Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Isotope Effect on Energy Confinement Time and Thermal Transport in Neutral-Beam-Heated Stellarator-Heliotron Plasmas.

The isotope effect on energy confinement time and thermal transport has been investigated for plasmas confined by a stellarator-heliotron magnetic field. This is the first detailed assessment of an isotope effect in a stellarator heliotron. Hydrogen and deuterium plasmas heated by neutral beam injection on the Large Helical Device have exhibited no significant dependence on the isotope mass in thermal energy confinement time, which is not consistent with the simple gyro-Bohm model. A comparison of thermal diffusivity for dimensionally similar hydrogen and deuterium plasmas in terms of the gyroradius, collisionality, and thermal pressure has clearly shown robust confinement improvement in deuterium to compensate for the unfavorable mass dependence predicted by the gyro-Bohm model.

External validation of ADNEX MR SCORING system: a single-centre retrospective study.

AIM: To evaluate the accuracy of the ADNEX MR SCORING system for characterising adnexal masses. MATERIALS AND METHODS: An institutional review board approved this retrospective study. The study population comprised 663 women who underwent magnetic resonance imaging (MRI) from January 2007 to December 2014 to characterise 778 adnexal masses that were indeterminate under ultrasonography (590 benign and 188 malignant). Two radiologists independently reviewed the MRI images. The masses were scored from 1 to 5 according to the ADNEX MR SCORING system. The diagnostic performance of the system was evaluated by receiver operating characteristic (ROC) analysis. Masses scored 4 or greater were considered malignant (including tumours of borderline malignancy or low malignant potential). RESULTS: The malignancy rates of masses with scores of 2, 3, 4 and 5 were 1.9% (8/419), 12.8% (19/149), 62.6% (57/91) and 87.4% (104/119) for reader 1 and 2.1% (9/424), 13.6% (20/147), 67.6% (71/105) and 86.3% (88/102) for reader 2, respectively. The areas under the ROC curves for the differentiation of benign and malignant masses were 0.929 and 0.923, respectively; the sensitivity, specificity and accuracy of diagnosis were 85.6% (161/188), 91.7% (541/590), and 90.2% (702/778) for reader 1 and 84.6% (159/188), 91.9% (542/590), and 90.1% (701/778) for reader 2, respectively. Tumours of borderline malignancy or low malignant potential had a higher rate of misclassification (46.1%) than other malignant tumours (6-7.4%). CONCLUSION: The ADNEX MR SCORING system was highly accurate in differentiating benign and malignant adnexal masses, although it may be less accurate for tumours of borderline malignancy or low malignant potential.

Gongylonema infection of wild mammals in Japan and Sardinia (Italy).

The gullet worms, classical Gongylonema pulchrum and newly differentiated Gongylonema nepalensis, are prevalent in various mammals in Japan and Sardinia, Italy, respectively. The former species is cosmopolitan in distribution, dwelling in the mucosa of the upper digestive tract of a variety of domestic and wild mammals, and also humans. At present, the geographical distribution of G. nepalensis is known in Nepal and Sardinia, with the nematode having been recorded from the oesophagus of water buffaloes (Nepal), cattle, sheep, goats and wild mouflon (Sardinia). To clarify their natural transmission cycles among domestic and wild mammals, the present study analysed the ribosomal RNA gene (rDNA) and mitochondrial cytochrome c oxidase subunit 1 gene (cox1) of worms of various origins: G. pulchrum worms from sika deer, wild boars, Japanese macaques, and feral alien Reeves's muntjacs in Japan, and G. nepalensis worms from a red fox and a wild boar in Sardinia. Although the internal transcribed spacer (ITS) regions of rDNA and partial cox1 nucleotide sequences of G. pulchrum from native wild mammals in Japan were distinct from those of the worms in cattle, the worms from feral alien Reeves's muntjacs showed the cattle-type ITS genotype and cox1 cattle-I and II haplotypes. The rDNA and cox1 nucleotide sequences of G. nepalensis from a red fox in Sardinia were almost identical to those of the worms from domestic and wild ruminants on the island. The ecological interaction between domestic and wild mammals and their susceptibility to different Gongylonema spp. must be considered when trying to elucidate this spirurid's transmission dynamics in nature.

Suppression of Trapped Energetic Ions Driven Resistive Interchange Modes with Electron Cyclotron Heating in a Helical Plasma.

The resistive interchange mode destabilized by the resonant interaction with the trapped energetic ions is fully suppressed when the injected power of electron cyclotron heating exceeds a certain threshold. It is shown for the first time that the complete stabilization of the energetic-particle-driven mode without relaxing the energetic particle (EP) pressure gradient is possible by reducing the radial width of the eigenmodes δ_{w}, especially when δ_{w} narrows to a small enough value relative to the finite orbit width of EP.

Evaluation of the relationship between salivary concentration of anti-heat shock protein immunoglobulin and clinical manifestations of Behçet's disease.

OBJECTIVE: This study investigated the relationship between the concentration of anti-heat shock protein (HSP) 60 antibody in resting saliva and the severity of Behçet's disease (BD). METHOD: Sixty-five patients diagnosed with BD at Tokyo Medical and Dental University Hospital were enrolled in this study. Based on clinical severity scores, patients were categorized as having mild, moderate, or severe BD. Periodontal status was evaluated with the Community Periodontal Index (CPI), and anti-HSP60 antibody concentrations in resting saliva were measured with an enzyme-linked immunosorbent assay. RESULTS: The mean antibody concentration in patients in the moderate group was significantly higher than concentrations in the mild and severe groups. No significant difference was found between the mild and severe groups. Gingival inflammation, identified with the CPI, was associated with a higher antibody concentration. The antibody concentration in patients who had stomatitis for more than 2 weeks was significantly higher than in those with stomatitis for less than 2 weeks. The antibody concentration in patients who had taken colchicine was significantly lower than that in subjects who had not. CONCLUSION: These results suggest that the concentration of anti-HSP60 antibody in resting saliva may be effective as a non-invasive indicator for the diagnosis (screening) and prognostication of BD.

Resistive interchange modes destabilized by helically trapped energetic ions in a helical plasma.

A new bursting m=1/n=1 instability (m,n: poloidal and toroidal mode numbers) with rapid frequency chirping down has been observed for the first time in a helical plasma with intense perpendicular neutral beam injection. This is destabilized in the plasma peripheral region by resonant interaction between helically trapped energetic ions and the resistive interchange mode. A large radial electric field is induced near the edge due to enhanced radial transport of the trapped energetic ions by the mode, and leads to clear change in toroidal plasma flow, suppression of microturbulence, and triggering an improvement of bulk plasma confinement.

Minimal deviation endometrioid adenocarcinoma of the endometrium and its MRI findings.

Minimal deviation endometrioid adenocarcinoma (MDA-E) of the endometrium is a rare pathological entity, and its radiological features are rarely documented. A 73-year-old Japanese woman was referred to the authors when an endometrial biopsy revealed moderately differentiated endometrioid adenocarcinoma. Preoperative radiological examinations, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed no evidence of cancer nests. In the hysterectomy specimen, mildly atypical glands were scattered throughout the entire depth of the myometrium, without stromal desmoplastic reaction, and a tiny focus of typical, ruptured, endometrioid adenocarcinoma glands was found in the atrophic endometrium. MRI had not been able to identify this unusual, scattered, myometrial invasion. It should be kept in mind that in cases showing Stage IA endometrial carcinoma without endometrial thickening on MRI, this rare form of invasion may be present.

Molecular genetic conspecificity of Spiculopteragia houdemeri (Schwartz, 1926) and S. andreevae (Drózdz, 1965) (Nematoda: Ostertagiinae) from wild ruminants in Japan.

Male dimorphism of the subfamily Ostertagiinae (Nematoda: Trichostrongylidae) is a well-known phenomenon, and two or more morphotypes of a single species have previously been described as different species. Two Spiculopteragia spp., S. houdemeri (syn. S. yamashitai) and S. andreevae (syn. Rinadia andreevae) recorded in Asian cervids and wild bovids, are considered to represent major and minor morphs of S. houdemeri, respectively, based solely on their co-occurrence in the same host individual along with monomorphic females. In this study, males of morph houdemeri ( = S. houdemeri) and morph andreevae ( = S. andreevae) as well as females with three different vulval ornamentations were collected from sika deer (Cervus nippon) and Japanese serows (Capricornis crispus) distributed on the mainland of Japan. Morphologically characterized worms were subjected to molecular genetic analyses based on the internal transcribed spacer region of the ribosomal RNA gene and a partial region of the cytochrome c oxidase subunit I gene of mitochondrial DNA. Of 181 collected sika deer, 177 (97.8%) and 73 (40.3%) deer harboured males of morphs houdemeri and andreevae, respectively. Worm numbers of the former morph were found to range between 1 and 444 per individual, whereas only 1-25 worms per individual were detected for the latter morph. Five out of six serows harboured 47-71 or 2-9 males of morphs houdemeri and andreevae per individual, respectively. Females with one or two vulval flaps were predominant, but there was a substantial presence of flapless females in both host species. All the morphs of male and female adults had an identical genetic background, thus directly confirming the morphological polymorphism of S. houdemeri.

Peg1/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization.

Parthenogenesis in the mouse is embryonic lethal partly because of imprinted genes that are expressed only from the paternal genome. In a systematic screen using subtraction hybridization between cDNAs from normal and parthenogenetic embryos, we initially identified two apparently novel imprinted genes, Peg1 and Peg3. Peg1 (paternally expressed gene 1) or Mest, the first imprinted gene found on the mouse chromosome 6, may contribute to the lethality of parthenogenones and of embryos with a maternal duplication for the proximal chromosome 6. Peg1/Mest is widely expressed in mesodermal tissues and belongs to the alpha/beta hydrolase fold family. A similar approach with androgenones can be used to identify imprinted genes that are expressed from the maternal genome only.

Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein.

Genetic and embryological studies in the mouse demonstrated functional differences between parental chromosomes during development. This is due to imprinted genes whose expression is dependent on their parental origin. In a recent systematic screen for imprinted genes, we detected Peg3 (paternally expressed gene 3). Peg3 is not expressed in parthenogenones. In interspecific hybrids, only the paternal copy of the gene is expressed in the embryos, individual tissues examined in d9.5-13.5 embryos, neonates and adults. Peg3 mRNA is a 9 kb transcript encoding an unusual zinc finger protein with eleven widely spaced C2H2 type motifs and two groups of amino acid repeats. Peg3 is expressed in early somites, branchial arches and other mesodermal tissues, as well as in the hypothalamus. Peg3 maps to the proximal region of chromosome 7. Consistent with our findings, maternal duplication of the proximal chromosome 7 causes neonatal lethality. This region is syntenic with human chromosome 19q13.1-13.3 (refs 10,11), where the genes for myotonic dystrophy and a putative tumour suppressor gene are located.

Genetic variation of Gongylonema pulchrum from wild animals and cattle in Japan based on ribosomal RNA and mitochondrial cytochrome c oxidase subunit I genes.

The gullet worm (Gongylonema pulchrum) has been recorded from a variety of mammals worldwide, including monkeys and humans. Due to its wide host range, it has been suggested that the worm may be transmitted locally to any mammalian host by chance. To investigate this notion, the ribosomal RNA gene (rDNA), mainly regions of the internal transcribed spacers (ITS) 1 and 2, and a cytochrome c oxidase subunit I (COI) region of mitochondrial DNA of G. pulchrum were characterized using parasites from the following hosts located in Japan: cattle, sika deer, wild boars, Japanese macaques, a feral Reeves's muntjac and captive squirrel monkeys. The rDNA nucleotide sequences of G. pulchrum were generally well conserved regardless of their host origin. However, a few insertions/deletions of nucleotides along with a few base substitutions in the ITS1 and ITS2 regions were observed in G. pulchrum from sika deer, wild boars and Japanese macaques, and those differed from G. pulchrum in cattle, the feral Reeves's muntjac and captive squirrel monkeys. The COI sequences of G. pulchrum were further divided into multiple haplotypes and two groups of haplotypes, i.e. those from a majority of sika deer, wild boars and Japanese macaques and those from cattle and zoo animals, were clearly differentiated. Our findings indicate that domestic and sylvatic transmission cycles of the gullet worm are currently present, at least in Japan.

Role of raising the upper limb of the non-rising side when performing rising movements from bed.

Rising movements from bed comprise an important aspect of recovery from the bedridden state; however, they have not been sufficiently investigated using motion analysis studies. In particular, the effect of using the upper limb of the non-rising side before waist flexion on rising movements remains to be analyzed; this study aimed to clarify this effect. Accordingly, motion analyses were performed on rising movements under two constraint conditions, namely raising the upper limb of the non-rising side (upper limb use-condition) and keeping it in contact with the pelvis (upper limb non-use-condition); subsequently, the kinematics and kinematics parameters were compared. In comparison with the upper limb use-condition, in the upper limb non-use-condition, the distance traveled by the center of mass of the body (CoM trajectory, p < 0.01) increased while switching from the half-side-lying to on-hand postures, horizontal body movement (movement speed (Normalized time/total time), p < 0.01 and weight of center of body mass (CoM momentum in horizontal plane), p < 0.05) during the same period increased, and the half-side-lying time approached the peak value of the waist flexion angular velocity (Time lag between from half-side-lying to waist angler peak velocity, p < 0.05). The compensatory movement that occurred due to the upper limb non-use-condition denoted an increase in body momentum in the horizontal direction, rather than in the sagittal plane. Therefore, the upper limb on the non-rising side contributed to the smooth movement of the body in the horizontal direction. Moreover, this study demonstrated that asymmetrical rising movement in the diagonal direction is a characteristic movement wherein the horizontal movement of the body constitutes the main movement.

Development of a nomogram incorporating serum C-reactive protein level to predict overall survival of patients with advanced urothelial carcinoma and its evaluation by decision curve analysis.

BACKGROUND: The purpose of this study is to investigate the prognostic impact of C-reactive protein (CRP) on patients with advanced urothelial carcinoma and to develop a novel nomogram predicting survival. METHODS: A total of 223 consecutive patients were treated at Tokyo Medical and Dental Hospital. A nomogram incorporating V was developed based on the result of a Cox proportional hazards model. Its efficacy and clinical usefulness was evaluated by concordance index (c-index) and decision curve analysis. RESULTS: Of the 223 patients, 184 (83%) died of cancer. Median follow-up periods of patients who died and those who remained alive were 5 and 11 months, respectively. We developed a novel nomogram incorporating Eastern Cooperative Oncology Group Performance Status, presence of visceral metastasis, haemoglobin and age. The c-index of the nomogram predicting survival probability 6 and 12 months after diagnosis was 0.788 and 0.765, respectively. Decision curve analyses revealed that the novel nomogram incorporating CRP had a superior net benefit than that without CRP for most of the examined probabilities. CONCLUSION: We demonstrated the prognostic impact of CRP that improved the predictive accuracy of a nomogram for survival probability in patients with advanced urothelial carcinoma.

Peptidoglycan and lipopolysaccharide synergistically enhance bone resorption and osteoclastogenesis.

BACKGROUND AND OBJECTIVE: Peptidoglycan (PGN) and lipopolysaccharide (LPS) are bacterial cell wall constituents that are able to induce bone resorption by stimulating Toll-like receptor (TLR) 2 and TLR4, respectively. The fragments of PGN also stimulate inflammatory responses via nucleotide-binding oligomerization domain (NOD) 1 and NOD2, although there are differences in the NOD-stimulatory activities between gram-positive and gram-negative PGNs. The TLR and NOD signaling pathways are known to engage in cross-talk to enhance the production of inflammatory cytokines. In the present study, we investigated the effects of gram-negative and gram-positive PGNs on bone resorption and osteoclastogenesis in the presence or absence of LPS. MATERIAL AND METHODS: We injected Escherichia coli PGN or Staphylococcus aureus PGN with or without LPS into mouse gingiva, and histopathologically assessed alveolar bone resorption by tartrate-resistant acid phosphatase staining. We also stimulated osteoclast precursors from mouse bone marrow macrophages with these PGNs in vitro and assessed osteoclastogenesis. The cells were also stimulated with synthetic ligands for NOD1; γ-D-glutamyl-meso-DAP NOD2; muramyl dipeptide or TLR2; Pam(3) CSK(4) with or without LPS to analyse the signaling cross-talk. RESULTS: S. aureus PGN, but not E. coli PGN, induced alveolar bone resorption, as did LPS. However, PGN from both sources significantly enhanced the bone resorption in the mice co-injected with LPS. Both types of PGNs induced osteoclastogenesis and accelerated osteoclastogenesis when the cells were co-stimulated with LPS in vitro. All synthetic ligands synergistically induced osteoclastogenesis by co-stimulation with LPS. CONCLUSION: Gram-positive or gram-negative PGN worked synergistically with LPS to induce bone resorption and osteoclastogenesis, possibly by co-ordinating the effects of TLR2, NOD1, NOD2 and TLR4 signaling.

Locally administered interferon-γ accelerates lipopolysaccharide-induced osteoclastogenesis independent of immunohistological RANKL upregulation.

BACKGROUND AND OBJECTIVE: Interferon-γ (IFN-γ) potently inhibits RANKL-induced osteoclastogenesis in vitro. In contrast, previous studies have shown that an increase in IFN-γ expression is correlated with an increase in lipopolysaccharide (LPS)-induced bone loss in vivo. However, it is not clear whether local IFN-γ accelerates osteoclastogenesis or not in vivo. Therefore, the aim of this study was to clarify the role of local IFN-γ in LPS-induced osteoclastogenesis. MATERIALS AND METHODS: We induced bone loss in calvaria by injecting LPS. One group of mice received an IFN-γ injection together with LPS injection, while another group received IFN-γ 2 d after LPS injection. Bone resorption was observed histologically. Next, we stimulated murine bone marrow macrophages with macrophage-colony stimulating factor and RANKL in vitro. We added different doses of IFN-γ and/or LPS at 0 or 48 h time points. Cells were stained with tartrate-resistant acid phosphatase at 72 h. RESULTS: Local administration of IFN-γ together with LPS injection did not affect osteoclast formation. However, IFN-γ injected after LPS injection accelerated osteoclast formation. Also, we confirmed that IFN-γ added at 0 h inhibited RANKL-induced osteoclastogenesis in vitro. However, inhibition by IFN-γ added at 48 h was reduced compared with that by IFN-γ added at 0 h. Interestingly, IFN-γ together with a low concentration of LPS accelerated osteoclast formation when both were added at 48 h compared with no addition of IFN-γ. CONCLUSION: The results suggest that local IFN-γ accelerates osteoclastogenesis in certain conditions of LPS-induced inflammatory bone loss.

Membrane-bound CD40 ligand on T cells from mice injected with lipopolysaccharide accelerates lipopolysaccharide-induced osteoclastogenesis.

BACKGROUND AND OBJECTIVE: T cells infiltrate the inflammatory site of periodontitis and consequently stimulate the loss of periodontal bone. We previously reported that T cells from lipopolysaccharide (LPS)-injected mice (LPS-T cells) accelerated osteoclastogenesis in the presence of LPS. Ηowever, the detailed mechanism of this acceleration is still unclear. In this study, we analyzed the mechanism of osteoclastogenesis accelerated by LPS-T cells. MATERIAL AND METHODS: We examined the mechanism of osteoclastogenesis acceleration. First, to determine the effect of cell-to-cell contact, we co-cultured T cells and bone marrow macrophages, prestimulated with RANKL for 48 h (R-BMMs), in the presence of LPS for 24 h, in a Transwell. Second, to determine the effect of CD40 ligand (CD40L), we co-cultured T cells and R-BMMs in the presence of LPS and anti-CD40L immunoglobulin. Third, we examined the effect of recombinant mouse CD40L (rCD40L) in the presence of LPS in vitro and in vivo. Lastly, we examined the expression of membrane-bound CD40L (mCD40L) by fluorescence-activated cell sorting (FACS). RESULTS: Blocking cell-to-cell contact between LPS-T cells and R-BMMs completely inhibited the acceleration of osteoclastogenesis. Anti-CD40L immunoglobulin also completely inhibited the acceleration of osteoclastogenesis. Moreover, rCD40L accelerated osteoclastogenesis in the presence of LPS in vitro and in vivo. Finally, the expression of mCD40L on LPS-T cells was higher than that on T cells isolated from mice not injected with LPS. CONCLUSION: The results demonstrate that CD40L accelerates osteoclastogenesis in the presence of RANKL and LPS. The results also suggest that mCD40L on LPS-T cells accelerates osteoclastogenesis.

Usefulness of Muscle Synergy Analysis in Individuals With Knee Osteoarthritis During Gait.

OBJECTIVE: To clarify whether there are any muscle synergy changes in individuals with knee osteoarthritis, and to determine whether muscle synergy analysis could be applied to other musculoskeletal diseases. METHODS: Subjects in this study included 11 young controls (YC), 10 elderly controls (EC), and 10 knee osteoarthritis patients (KOA). Gait was assessed on a split-belt treadmill at 3 km/h. A non-negative matrix factorization (NNMF) was applied to the electromyogram data matrix to extract muscle synergies. To assess the similarity of each module, we performed the NNMF analysis assuming four modules for all of the participants. Further, we calculated joint angles to compare the kinematic data between the module groups. RESULTS: The number of muscle modules was significantly lower in the EC (2-3) and KOA (2-3) groups than in the YC group (3-4), which reflects the merging of late swing and early stance modules. The EC and KOA groups also showed greater knee flexion angles in the early stance phase. Contrarily, by focusing on the module structure, we found that the merging of early and late stance modules is characteristic in KOA. CONCLUSION: The lower number of modules in the EC and KOA groups was due to the muscle co-contraction with increased knee flexion angle. Contrarily, the merging of early and late stance modules are modular structures specific to KOA and may be biomarkers for detecting KOA. SIGNIFICANCE: Describing the changes in multiple muscle control associated with musculoskeletal degeneration can serve as a fundamental biomarker in joint disease.

Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy.

BACKGROUND: A recent laboratory study indicated that statins impaired the antitumor effects of rituximab by inducing conformational changes in CD20. Although these findings raised significant concerns about statin use during rituximab treatment, their clinical significance is unclear. PATIENTS AND METHODS: We conducted a retrospective study investigating the effects of statins on the prognosis of diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Newly diagnosed DLBCL patients were analyzed (n = 256), including 35 patients taking statins. RESULTS: The 3-year progression-free survival rates were 84% and 73% (P = 0.38), while the overall survival rates were 89% and 78% (P = 0.28) for those patients treated with and without statins, respectively. After adjusting for the International Prognostic Index and serum cholesterol level, statin use was not associated with prognosis. CONCLUSIONS: These results indicate that statins do not influence the clinical prognosis of DLBCL treated with RCHOP. Further studies with larger numbers of patients are warranted to confirm the prognostic significance of statins for patients with DLBCL receiving rituximab-containing chemotherapy.

Bone metastasis and poor performance status are prognostic factors for survival of carcinoma of unknown primary site in patients treated with systematic chemotherapy.

BACKGROUND: Cancer of unknown primary site (CUP) generally has a poor prognosis, and there is no established standard therapy. There have been no reports of a prognostic model for CUP patients treated with a single regimen of systemic chemotherapy. METHODS: Univariate and multivariate prognostic factor analysis for overall survival (OS) were conducted retrospectively in 58 consecutive CUP patients treated with carboplatin plus paclitaxel (Taxol) therapy as a first-line treatment. RESULTS: Univariate prognostic factor analysis revealed baseline performance status (PS) of two or more, low serum albumin level, pleural effusion, bone metastasis, and liver metastasis as adverse prognostic factors. Cox proportional hazards analysis showed that poor PS and bone metastasis had the most powerful adverse impact on survival. We developed a prognostic model using those two variables-a good-risk group (PS 0-1 without bone metastasis) and a poor-risk group (PS > or =2 or bone metastasis). The poor-risk group showed significantly poorer OS than the good-risk group (1 year OS 36.8% versus 67.1%, P = 0.0003). CONCLUSIONS: Poor PS and bone metastasis were identified as independent adverse prognostic factors in CUP. A simple prognostic model was developed and seems useful for decision making as to whether chemotherapy is indicated for CUP patients.