Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings (AU)

Fabrication of Hydrogen Boride Thin Film by Ion Exchange in MgB2.

In this study, hydrogen boride films are fabricated by ion-exchange treatment on magnesium diboride (MgB2) films under ambient temperature and pressure. We prepared oriented MgB2 films on strontium titanate (SrTiO3) substrates using pulsed laser deposition (PLD). Subsequently, these films were treated with ion exchangers in acetonitrile solution. TOF-SIMS analysis evidenced that hydrogen species were introduced into the MgB2 films by using two types of ion exchangers: proton exchange resin and formic acid. According to the HAXPES analysis, negatively charged boron species were preserved in the films after the ion-exchange treatment. In addition, the FT-IR analysis suggested that B-H bonds were formed in the MgB2 films following the ion-exchange treatment. The ion-exchange treatment using formic acid was more efficient compared to the resin treatment; with respect to the amount of hydrogen species introduced into the MgB2 films. These ion-exchanged films exhibited photoinduced hydrogen release as observed in a powder sample. Based on the present study, we expect to be able to control the morphology and hydrogen content of hydrogen boride thin films by optimising the ion-exchange treatment process, which will be useful for further studies and device applications.

Temperature dependence on bandgap of semiconductor photocatalysts.

Light irradiation onto a semiconductor generates heat; however, its electronic structure under high temperature has not yet been well investigated. In this study, we have carefully examined the temperature dependence on the bandgap of simple metal oxides, which are well-known photocatalysts, i.e., TiO2, CeO2, Nb2O5, SnO2 Ta2O5, WO3, ZnO, and ZrO2, using operando UV-visible spectroscopy under controlled temperature (from room temperature to 500 °C). Consequently, a linear decrease in bandgap was seen as a function of temperature with a different slope for each semiconductor. We found that the slope was dependent on the bonding distance between metal and oxygen. This finding is essential to develop a photocatalyst used under the condition involving photo-thermal effect.

Energy of the

The low-lying isomeric state of ^{229}Th provides unique opportunities for high-resolution laser spectroscopy of the atomic nucleus. We determine the energy of this isomeric state by taking the absolute energy difference between the excitation energy required to populate the 29.2-keV state from the ground state and the energy emitted in its decay to the isomeric excited state. A transition-edge sensor microcalorimeter was used to measure the absolute energy of the 29.2-keV γ ray. Together with the cross-band transition energy (29.2 keV→ground) and the branching ratio of the 29.2-keV state measured in a recent study, the isomer energy was determined to be 8.30±0.92 eV. Our result is in agreement with the latest measurements based on different experimental techniques, which further confirms that the isomeric state of ^{229}Th is in the laser-accessible vacuum ultraviolet range.

Narrow-line Cooling and Determination of the Magic Wavelength of Cd.

We experimentally and theoretically determine the magic wavelength of the (5s^{2})^{1}S_{0}-(5s5p)^{3}P_{0} clock transition of ^{111}Cd to be 419.88(14) and 420.1(7) nm. To perform Lamb-Dicke spectroscopy of the clock transition, we use narrow-line laser cooling on the ^{1}S_{0}-^{3}P_{1} transition to cool the atoms to 6 µK and load them into an optical lattice. Cadmium is an attractive candidate for optical lattice clocks because it has a small sensitivity to blackbody radiation and its efficient narrow-line cooling mitigates higher order light shifts. We calculate the blackbody shift, including the dynamic correction, to be fractionally 2.83(8)×10^{-16} at 300 K, an order of magnitude smaller than that of Sr and Yb. We also report calculations of the Cd ^{1}P_{1} lifetime and the ground state C_{6} coefficient.

Síndrome de Klinefelter y riesgo cardiovascular / Klinefelter syndrome and cardiovascular risk

Se presenta a un paciente de 45 años de edad que presenta síndrome de Klinefelter, con antecedentes de diabetes mellitus tipo 2, obesidad, dislipidemia, síndrome de apneas hipopneas del sueño e hipertensión arterial oculta. El objetivo de esta presentación es alertar sobre el riesgo cardiovascular aumentado que presentan estos pacientes y revisar los datos de la literatura que estudian dicho riesgo

We present a 45-year-old patient with Klinefelter syndrome, with a history of type 2 diabetes mellitus, obesity, dyslipidemia, obstructive sleep apnoea syndrome and masked arterial hypertension. The purpose of this presentation is to draw attention to the increased cardiovascular risk in these patients and to review the data in the literature on this risk

[Klinefelter syndrome and cardiovascular risk]. / Síndrome de Klinefelter y riesgo cardiovascular.

We present a 45-year-old patient with Klinefelter syndrome, with a history of type 2 diabetes mellitus, obesity, dyslipidemia, obstructive sleep apnoea syndrome and masked arterial hypertension. The purpose of this presentation is to draw attention to the increased cardiovascular risk in these patients and to review the data in the literature on this risk.

Fast x-ray detector system with simultaneous measurement of timing and energy for a single photon.

We developed a fast X-ray detector system for nuclear resonant scattering (NRS) experiments. Our system employs silicon avalanche photo-diode (Si-APD) as a fast X-ray sensor. The system is able to acquire both timing and energy of a single X-ray photon simultaneously in a high rate condition, 106 counts per second for one Si-APD. The performance of the system was investigated in SPring-8, a synchrotron radiation facility in Japan. Good time resolution of 120 ps (FWHM) was achieved with a slight tail distribution in the time spectrum by a level of 10-9 at 1 ns apart from the peak. Using this system, we successfully observed the NRS from the 26.27-keV level of mercury-201, which has a half-life of 630(50) ps. We also demonstrated the reduction of background events caused by radioactive decays in a radioactive sample by discriminating photon energy.

Development of C6⁺ laser ion source and RFQ linac for carbon ion radiotherapy.

A prototype C(6+) injector using a laser ion source has been developed for a compact synchrotron dedicated to carbon ion radiotherapy. The injector consists of a laser ion source and a 4-vane radio-frequency quadrupole (RFQ) linac. Ion beams are extracted from plasma and directly injected into the RFQ. A solenoid guides the low-energy beams into the RFQ. The RFQ is designed to accelerate high-intensity pulsed beams. A structure of monolithic vanes and cavities is adopted to reduce its power consumption. In beam acceleration tests, a solenoidal magnetic field set between the laser ion source and the RFQ helped increase both the peak currents before and after the RFQ by a factor of 4.

Spin-dependent acoustic response in the nonunitary A1 and A2 phases of superfluid 3He under high magnetic fields.

The transverse acoustic impedance of superfluid ^{3}He was measured in the A1 and A2 phases up to 13 T to investigate the surface states in nonunitary superfluids. The temperature dependence of the impedance was much larger in the A1 phase than in the A2 phase. This nonsymmetric behavior indicates that momentum exchange with walls for spin-down surface states is quite different from that for spin-up surface states. The spin-dependent response might be a reflection of an essential feature of the nonunitary states where gap amplitudes depend on spin states. Weak-coupling theories ignore any spin-dependent processes and do not account for the nonsymmetric behavior.

Tooth loss and atherosclerosis: the Nagahama Study.

Several epidemiologic studies have suggested that oral disease is a risk factor for cardiovascular disease (CVD). However, whether a clinically significant association exists between the 2 disorders remains controversial. Here, we investigated the association between tooth loss, as an indicator of oral disease, and arterial stiffness, as a marker of atherosclerosis, in Japanese adults. Cross-sectional data were collected for 8,124 persons aged 30 to 75 y with no history of tooth loss for noninflammatory reasons, such as orthodontic treatment, malposition, and trauma. Participants received a comprehensive dental examination and extensive in-person measurements of CVD risk factors, and arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). We examined the association between CAVI and tooth loss using general linear models with adjustment for age, sex, body mass index, smoking status, hemoglobin A1c, and a history of insulin or hypoglycemic medication depending on the model. In addition, we performed an analysis that included interaction terms of the centered variables tooth loss, sex, and age. The results of the multiple regression analysis that included the interaction terms detected that the relationship between CAVI and tooth loss was dependent on sex, with only men showing a positive correlation (ß for interaction = 0.04; 95% confidence interval, 0.02-0.06). The findings from this study suggest that a linear relationship exists between tooth loss and degree of arterial stiffness and that the association differed depending on sex.

From serendipitous assembly to controlled synthesis of 3d-4f single-molecule magnets.

Learning from serendipitous assembly, we have prepared a new family of designed 3d-4f Mn6Ln complexes. The dynamics of relaxation of the magnetization via alternating-current magnetic susceptibility for the new Mn6Ln complexes 1 (Ln = La), 2 (Ln = Tb), and 4 (Ln = Dy) have been studied down to 0.2 K.

Identification and characterization of PDGFRα+ mesenchymal progenitors in human skeletal muscle.

Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFRα as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFRα(+) cells represent a cell population distinct from CD56(+) myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFRα(+) population. Activation of PDGFRα stimulates proliferation of PDGFRα(+) cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFRα(+) cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFRα(+) mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.

Measurement of beam characteristics from C(6+) laser ion source.

We developed a C(6+) laser ion source for a heavy-ion accelerator. A carbon target was irradiated with a Q-switched Nd:YAG laser (1064 nm wavelength, 1.4 J maximum laser energy, 10 ns pulse duration) to generate a high-density plasma. The laser ion source employed a rotating carbon target for continuous operation. Ion beams were extracted from the plasma through a drift space using a direct plasma injection scheme [B. Yu. Sharkov, A. V. Shumshurov, V. P. Dubenkow, O. B. Shamaev, and A. A. Golubev, Rev. Sci. Instrum. 63, 2841 (1992)] up to a maximum voltage of 40 kV. We measured the characteristics of the ion beams from the laser ion source and present the results of experiments here.

Clinical characteristics classified by the serum KL-6 level in patients with organizing pneumonia.

BACKGROUND: The serum Krebs von der Lungen-6 (KL-6) level is a useful marker correlated with the severity of various interstitial lung diseases. There have been few reports about the clinical characteristics of organizing pneumonia (OP) associated with the serum KL-6 levels. OBJECTIVE: This study was performed to determine whether the serum KL-6 levels can help determine the optimal treatment for OP. DESIGNS: Patients diagnosed with OP by clinical, radiological and histopathological findings were retrospectively reviewed. The OP patients were classified into two groups based on their serum KL-6 levels: normal KL-6 and high KL-6 groups. The two groups were compared with regard to their clinical and radiological data and therapeutic response one month after the start of treatment. RESULTS: The clinical records of twenty-two patients diagnosed with OP were reviewed. The serum KL-6 level was elevated in 11 of the 22 patients. There were no obvious differences in the clinical data between the two groups, although patients in the normal KL-6 group tended to have a fever. There were no significant differences in the chest X-ray (CXR) score or computed tomography (CT) score between the two groups. The CXR scores were correlated with the serum KL-6 levels. At 1 month after the diagnosis, 11 patients who needed treatment with prednisolone were included in the high KL-6 group. CONCLUSIONS: Patients with normal KL-6 levels showed lower CXR and CT scores. The serum KL-6 level on admission is a useful marker to judge the need for corticosteroid treatment in OP patients.

The role of osteocytes in bone resorption during orthodontic tooth movement.

We investigated the roles of osteocytes in osteoclastic bone resorption during orthodontic tooth movement using the transgenic mice in which osteocytes can be specifically ablated. Because these transgenic mice express the receptor for diphtheria toxin on the cell surfaces of osteocytes, the injection of diphtheria toxin can ablate their osteocytes in vivo. Injection of diphtheria toxin into the transgenic mice significantly increased the number of ablated osteocytes in alveolar bone compared with that in wild-type mice with or without diphtheria toxin injection. Increased numbers of ablated osteocytes were observed from day 4 to day 12 after the injection in alveolar bones as well as in cortical bone of the tibiae. We applied the orthodontic force 4 days after the injection of diphtheria toxin, and the distance of tooth movement on day 12 was significantly smaller in transgenic mice than that in control mice. The numbers of osteoclasts and the quantity of eroded bone surface at the compression site were significantly reduced in the transgenic mice injected with diphtheria toxin than in control mice. These results provide in vivo demonstration of osteocyte involvement in osteoclastic bone resorption during orthodontic tooth movement.

Visual perceptual strengths and weaknesses in adults with intellectual disabilities compared with a birth year-matched norm.

BACKGROUND: The ventral and dorsal streams are considered to be the brain substrates of vision for perception and action, respectively. Using the Developmental Test of Visual Perception (DTVP), the current study examined whether visual perceptual strengths and weaknesses in adults with intellectual disabilities (ID) were attributable to the dichotomy of the visual streams. METHOD: In study 1, DTVP performance was compared among mild, moderate and severe adult ID groups; study 2 contrasted adult ID groups with and without Down syndrome (DS). To prevent possible contamination by the Flynn effect, participants were matched by birth year with the norm of the DTVP original edition. RESULTS: Independent of the extent of ID among the three groups in study 1 and the aetiological group difference in study 2, relative strength was found for two DTVP tasks: eye-hand coordination and distinguishing target figures from interference background. Relative weakness was obtained in identifying a figural category. Participants with DS demonstrated exceptional weakness in discerning a target from either mirror-imaged or rotated alternatives, in addition to figural-category detection. CONCLUSIONS: Visual perceptual strengths and weaknesses in persons with ID were difficult to explain on the basis of two visual streams. An interpretation originating in a different research context (e.g. frontal-lobe dysfunction) appears to be required for explaining visual perceptual weaknesses in persons with ID. For persons with DS, strong frontal-lobe dysfunction with atypical lateralisation might be the pathological determinant of visual perceptual weaknesses.

New (99m)Tc(CO)(3) mannosylated dextran bearing S-derivatized cysteine chelator for sentinel lymph node detection.

The aim of the present study is to synthesize new mannosylated dextran derivative that can be labeled with Tc-99m for potential use in sentinel lymph node detection (SLND). The compound was designed to have a dextran with molecular weight of 10 kDa as a backbone, mannose for binding to mannose receptors of the lymph node and S-derivatized cysteine as a suitable chelator for labeling with [(99m)Tc(H(2)O)(3)(CO)(3)](+) precursor. Reaction of allyl bromide with dextran (MW 11800) yielded the intermediate allyl-dextran (1) with about 40% coupling. Addition of cysteine to allyl-dextran resulted in the S-derivatized cysteine, compound DC15 (2). The final product DCM20 (3) was obtained in good yield after in situ hydrolysis and activation of cyanomethyl tetraacetyl-1-thio-d-mannopyranoside and coupling to DC15. All derivatives were purified by ultrafiltration and characterized by NMR. DC15 and DCM20 were quantitatively labeled with (99m)Tc (>95% radiochemical purity) using the fac-[(99m)Tc(OH(2))(3)(CO)(3)](+) precursor and ligand concentration of 1.5 × 10(-6) M at neutral pH. Both (99m)Tc-labeled compounds (99m)Tc(CO)(3)-DC15 (6) and (99m)Tc(CO)(3)-DCM20 (7) remained stable after 6 h incubation at 37 °C in the presence of excess histidine or cysteine, as well as even after 20-fold dilution and incubation for 24 h at room temperature. The characterization of the compounds 6 and 7 was performed by comparing their HPLC radiochromatograms with those of their rhenium surrogates Re(CO)(3)-DC15 (4) and Re(CO)(3)-DCM20 (5) respectively that were prepared using the precursor [NEt(4)](2)fac-[ReBr(3)(CO)(3)] and characterized by IR and NMR spectroscopy. When injected subcutaneously from the foot pad of mice, (99m)Tc-labeled mannosylated dextran (7) showed accumulation in the popliteal lymph node (SLN in this model) higher than that of non-mannosylated analogue (6) and the (99m)Tc-phytate serving as standard. Compound 7 also exhibited lower radioactivity levels at the injection site compared to (99m)Tc-phytate. The SPECT/CT studies in mice confirmed that 7 accumulated in the popliteal lymph node allowing its clear visualization. The present findings demonstrate that compound 7 ((99m)Tc(CO)(3)-DCM20) is promising and merits further evaluation as a radiopharmaceutical for sentinel lymph node detection.