significant in the Surgery Group than those in the CPAP Group (Surgery from 11.0 to 5.1, CPAP from 10.0 to 6.2). DISCUSSION: These findings suggest that the results of the nasal surgery is more satisfactory for some patients with OSAS than CPAP on daytime sleepiness.

Fast Heating of Imploded Core with Counterbeam Configuration.

A tailored-pulse-imploded core with a diameter of 70 µm is flashed by counterirradiating 110 fs, 7 TW laser pulses. Photon emission (>40 eV) from the core exceeds the emission from the imploded core by 6 times, even though the heating pulse energies are only one seventh of the implosion energy. The coupling efficiency from the heating laser to the core using counterirradiation is 14% from the enhancement of photon emission. Neutrons are also produced by counterpropagating fast deuterons accelerated by the photon pressure of the heating pulses. A collisional two-dimensional particle-in-cell simulation reveals that the collisionless two counterpropagating fast-electron currents induce mega-Gauss magnetic filaments in the center of the core due to the Weibel instability. The counterpropagating fast-electron currents are absolutely unstable and independent of the core density and resistivity. Fast electrons with energy below a few MeV are trapped by these filaments in the core region, inducing an additional coupling. This might lead to the observed bright photon emissions.

Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR.

Rare maternally inherited duplications at 15q11-13 are observed in ~1% of individuals with an autism spectrum disorder (ASD), making it among the most common causes of ASD. 15q11-13 comprises a complex region, and as this copy number variation encompasses many genes, it is important to explore individual genotype-phenotype relationships. Cytoplasmic FMR1-interacting protein 1 (CYFIP1) is of particular interest because of its interaction with Fragile X mental retardation protein (FMRP), its upregulation in transformed lymphoblastoid cell lines from patients with duplications at 15q11-13 and ASD and the presence of smaller overlapping deletions of CYFIP1 in patients with schizophrenia and intellectual disability. Here, we confirm that CYFIP1 is upregulated in transformed lymphoblastoid cell lines and demonstrate its upregulation in the post-mortem brain from 15q11-13 duplication patients for the first time. To investigate how increased CYFIP1 dosage might predispose to neurodevelopmental disease, we studied the consequence of its overexpression in multiple systems. We show that overexpression of CYFIP1 results in morphological abnormalities including cellular hypertrophy in SY5Y cells and differentiated mouse neuronal progenitors. We validate these results in vivo by generating a BAC transgenic mouse, which overexpresses Cyfip1 under the endogenous promotor, observing an increase in the proportion of mature dendritic spines and dendritic spine density. Gene expression profiling on embryonic day 15 suggested the dysregulation of mammalian target of rapamycin (mTOR) signaling, which was confirmed at the protein level. Importantly, similar evidence of mTOR-related dysregulation was seen in brains from 15q11-13 duplication patients with ASD. Finally, treatment of differentiated mouse neuronal progenitors with an mTOR inhibitor (rapamycin) rescued the morphological abnormalities resulting from CYFIP1 overexpression. Together, these data show that CYFIP1 overexpression results in specific cellular phenotypes and implicate modulation by mTOR signaling, further emphasizing its role as a potential convergent pathway in some forms of ASD.

Scaling up nano-milling of poorly water soluble compounds using a rotation/revolution pulverizer.

We previously reported that a rotation/revolution pulverizer (NP-100) could mill a small amount of a drug (0.1 g) into nanoparticles in several minutes. In this investigation, scale up from the milligram to the kilogram scale of the nano-milling process by the rotation/revolution pulverizer was studied. Phenytoin was used as a model drug with low solubility in water. After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP-100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T). A theoretical equation for the specific collisional energy was adapted for wet milling; this suggested that the relative centrifugal acceleration of revolution (revolution G) and the drug concentration in the suspension were the two most important parameters. The results obtained using NP-100 and ARV-3000T correlated well when these two parameters were identical. These results were applied to the large scale model of NP-100 (ARV-10KT), where 2 kg (1 kg x 2) of phenytoin nanoparticles were obtained in 60 min. The results from PXRD and DSC indicated that the milled phenytoin by ARV-3000T and ARV-10KT maintained its crystallinity. These results suggest nano-milling using a rotation/revolution pulverizer will be widely applicable to the development of nano-medicine.

Overexpression of SMYD2 contributes to malignant outcome in gastric cancer.

BACKGROUND: SET and MYND domain-containing protein 2 (SMYD2) is a lysine methyltransferase for histone H3, p53 and Rb and inhibits their transactivation activities. In this study, we tested whether SMYD2 (1q42) acts as a cancer-promoting factor by being overexpressed in gastric cancer. METHODS: We analysed 7 gastric cancer cell lines and 147 primary tumor samples of gastric cancer, which were curatively resected in our hospital. RESULTS: SET and MYND domain-containing protein 2 was detected in these cell lines (five out of seven cell lines; 71.4%) and primary tumor samples (fifty-six out of one hundred and forty-seven cases; 38.1%). Knockdown of SMYD2 using specific small interfering RNA inhibited proliferation, migration and invasion of SMYD2-overexpressing cells in a TP53 mutation-independent manner. Overexpression of SMYD2 protein correlated with larger tumor size, more aggressive lymphatic invasion, deeper tumor invasion and higher rates of lymph node metastasis and recurrence. Patients with SMYD2-overexpressing tumours had a worse overall rate of survival than those with non-expressing tumours (P=0.0073, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SMYD2 was independently associated with worse outcome (P=0.0021, hazard ratio 4.25 (1.69-10.7)). CONCLUSIONS: These findings suggest that SMYD2 has a crucial role in tumor cell proliferation by its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer.

Direct heating of a laser-imploded core by ultraintense laser-driven ions.

A novel direct core heating fusion process is introduced, in which a preimploded core is predominantly heated by energetic ions driven by LFEX, an extremely energetic ultrashort pulse laser. Consequently, we have observed the D(d,n)^{3}He-reacted neutrons (DD beam-fusion neutrons) with the yield of 5×10^{8} n/4π sr. Examination of the beam-fusion neutrons verified that the ions directly collide with the core plasma. While the hot electrons heat the whole core volume, the energetic ions deposit their energies locally in the core, forming hot spots for fuel ignition. As evidenced in the spectrum, the process simultaneously excited thermal neutrons with the yield of 6×10^{7} n/4π sr, raising the local core temperature from 0.8 to 1.8 keV. A one-dimensional hydrocode STAR 1D explains the shell implosion dynamics including the beam fusion and thermal fusion initiated by fast deuterons and carbon ions. A two-dimensional collisional particle-in-cell code predicts the core heating due to resistive processes driven by hot electrons, and also the generation of fast ions, which could be an additional heating source when they reach the core. Since the core density is limited to 2 g/cm^{3} in the current experiment, neither hot electrons nor fast ions can efficiently deposit their energy and the neutron yield remains low. In future work, we will achieve the higher core density (>10 g/cm^{3}); then hot electrons could contribute more to the core heating via drag heating. Together with hot electrons, the ion contribution to fast ignition is indispensable for realizing high-gain fusion. By virtue of its core heating and ignition, the proposed scheme can potentially achieve high gain fusion.

Search for Nucleon and Dinucleon Decays with an Invisible Particle and a Charged Lepton in the Final State at the Super-Kamiokande Experiment.

Search results for nucleon decays p→e^{+}X, p→µ^{+}X, n→νγ (where X is an invisible, massless particle) as well as dinucleon decays np→e^{+}ν, np→µ^{+}ν, and np→τ^{+}ν in the Super-Kamiokande experiment are presented. Using single-ring data from an exposure of 273.4 kton·yr, a search for these decays yields a result consistent with no signal. Accordingly, lower limits on the partial lifetimes of τ_{p→e^{+}X}>7.9×10^{32} yr, τ_{p→µ^{+}X}>4.1×10^{32} yr, τ_{n→νγ}>5.5×10^{32} yr, τ_{np→e^{+}ν}>2.6×10^{32} yr, τ_{np→µ^{+}ν}>2.2×10^{32} yr, and τ_{np→τ^{+}ν}>2.9×10^{31} yr at a 90% confidence level are obtained. Some of these searches are novel.

Search for neutrinos from annihilation of captured low-mass dark matter particles in the sun by super-kamiokande.

Super-Kamiokande (SK) can search for weakly interacting massive particles (WIMPs) by detecting neutrinos produced from WIMP annihilations occurring inside the Sun. In this analysis, we include neutrino events with interaction vertices in the detector in addition to upward-going muons produced in the surrounding rock. Compared to the previous result, which used the upward-going muons only, the signal acceptances for light (few-GeV/c^{2}-200-GeV/c^{2}) WIMPs are significantly increased. We fit 3903 days of SK data to search for the contribution of neutrinos from WIMP annihilation in the Sun. We found no significant excess over expected atmospheric-neutrino background and the result is interpreted in terms of upper limits on WIMP-nucleon elastic scattering cross sections under different assumptions about the annihilation channel. We set the current best limits on the spin-dependent WIMP-proton cross section for WIMP masses below 200 GeV/c^{2} (at 10 GeV/c^{2}, 1.49×10^{-39} cm^{2} for χχ→bb[over ¯] and 1.31×10^{-40} cm^{2} for χχ→τ^{+}τ^{-} annihilation channels), also ruling out some fraction of WIMP candidates with spin-independent coupling in the few-GeV/c^{2} mass range.

Construction and molecular characterization of a T-cell receptor-like antibody and CAR-T cells specific for minor histocompatibility antigen HA-1H.

The genetic transfer of T-cell receptors (TCRs) directed toward target antigens into T lymphocytes has been used to generate antitumor T cells efficiently without the need for the in vitro induction and expansion of T cells with cognate specificity. Alternatively, T cells have been gene-modified with a TCR-like antibody or chimeric antigen receptor (CAR). We show that immunization of HLA-A2 transgenic mice with tetramerized recombinant HLA-A2 incorporating HA-1 H minor histocompatibility antigen (mHag) peptides and ß2-microglobulin (HA-1 H/HLA-A2) generate highly specific antibodies. One single-chain variable region moiety (scFv) antibody, #131, demonstrated high affinity (KD=14.9 nM) for the HA-1 H/HLA-A2 complex. Primary human T cells transduced with #131 scFV coupled to CD28 transmembrane and CD3ζ domains were stained with HA-1 H/HLA-A2 tetramers slightly more intensely than a cytotoxic T lymphocyte (CTL) clone specific for endogenously HLA-A2- and HA-1 H-positive cells. Although #131 scFv CAR-T cells required >100-fold higher antigen density to exert cytotoxicity compared with the cognate CTL clone, they could produce inflammatory cytokines against cells expressing HLA-A2 and HA-1 H transgenes. These data implicate that T cells with high-affinity antigen receptors reduce the ability to lyse targets with low-density peptide/MHC complexes (~100 per cell), while they could respond at cytokine production level.

Downregulation of Max dimerization protein 3 is involved in decreased visceral adipose tissue by inhibiting adipocyte differentiation in zebrafish and mice.

BACKGROUND: The diet-induced obesity model of zebrafish (DIO-zebrafish) share a common pathophysiological pathway with mammalian obesity. OBJECTIVES: We aimed to investigate the role of Max dimerization protein 3 (MXD3) in visceral fat accumulation and adipocyte differentiation, by conducting knockdown experiments using zebrafish and mouse preadipocytes. METHODS: To identify genes related to visceral adiposity, we conducted transcriptome analyses of human and zebrafish obese populations using the Gene Expression Omnibus and DNA microarray. We then intraperitoneally injected morpholino antisense oligonucleotides (MO-mxd3) to knockdown mxd3 gene expression in DIO-zebrafish and measured several parameters, which reflected human obesity and associated metabolic diseases. Finally, lentiviral Mxd3 shRNA knockdown in mouse 3T3-L1 preadipocytes was conducted. Quantitative PCR analyses of several differentiation markers were conducted during these gene knockdown experiments. RESULTS: We found that MXD3 expression was increased in the obese population in humans and zebrafish. Intraperitoneal MO-mxd3 administration to DIO-zebrafish suppressed the increase in body weight, visceral fat accumulation and the size of mature adipocytes. Subsequently, dyslipidemia and liver steatosis were also ameliorated by MO-mxd3. In mouse adipocytes, Mxd3 expression was drastically increased in the early differentiation stage. Mxd3 shRNA inhibited preadipocyte proliferation and adipocyte maturation. Quantitative PCR analyses showed that the early differentiation marker, CCAAT/enhancer-binding protein delta (Cebpd) and late differentiation markers (CCAAT/enhancer-binding protein, alpha and peroxisome proliferator-activated receptor gamma) were downregulated by Mxd3 knockdown in 3T3-L1 cells and DIO-zebrafish. Subsequently, mature adipocyte markers (adiponectin and caveolin 1 for zebrafish, and fatty acid binding protein 4 and stearoyl-coenzyme A desaturase 1 for mouse adipocytes) were also decreased. CONCLUSION: Mxd3 regulates preadipocyte proliferation and early adipocyte differentiation via Cebpd downregulation in vitro and in vivo. Integrated analysis of human and zebrafish transcriptomes allows identification of a novel therapeutic target against human obesity and further associated metabolic disease.

Search for trilepton nucleon decay via p→e+νν and p→µ+νν in the Super-Kamiokande experiment.

The trilepton nucleon decay modes p→e+νν and p→µ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τp→e+νν>1.7×10(32) years and τp→µ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.

First indication of terrestrial matter effects on solar neutrino oscillation.

We report an indication that the elastic scattering rate of solar B8 neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through Earth during nighttime. We determine the day-night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be [-3.2 ± 1.1(stat) ± 0.5(syst)]%, which deviates from zero by 2.7 σ. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a nonzero day-night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day-night asymmetry is consistent with neutrino oscillations for 4 × 10(-5) eV(2) ≤ Δm 2(21) ≤ 7 × 10(-5) eV(2) and large mixing values of θ12, at the 68% C.L.

Discussion based on analysis of the suicide rate and the average disposable income per household in Japan.

OBJECTIVE: Suicide is one of the major social issues in Japan. According to a report of the National Policy Agency, there were approximately 22 000 to 24 000 annual suicides between 1994 and 1997 and there have been over 30 000 annual suicides in Japan since 1998. For these reasons, we think it is important to discuss the economic factor related to suicides in recent years. METHOD: In this study, we examined suicide rates and the average disposable income per household in Japan in the last 15 years (ie 1994-2008) and discuss the statistical analysis of the average disposable income per household and the associated suicide rates. RESULTS AND DISCUSSION: During the research period, annual suicide rates per 100 000 population in Japan ranged from 16.9 to 25.5 among the total population, from 23.1 to 38.0 among men, and from 10.9 to 14.7 among women. The annual average disposable income per household (ten thousand yen) ranged from 424.0 to 549.9. The average disposable income per household was related to the suicide rate among the total population and among men. The average disposable income per household was not related to the suicide rate among women. CONCLUSION: We believe that this discussion will be useful in developing specific suicide preventive measures.

Clinical and Surgical Outcomes of Endoscopic Endonasal Approach for Giant Pituitary Adenomas: Analysis of Predictive Factors.

BACKGROUND: Giant pituitary adenomas (GPAs) are defined as tumors with ≥40 mm in any maximum diameter, and these tend to invade multiple intracranial compartments. Hence, treatment remains a surgical challenge. OBJECTIVE: To describe the clinical and surgical outcomes of the endoscopic endonasal approach (EEA) for GPA in a pituitary referral center in Latin America and to analyze associated predictive factors. METHODS: 37 patients with histologically-confirmed GPA treated solely through the EEA between a 2-year period were included. Preoperative and postoperative clinical and neuroimaging findings; surgical morbidity and mortality; and binary logistic regression analysis to assess predictive factors were analyzed. RESULTS: Preoperative visual impairment prevalence was 97.3%. Mean tumor volume was 32 cc and gross total resection rate was 40.5%. Favorable visual acuity and visual fields outcome rate was 75% and 82.9%, respectively. In the multivariate analysis, bilateral cavernous sinus invasion (P = 0.018) and postoperative cerebrospinal fluid (CSF) leak (P = 0.036) were associated with an unfavorable visual acuity outcome, while radiation therapy (P = 0.035) was for visual fields. Similarly, intraoperative CSF leak was a predictive factor for postoperative CSF leak (10.8%) (P = 0.042) and vascular injury (13.5%) (P = 0.048). CONCLUSIONS: In this first Mexican clinical series, we demonstrated that the EEA is a safe and effective technique for GPA, although early diagnosis and prompt intervention may promote further visual function preservation without significant endocrine morbidity.

TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells.

We previously reported a method to generate dendritic cell (DC)-like antigen-presenting cells (APC) from human induced pluripotent stem (iPS) cells. However, the method is relatively complicated and laborious. In the current study, we attempted to establish a method through which we could obtain a large number of functional APC with a simple procedure. We transduced iPS cell-derived CD11b(+) myeloid cells with genes associated with proliferative or anti-senescence effects, enabling the cells to propagate for more than 4 months in a macrophage colony-stimulating factor (M-CSF)-dependent manner while retaining their capacity to differentiate into functional APC. We named these iPS cell-derived proliferating myeloid cells 'iPS-ML', and the iPS-ML-derived APC 'ML-DC'. In addition, we generated TAP2-deficient iPS cell clones by zinc finger nuclease-aided targeted gene disruption. TAP2-deficient iPS cells and iPS-ML avoided recognition by pre-activated allo-reactive CD8(+) T cells. TAP2-deficient ML-DC expressing exogenously introduced HLA-A2 genes stimulated HLA-A2-restricted MART-1-specific CD8(+) T cells obtained from HLA-A2-positive allogeneic donors, resulting in generation of MART-1-specific cytotoxic T lymphocyte (CTL) lines. TAP-deficient iPS-ML introduced with various HLA class I genes may serve as an unlimited source of APC for vaccination therapy. If administered into allogeneic patients, ML-DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and, after that, be completely eliminated. Based on the present study, we propose an APC-producing system that is simple, safe and applicable to all patients irrespective of their HLA types.