Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

Estimation of the relationship between the thermal environment of a house in winter and its occupants' health.

This study aims to quantify the relationship between the arbitrary thermal environment of houses in winter and their occupants' health through a comprehensive questionnaire survey, involving approximately 24,000 individuals who moved into insulated dwellings in Japan. A relationship between the degree of the thermal insulation of these houses and corresponding rates of improvement in the following 10 diseases were formulated: heart disease, cerebrovascular disease, hypertension, diabetes mellitus, asthma, dermatitis and eczema, pneumonia, inflammatory polyarthropathies, allergic rhinitis, and conjunctivitis. Following the statistical analysis of these outcomes, significant differences in improvement rates were identified among the levels of the thermal insulation of houses for the following five diseases: cerebrovascular diseases, asthma, dermatitis and eczema, allergic rhinitis, and conjunctivitis. In addition, the thermal environments of houses corresponding to each thermal insulation level were estimated by numerical simulations. Using these results, we organized the relationships between the thermal environment conditions of houses and observed prevalence rate for the following four diseases for which the improvement rates increased with increasing insulation levels and significant differences were identified: asthma, dermatitis and eczema, allergic rhinitis, and conjunctivitis. Consequently, we formulated equations to predict the prevalence rates of these diseases using the "mean operative temperature of rooms occupied by each family member from January 1 to February 28."

Sintering Metal-Organic Framework Gels for Application as Structural Adhesives.

Metal-organic frameworks (MOFs)/coordination polymers are promising materials for gas separation, fuel storage, catalysis, and biopharmaceuticals. However, most applied research on MOFs is limited to these functional materials thus far. This study focuses on the potential of MOFs as structural adhesives. A sintering technique is applied to a zeolitic imidazolate framework-67 (ZIF-67) gel that enables the joining of Cu substrates, resulting in a shear strength of over 30 MPa, which is comparable to that of conventional structural adhesives. Additionally, systematic experiments are performed to evaluate the effects of temperature and pressure on adhesion, indicating that the removal of excess 2-methylimidazole and the by-product (acetic acid) from the sintered material by vaporization results in a microstructure composed of large spherical ZIF-67 crystals that are densely aggregated, which is essential for achieving a high shear strength.

Association between tumor response to systemic therapy and patient-reported disease symptoms.

BACKGROUND: The association of treatment-induced tumor shrinkage with symptom palliation for patients with lung cancer remains unknown. We investigated this correlation using the Edmonton Symptom Assessment System-Revised. METHODS: Using the in-hospital cancer registry, we identified patients receiving chemotherapy and/or immunotherapy for newly diagnosed advanced or metastatic lung cancer. Tumor response and post-treatment Edmonton Symptom Assessment System-Revised were obtained after 2-3 treatment cycles. Patients were divided into groups with or without >30% unidirectional tumor shrinkage (objective response [OR] or non-OR [N-OR] groups, respectively). They were further classified as good-objective response (>50% unidirectional tumor shrinkage), moderate-objective response (30-50% shrinkage), progressive disease (>20% tumor growth or new lesion) or stable disease (SD; N-objective response and non-progressive disease). The primary endpoint was change in the total Edmonton Symptom Assessment System-Revised score from baseline. The Mann-Whitney U test was used for analysis. RESULTS: In total, 113 patients were enrolled. The total Edmonton Symptom Assessment System-Revised score was significantly more improved in the OR group versus the N-OR group (median: 5 vs. 2, respectively; P = 0.013). This association was more prominent in patients with small-cell lung cancer and large-cell neuroendocrine tumor than those with other histology. Sensitivity analyses showed that the total Edmonton Symptom Assessment System-Revised score was more improved in the OR group versus the SD group (median: 5 vs. 3, respectively; P = 0.029) and in the 'good-OR' group versus the 'moderate-OR and SD' group (median: 7.5 vs. 2, respectively; P = 0.003), suggesting that greater tumor shrinkage led to more symptom amelioration. CONCLUSIONS: Tumor shrinkage was associated with Edmonton Symptom Assessment System-Revised score improvement in patients with lung cancer receiving systemic therapy.

A practical method for determining film thickness using X-ray absorption spectroscopy in total electron yield mode.

Thin films formed on surfaces have a large impact on the properties of materials and devices. In this study, a method is proposed using X-ray absorption spectroscopy to derive the film thickness of a thin film formed on a substrate using the spectral separation and logarithmic equation, which is a modified version of the formula used in electron spectroscopy. In the equation, the decay length in X-ray absorption spectroscopy is longer than in electron spectroscopy due to a cascade of inelastic scattering of electrons generated in a solid. The modification factor, representing a multiple of the decay length, was experimentally determined using oxidized Si and Cu with films of thickness 19 nm and 39 nm, respectively. The validity of the proposed method was verified, and the results indicated that the method can be used in the analysis of various materials with thin films.

Improving photosensitivity without changing thermal reactivity in photochromic diarylbenzenes based on accurate prediction by DFT calculations.

1,2-Diarylbenzenes (DABs) have been developed as a new family of fast T-type photochromic switches. However, the molecular design strategy for DABs with desired optical and thermal properties is not established. In this work, we explored the best functional in quantum chemical calculations to predict the properties of DABs. Furthermore, we newly designed and synthesized DABs based on the calculation using the best functional, resulting in the improvement of the photosensitivity in the UV-A region (i.e. a shift of absorption to lower energies and an increase in the absorption coefficient) without changing the thermal back-reaction rate.

Sodium Vapor-Induced Synthesis of Intermetallic Pt5Ce Compound Nanoparticles.

We have developed a synthetic route that uses sodium for the production of intermetallic Pt5Ce nanoparticles (ca. 6 nm average diameter) supported on carbon powder. Sodium melt was demonstrated to reduce a powder mixture of PtCl2 and CeCl3 to form submicrometer Pt5Ce particles with the simultaneous formation of NaCl. The NaCl-CeCl3 melt mixture and Na melt were formed during heating, which led to a uniform reaction between Pt and Ce, and the melt induced grain growth. The synthetic procedures were then modified to supply sodium vapor to the vicinity of the metal sources supported on carbon powder with an aim to suppress grain growth. Pt5Ce nanoparticles were successfully formed on the carbon support with high loading and dispersity.

Thickness of carbon coatings on silicon materials determined by hard X-ray photoelectron spectroscopy at multiple photon energies.

Hard X-ray photoelectron spectroscopy at multiple photon energies is used to investigate the surface structure of carbon coatings on silicon materials destined for use as negative electrodes in lithium-ion batteries. The photoelectron intensity from the carbon coatings decreases with an increase in the kinetic energy of the photoelectron. By fitting the photoelectron intensity versus energy to numerically derived curves, the thickness and coverage of the carbon coatings can be obtained. The results are in agreement with the values suggested by the cross-sectional secondary-electron microscopy images of the carbon coatings, although the thickness should be corrected by accounting for the rectangular parallelepiped structure of the silicon material.

Local atomic structure analysis of GaN surfaces via X-ray absorption spectroscopy by detecting Auger electrons with low energies.

GaN is a promising material for power semiconductor devices used in next-generation vehicles. Its electrical properties such as carrier mobility and threshold voltage are affected by the interface between the oxide and the semiconductor, and identifying the interface states is important to improve these properties. A surface-sensitive measurement of Ga K-edge extended X-ray absorption fine structure (EXAFS) by detecting Ga LMM Auger electrons that originate from Ga K-shell absorption is proposed for GaN. LMM Auger electrons with low energies were detected and the EXAFS oscillation was confirmed, providing information on the Ga atoms at the surface. Investigation of thermally oxidized GaN with an oxide film of defined thickness showed that the analysis depth was less than 10 nm, which is consistent with the inelastic mean free path of 2.3 nm estimated for LMM Auger electrons in GaN.

Na-Melt Synthesis of Fine Ni3Si Powders as a Hydrogenation Catalyst.

Fine Ni3Si powders with high phase purity were successfully produced using a Na melt. The particle surface was less oxidized than that of metallurgically prepared Ni3Si. The Ni3Si catalyst exhibited much higher activities than Ni for the hydrogenation of various unsaturated hydrocarbons.

Effectiveness of Communication Studies Program at Tokyo Dental College Based on Comments from Members of Public in Educational Organization.

The purpose of this study was to investigate the effectiveness of the Communication Studies Program at Tokyo Dental College as a tool in behavioral education. The number of Patient Community members who had participated in multiple sets of the program for third-year students in the same year within the 3-year period spanning 2016 to 2018 (152, 148, and 129 students in 2016, 2017, and 2018 respectively), and the period during which they had participated in multiple sets were investigated. Comments on student behavior, including on hairstyle, clothes, and attitude, were also analyzed. The total number of members who had participated in multiple sets (1 set comprised 1 lecture and 2 training sessions) was 5; and their comments were more favorable during the second (sets 3 and 4) than the first half of the 1-month program (sets 1 and 2). During the first half, the students were criticized for speaking softly, having bad posture, not concentrating, and having an attitude inappropriate for a medical worker; but in the second half, they were praised for beginning to adopt the proper attitude for a medical worker, speaking louder, having better posture, and a very serious attitude. These findings suggest that the Communication Studies Program is effective in improving student behavior.

Band bending and dipole effect at interface of metal-nanoparticles and TiO2 directly observed by angular-resolved hard X-ray photoemission spectroscopy.

This paper describes the observation of band bending and band edge shifts at the interfaces between nanoscale metals and TiO2 film over a wide depth range by angular-resolved hard X-ray photoemission spectroscopy (HAXPES). The HAXPES results indicate strong electrostatic interactions between the TiO2 semiconductor and metal nanoparticles, while density functional theory (DFT) calculations suggest that these interactions are primarily associated with charge transfer leading to electric dipole moments at the interface in the ground state. The effects of these dipole moments are not limited to the surface but also occur deep in the bulk of the semiconductor, and are highly dependent on the coverage of the metal nanoparticles on the semiconductor species.

Activities and Stabilities of Au-Modified Stepped-Pt Single-Crystal Electrodes as Model Cathode Catalysts in Polymer Electrolyte Fuel Cells.

The purpose of this study is to test the concept of protecting vulnerable sites on cathode catalysts in polymer electrolyte fuel cells. Pt single-crystal surfaces were modified by depositing Au atoms selectively on (100) step sites and their electrocatalytic activities for oxygen reduction reaction (ORR) and stabilities against potential cycles were examined. The ORR activities were raised by 70% by the Au modifications, and this rise in the activity was ascribed to enhanced local ORR activities on Pt(111) terraces by the surface Au atoms. The Au modifications also stabilized the Pt surfaces against potential cycles by protecting the low-coordinated (100) step sites from surface reorganizations. Thus, the surface modification by selective Au depositions on vulnerable sites is a promising method to enhance both the ORR activity and durability of the catalysts.

Use of olanzapine for the relief of nausea and vomiting in patients with advanced cancer: a multicenter survey in Japan.

Nausea and vomiting are among the most common and distressing symptoms in patients with advanced cancer. Olanzapine, an antipsychotic agent, is known to have an affinity for multiple neurotransmitter receptors. Previous studies have reported olanzapine to be efficacious in the treatment of nausea and vomiting. Although it has been administered at a number of facilities, its applicability to treat nausea and vomiting in patients with advanced cancer is poorly understood. We investigated the use of olanzapine for nausea and vomiting in patients with advanced cancer at multiple centers. This retrospective study was carried out at seven palliative care units and three facilities with palliative care teams in Japan from 2013 to 2015. The dosage of olanzapine, treatment duration, and duration from initial use until death were collected from the medical records. One hundred and eight patients met our inclusion criteria. The average dose of olanzapine was 3.6 mg (2.5 mg, n = 61; 5 mg, n = 46; 10 mg, n = 1) and average treatment duration was 18.7 days. The average duration from initial use until death was 39.0 days. There were no differences in the duration of administration until death between olanzapine doses (2.5 and 5 mg). Our results suggest that olanzapine have been used in patients with poor prognoses for nausea and vomiting in patients with advanced cancer. Conducting a prospective trial would further yield promising results.

Participation of Patient Community Members in Communication Classes for Dental Students at Tokyo Dental College.

In 2009, the Ministry of Education, Culture, Sports, Science and Technology launched its "Program for Promoting University Education and Student Support, Theme A: Program for Promoting University Education Reform". The ministry's stated aims were to 1) enhance student training centered on the needs of the individual patient; 2) improve their ability to make comprehensive diagnosis and treatment plans; and 3) instill high ethical standards and good communication skills. One of the main pillars of this project was to establish an educational organization aimed at encouraging public participation, the "Patient Community". The aim was to have members of this community roleplay patients in the Communication Studies component of the 1st-4th years of dental school. It was hoped that they would be able to respond to the students in a more realistic manner than simulated patients. Here, the number of Patient Community members and number who attended Communication Studies classes in 2010, 2011, 2012, and 2014 were investigated. The results showed that the number registered in the Patient Community increased annually, as did the number participating in Communication Studies classes, which rose in accordance with the number of classes held. No difference was observed in the number of attendees per Communication Studies class by grade (years 1-4). The number of members never attending Community Studies classes increased annually, although some members repeatedly attended. These findings suggest that the members who regularly participate tend to remain the same.

Relationship between Obstructive Sleep Apnea and Self-assessed Oral Health Status: An Internet Survey.

The purpose of this study based on a cross-sectional internet survey was to investigate the relationship between risk of obstructive sleep apnea (OSA) and self-assessed oral health status. The participants, who comprised individuals registered with an online research company, were required to complete a self-reported questionnaire. Those answering in the affirmative to both of the following two questions were placed in the OSA-risk group, while those answering in the negative were assigned to the control group: 'Have other people noticed pauses in your breathing while you are sleeping?' and 'Do you feel excessively sleepy during the daytime?'. A total of 493 were included in the OSA-risk group and 2,560 in the control group. Among the total 3,053 respondents, the highest prevalence for OSA risk in men was in the 50-59-year age range, although this tended to level off after age 60 years. No such trend was observed in women, however. Multiple logistic regression analysis was performed to identify the relationship between risk of OSA and self-assessed oral health status. Significant correlations were observed with the following parameters: difficulty in opening mouth (odds ratio [OR]: 2.66; 95% confidence interval [CI]: 1.647-4.311), dry mouth (OR: 2.11; CI: 1.544-2.876), bad breath (OR: 1.69; CI: 1.309-2.186), gingival bleeding (OR: 1.48; CI: 1.134-1.932), and gingival swelling (OR: 1.44; CI: 1.046-1.981). These results suggest a relationship between risk of OSA and self-assessed oral health status, indicating that treating OSA might improve oral health status. Further study is needed to demonstrate a causal relationship between OSA and self-assessed oral health status, however.

Developmental morphology of the typical cordate gametophyte of a homosporous leptosporangiate fern, Lygodium japonicum (Lygodiaceae), focusing on the initial cell behavior of two distinct meristems.

PREMISE OF THE STUDY: Understanding the origin and early evolution of vascular plants requires thorough consideration of the gametophyte generation of ferns and lycophytes. Unfortunately, information about this generation is quite limited. To reveal the origin and evolution of varied gametophyte shapes, we used comparative morphological studies of meristem behavior of gametophytes of Lygodium japonicum, which exhibit the typical cordate shape. METHODS: Microscopic images of epi-illuminated growing gametophytes cultured from spores were captured periodically using a metallurgical microscope equipped with a digital camera to analyze the cell lineage in the meristem. KEY RESULTS: Gametophytes form from two meristems: the apical-cell-based meristem and the multicellular meristem. The triangular apical cell produces six to eight derivatives from two lateral facets, then disappears. Subsequently, the multicellular meristem, with a row of several rectangular cells, forms in the notch. These rectangular cells divide asynchronously in the periclinal and anticlinal walls to produce cells to both lateral sides and downward. Usually two, and sometimes three, cells located at the center of the meristem divide at a slower pace in the periclinal and anticlinal planes than others at the periphery. The cells at the periphery are pushed away and become involved in the wing base. CONCLUSIONS: The triangular apical cell behaves as a permanent initial cell. In the multicellular meristem, however, two or three central cells behave as initial cells that are transient and regulated in a position-dependent manner. The organization and behavior of both meristems are shared with the ribbon-shaped gametophytes of Colysis.

[LEIOMYOSARCOMA ARISING FROM OVARIAN VEIN WITH RIGHT HYDRONEPHROSIS: A CASE REPORT].

The patient was a 37-year-old woman who had suffered from repeated pyelonephritis. Computed tomography (CT) of the abdomen revealed a 1.9 cm retroperitoneal mass with compression of the right ureter and hydronephrosis. The patient visited our medical center and admitted. The patient underwent a simple total excision of the mass and end-to-end ureteral anastomosis. The tumor involved right ovarian vein and right ureter. Histopathological diagnosis was leiomyosarcoma of the ovarian vein. At 12 months after operation, local recurrence of surroundings tissue of the right ureter and gallbladder, and inferior vena cava invasion is found. Thus, the patient underwent a right nephroureterectomy with partly resection of the inferior vena cava and en block excision of the gallbladder. While CT revealed no recurrence three months after the operation, adjuvant postoperative combination chemotherapy with gemcitabine and docetaxel was administered. Nine cases of this leiomyosarcoma arising from ovarian vein have been reported in the literature. Leiomyosarcoma arising from ovarian vein with hydronephrosis is a second example.

Strong expression of cyclin B2 mRNA correlates with a poor prognosis in patients with non-small cell lung cancer.

Cyclin family proteins act in association with cyclin-dependent kinases (CDK) at cell cycle checkpoints to regulate the eukaryotic cell cycle. CyclinB2 contributes to G2/M transition by activating CDK1 kinase, and cyclin B2 inhibition induces cell cycle arrest. CyclinB2 is overexpressed in various human tumors, though the relationship between cyclin B2 expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood. In the present study, therefore, we investigated the relationship between cyclin B2 mRNA expression and the prognosis of patients with non-small cell lung cancer (NSCLC). We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of cyclin B2 mRNA in tumor samples from 79 patients with NSCLC. We then correlated the cyclin B2 mRNA levels with clinicopathological factors. We also used immunohistochemical staining to determine the localization of expressed cyclin B2. The 5-year overall survival rates among patients with adenocarcinoma of lung expressing lower levels of cyclin B2 mRNA were significantly better than the corresponding rates among patients expressing higher levels (p = 0.004). Multivariate Cox proportional hazard analyses revealed that gender ((hazard ratio (HR), 9.81; p = 0.044)), n2 (HR, 146.26; p ≤ 0.001), and cyclin B2 mRNA high (HR, 7.21; p = 0.021) were independent factors affecting the 5-year overall survival rates. However, there was no significance in the 5-year overall survival rates among the patients with squamous cell carcinoma between expressing lower and higher level of cyclin B2 mRNA. Stronger expression of cyclin B2 mRNA in tumor cells is an independent predictor of a poor prognosis in patients with adenocarcinoma of lung.

Inhibition of Hsp90 and 70 sensitizes melanoma cells to hyperthermia using ferromagnetic particles with a low Curie temperature.

BACKGROUND: Heat shock protein (Hsp) 90 is a key regulator of various oncogene products and cell-signaling molecules, while Hsp70 protects against heat-induced apoptosis. We previously described a system in which hyperthermia was produced using thermosensitive ferromagnetic particles (FMPs) with a Curie temperature (T c) of 43 °C to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, the antitumor effects of combining Hsp90 inhibitor (17DMAG) and Hsp70 inhibitor (quercetin) with FMP-mediated hyperthermia were examined. METHODS: Expressions of Hsp90/70 and Akt were evaluated using Western blotting in vitro. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMPs were then injected into the resultant tumors, and the mice were divided into groups treated with quercetin and/or 17DMAG with/without hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMPs increased and stabilized at the T c. The TUNEL method was used to determine whether hyperthermia induced apoptosis within tumors. RESULTS: In the group pretreated with hyperthermia + quercetin + 17DMAG, Akt expression was reduced in vitro, the incidence of apoptosis within tumors was greater, and tumor growth was significantly suppressed 20 days after FMP injection in vivo, compared with other treatment groups. The survival rates among tumor-bearing mice observed for a period of 40 days were significantly higher in the hyperthermia + quercetin + 17DMAG group. CONCLUSION: Combining Hsp90/70 inhibition with hyperthermia appears to increase their antitumor effects. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90/70 inhibition has important implications for cancer treatment.