Neuromelanin or DaT-SPECT: which is the better marker for discriminating advanced Parkinson's disease?

BACKGROUND AND PURPOSE: Whether the neuromelanin-positive substantia nigra pars compacta area (NM-SNc) on neuromelanin magnetic resonance imaging (NM-MRI) and the specific binding ratio (SBR) on 123 I-N-v-fluoropropyl-2b-carbomethoxy3b-(4-iodophenyl)nortropane single photon emission computed tomography (DaT-SPECT) can be correlated with motor fluctuations (MFs) in advanced Parkinson's disease (PD) was investigated. METHODS: Thirty-five PD patients (60 ± 13 years) and 23 healthy individuals as controls (59 ± 19 years) were enrolled. The relationships between NM-MRI and DaT-SPECT were prospectively examined in two subgroups divided according to the presence or absence of MFs. Multivariate analysis was performed using the Cox proportional hazard model to screen for association factors. RESULTS: The NM-SNc size was correlated with the SBR (Spearman's ρ = 0.43, P < 0.05). The NM-SNc size was significantly reduced in PD with MFs compared with the subgroup without (P < 0.001), whereas the SBR did not significantly differ between the groups. NM-SNc size was a significant association factor for MFs (hazard ratio 0.94, P = 0.04). In receiver operating characteristic analysis of the factors for MF occurrence, the area under the receiver operating characteristic curve of the NM-SNc size showed a significant difference of 0.89 (P < 0.05) but no significant difference was found in the SBR. CONCLUSIONS: NM-SNc size was significantly correlated with the SBR in PD, but several factors in advanced PD were more closely associated with NM-SNc size than the SBR. NM-MRI might reflect the status of advanced PD more accurately than DaT-SPECT. Therefore, NM-MRI appears to provide a better marker for discriminating advanced PD than DaT-SPECT.

Collective bulk carrier delocalization driven by electrostatic surface charge accumulation.

In the classic transistor, the number of electric charge carriers--and thus the electrical conductivity--is precisely controlled by external voltage, providing electrical switching capability. This simple but powerful feature is essential for information processing technology, and also provides a platform for fundamental physics research. As the number of charges essentially determines the electronic phase of a condensed-matter system, transistor operation enables reversible and isothermal changes in the system's state, as successfully demonstrated in electric-field-induced ferromagnetism and superconductivity. However, this effect of the electric field is limited to a channel thickness of nanometres or less, owing to the presence of Thomas-Fermi screening. Here we show that this conventional picture does not apply to a class of materials characterized by inherent collective interactions between electrons and the crystal lattice. We prepared metal-insulator-semiconductor field-effect transistors based on vanadium dioxide--a strongly correlated material with a thermally driven, first-order metal-insulator transition well above room temperature--and found that electrostatic charging at a surface drives all the previously localized charge carriers in the bulk material into motion, leading to the emergence of a three-dimensional metallic ground state. This non-local switching of the electronic state is achieved by applying a voltage of only about one volt. In a voltage-sweep measurement, the first-order nature of the metal-insulator transition provides a non-volatile memory effect, which is operable at room temperature. Our results demonstrate a conceptually new field-effect device, extending the concept of electric-field control to macroscopic phase control.

Multilayer coated grazing incidence condenser for large numerical aperture objective at wavelength of 4.5 nm.

A grazing incidence condenser is developed for objectives with large numerical aperture working in Carbon-window wavelength region (λ=4.4-5.0 nm) with the use of a point light source. The condenser is composed of four pieces of toroidal mirrors and a piece of the mirror was fabricated to evaluate the performance of the mirror. The radii of the toroidal mirror are determined by ray-trace calculation, and each radius of the mirror substrate and the roughness of the polished surface were evaluated to satisfy the designed parameter. A Co/C reflection multilayer is also designed to reflect soft x-ray light at 4.5 nm wavelength, and the reflection multilayer was deposited on the mirror surface. Measured reflectance of the toroidal mirror with the reflection multilayer is higher than 0.32 at 4.5 nm wavelength.

Design of soft x-ray varied-line-spacing (VLS) high-dispersion laminar-type grating coated with super-mirror-type (SMT) multilayer for flat-field spectrograph in a region of 2-4 keV.

A soft x-ray varied-line-spacing (VLS) laminar-type spherical grating with a super-mirror-type (SMT) multilayer was designed for a soft x-ray high resolution flat-field spectrograph in a region of 2-4 keV. The effective groove density of the designed VLS grating is 3200 lines/mm, and the local groove density varies from 2700 to 3866 lines/mm. The geometrical imaging property was evaluated by numerical calculations. The resolving power estimated by means of ray tracing was up to ∼103. For the evaluation of diffraction efficiency, the SMT multilayer structure designed for 3200 lines/mm in our previous work, Koike et al., Rev. Sci. Instrum. 94, 045109 (2023), was employed, and the numerical calculation was performed considering the local groove density of VLS grooves and the local incidence angle being affected by the curvature of the spherical surface and the geometrical relation between the source and incidence point on the grating. The results showed that the SMT multilayer-coated grating exhibited about an order of magnitude higher diffraction efficiency compared with an Au-coated grating.

Soft x-ray high diffraction efficiency and spectral flux laminar-type W/B4C multilayer diffraction grating for 300-1000 eV.

Multilayer diffraction gratings are designed to improve the detection limit and sensitivity of soft x-ray flat-field spectrographs in the region of 300-1000 eV, placing emphasis on Fe-L (705 eV), Cu-L (930 eV), and Zn-L (1012 eV) emissions. For this purpose, spectral flux was used as the performance index, which is proportional to the amount of optical flux incident into a detector and correlated with detection sensitivity. A super-mirror-type W/B4C multilayer coating [Koike et al., Rev.Sci. Instrum. 94, 045109 (2023)] was employed to improve diffraction efficiency in a wide energy region. The unique feature of the multilayer structure is that the average refractive index and the period length of W/B4C layer pairs are increased from the bottom to top layers. In addition, the incidence angle was reduced to 86.03° from 88.65° and the nominal groove density was increased to 3200 lines/mm from 2400 lines/mm of our previous design, to improve spectral flux while maintaining dispersion and spectral resolution. A holographic varied-line-spacing spherical grating and a soft x-ray flat-field spectrograph were designed, using the aspherical-wavefront-recording method, assuming the nominal grating constant and incident angle described above. The numerical simulation results showed that the spectrograph employing the newly designed grating with the W/B4C multilayer indicated 3.2-8.2 times higher spectral flux compared with those using the previously designed grating while keeping the same spectral resolution.

Sex and the clinical value of body mass index in patients with clear cell renal cell carcinoma.

BACKGROUND: An increased body mass index (BMI) is significantly associated with favourable prognosis in renal cell carcinoma (RCC). This study investigated the associations among sex, BMI, and prognosis in clear cell RCC patients. METHODS: We retrospectively analysed 435 patients with clear cell RCC who underwent a nephrectomy. The associations among sex, BMI, clinicopathologic factors, and cancer-specific survival (CSS) were analysed. RESULTS: As a continuous variable, increased BMI was associated with higher CSS rate by univariate analysis in the whole population (hazard ratio, 0.888 per kg m(-2); 95% confidence interval, 0.803-0.982; P=0.021). A sub-population analysis by sex demonstrated that BMI was significantly associated with CSS in men (P=0.004) but not in women (P=0.725). Multivariate analysis revealed BMI to be an independent predictor of CSS in only men. CONCLUSION: Body mass index was significantly associated with clear cell RCC prognosis. However, the clinical value of BMI may be different between men and women.

Two- and three-electron Pauli spin blockade in series-coupled triple quantum dots.

We investigate two- and three-electron spin blockade in three vertical quantum dots (QDs) coupled in series. Two-electron spin blockade is found in a region where sequential tunneling through all QDs is forbidden but tunneling involving virtual hopping through an empty QD is allowed. It is observed only for the hole cycle with a distinct bias threshold for access to the triplet state. Three-electron spin blockade involving the quadruplet state is observed for nonequibilium conditions where sequential tunneling is allowed and the triplet state is accessible. Our results shine light on the importance of the nonequibilium conditions to obtain sufficient population of triplet and quadruplet states necessary for spin blockade.

Design of soft x-ray laminar-type gratings coated with supermirror-type multilayer to enhance diffraction efficiency in a region of 2-4 keV.

Soft x-ray diffraction gratings coated with a supermirror-type multilayer were designed to enhance diffraction efficiency in the energy range of 2-4 keV by means of numerical calculations. The optimized groove depth and incidence angle are 2.05 nm and 88.65°, respectively, for the grating having a groove density of 3200 grooves/mm. Regarding the multilayer structure, the optimum number of B4C/W layers pair was 11 and the thickness of B4C was increased from bottom to top, while that of W was kept constant. The replacement of the top layer of W by either Co, Cr, or Ni was an effective means of obtaining uniform diffraction efficiency. In the region of 2-4 keV, the calculated diffraction efficiency of the designed gratings was up to ∼5.3%, on average, and almost eight times larger than that of ∼0.7% of an Au coated grating.

Laminar-type gratings overcoated with carbon-based materials to enhance analytical sensitivity of flat-field emission spectrograph in the VUV region.

Laminar-type spherical diffraction gratings overcoated with carbon-based materials were designed, fabricated, and evaluated for the purpose of enhancing the analytical sensitivity of the flat-field spectrograph in a vacuum ultraviolet region of 35-110 eV. As the design benchmark for numerical calculations, diffraction efficiency (DE) and spectral flux, which are defined by the product of the DE and numerical aperture and correlate with the analytical sensitivity of the spectrograph, were used. To simplify the feasibility study on the overcoating effects, we assumed a laminar-type grating having a grating constant of 1/1000 mm and coated with a Au layer of 30.0 nm thickness and an incidence angle of 84.0°. The optimized groove depth and duty ratio were 30.0 nm and 0.3, respectively. In addition, the optimum thicknesses of the overcoating layer were 44, 46, 24, and 30 nm for B4C, C, diamond-like-carbon, and SiC, respectively. Based on these results, we have fabricated a varied-line-spacing holographic grating overcoated with B4C with a thickness of 47 nm. For the experimental evaluation, we used the light source of Mg-L and Al-L emissions excited by the electron beam generated from an electron microscope, an objective flat-field spectrograph, and a CCD imaging detector. The experimental results showed that the spectrograph employing a new grating overcoated with the B4C layer indicated almost the same spectral resolution and 2.9-4.2 times higher analytical sensitivity compared with those obtained with a previously designed Au-coated grating having a grating constant of 1/1200 mm and used at an incidence of 86.0°.

ADC Level is Related to DWI Reversal in Patients Undergoing Mechanical Thrombectomy: A Retrospective Cohort Study.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, DWI lesions can occasionally be reversed by reperfusion therapy. This study aimed to ascertain the relationship between ADC levels and DWI reversal in patients with acute ischemic stroke who underwent recanalization treatment. MATERIALS AND METHODS: We conducted a retrospective cohort study in patients with acute ischemic stroke who underwent endovascular mechanical thrombectomy with successful recanalization between April 2017 and March 2021. DWI reversal was assessed through follow-up MR imaging approximately 24 hours after treatment. RESULTS: In total, 118 patients were included. DWI reversal was confirmed in 42 patients. The ADC level in patients with reversal was significantly higher than that in patients without reversal. Eighty-three percent of patients with DWI reversal areas had mean ADC levels of ≥520 × 10-6 mm2/s, and 71% of patients without DWI reversal areas had mean ADC levels of <520 × 10-6 mm2/s. The mean ADC threshold was 520 × 10-6 mm2/s with a sensitivity and specificity of 71% and 83%, respectively. In multivariate analysis, the mean ADC level (OR, 1.023; 95% CI, 1.013-1.033; P < .0001) was independently associated with DWI reversal. Patients with DWI reversal areas had earlier neurologic improvement (NIHSS at 7 days) than patients without reversal areas (P < .0001). CONCLUSIONS: In acute ischemic stroke, the ADC value is independently associated with DWI reversal. Lesions with a mean ADC of ≥520 × 10-6 mm2/s are salvageable by mechanical thrombectomy, and DWI reversal areas regain neurologic function. The ADC value is easily assessed and is a useful tool to predict viable lesions.

Aharonov-Bohm oscillations changed by indirect interdot tunneling via electrodes in parallel-coupled vertical double quantum dots.

Aharonov-Bohm (AB) oscillations are studied for a parallel-coupled vertical double quantum dot with a common source and drain electrode. We observe AB oscillations of current via a one-electron bonding state as the ground state and an antibonding state as the excited state. As the center gate voltage becomes more negative, the oscillation period is clearly halved for both the bonding and antibonding states, and the phase changes by half a period for the antibonding state. This result can be explained by a calculation that takes account of the indirect interdot coupling via the two electrodes.

Coherent terahertz emission of intrinsic Josephson junction stacks in the hot spot regime [corrected].

We report on THz emission measurements and low temperature scanning laser imaging of Bi2Sr2CaCu2O8 intrinsic Josephson junction stacks. Coherent emission is observed at large dc input power, where a hot spot and a standing wave, formed in the "cold" part of the stack, coexist. By changing bias current and bath temperature, the emission frequency can be varied by more than 40%; the variation matches the Josephson-frequency variation with voltage. The linewidth of radiation is much smaller than expected from a purely cavity-induced synchronization. Thus, an additional mechanism seems to play a role. Some scenarios, related to the presence of the hot spot, are discussed.

Thin film growth of CaAgAs by molecular beam epitaxy.

We have grown thin films of CaAgAs by molecular beam epitaxy, which was theoretically proposed to be a topological insulator. The temperature dependence of resistivity and the carrier concentration at 4 K were similar to the reported results of bulk samples. However, the magnetoresistance exhibited a steep increase at low magnetic fields, a behavior not observed for bulk samples. This steep increase of resistivity is ascribable to the weak antilocalization effect and provides clues to the nature of the topological surface state of CaAgAs.

Unmet needs of patients with Parkinson's disease: interview survey of patients and caregivers.

We performed a 20-item questionnaire-based interview of 132 patients with Parkinson's disease (PD): 81 patients with Hoehn & Yahr (H&Y) stage I - III PD, and 51 caregivers of patients with H&Y stage IV - V PD, to evaluate patient and caregiver satisfaction with PD treatment. The survey revealed that PD patients often experience non-motor symptoms, which are not adequately alleviated by antiparkinsonian agents. Furthermore, PD patients want their physicians to listen to them and take their concerns seriously, to explain their disease comprehensively, and to provide the latest information on PD and its treatment. Both patients and caregivers agreed on anxiety toward the future, communication difficulties, and their different movement pace; however, there were differences in their relative perceptions of various aspects of daily care. The evaluation revealed that PD patients have unmet needs in their treatment and standards of care. Areas for future improvement as highlighted in this study include: the development of better treatment for motor symptoms, the development of new treatments for non-motor symptoms and improved two-way communication between patient and physician.

Combined treatment using CEA and CAS for carotid arterial stenosis.

In this study we report our surgical results of CAS and CEA for carotid stenosis and suggest an appropriate treatment strategy for patients with high risks such as bilateral carotid stenosis or medical risk factors. From January 2001 to December 2005 we surgically treated 182 patients with carotid stenosis. Seventy-nine lesions were treated by CEA and 145 by CAS, respectively. Although CEA was considered the first choice for severe carotid stenosis, CAS was chosen for treatment when CEA was considered a higher risk for patients. Stenosis of carotid arteries was relieved in all cases after CEA or CAS. Surgical mortality of CEA was 1.1% (1/94). Surgical mortality of CAS was 0.7% (1/145). Carotid stenotic lesions can be treated with comparably low morbidity and mortality rates using CEA or/and CAS considering each characteristic of carotid stenosis of patients even with medically high risk or bilateral carotid stenosis.

Correction to: Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer.

[This corrects the article DOI: 10.1186/s40364-017-0099-2.].

Selective mass enhancement close to the quantum critical point in BaFe2(As1-x P x )2.

A quantum critical point (QCP) is currently being conjectured for the BaFe2(As1-x P x )2 system at the critical value x c ≈ 0.3. In the proximity of a QCP, all thermodynamic and transport properties are expected to scale with a single characteristic energy, given by the quantum fluctuations. Such a universal behavior has not, however, been found in the superconducting upper critical field H c2. Here we report H c2 data for epitaxial thin films extracted from the electrical resistance measured in very high magnetic fields up to 67 Tesla. Using a multi-band analysis we find that H c2 is sensitive to the QCP, implying a significant charge carrier effective mass enhancement at the doping-induced QCP that is essentially band-dependent. Our results point to two qualitatively different groups of electrons in BaFe2(As1-x P x )2. The first one (possibly associated to hot spots or whole Fermi sheets) has a strong mass enhancement at the QCP, and the second one is insensitive to the QCP. The observed duality could also be present in many other quantum critical systems.

Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma.

A bovine serum albumin-conjugated doxorubicin via the glutaraldehyde bridge (BSA-DXR conjugate) showed potent dose-dependent inhibition of cell growth against daunorubicin-resistant AH66 (AH66DR) cells as well as parental AH66 (AH66P) cells in vitro as compared to treatment with DXR or BSA-glutaraldehyde conjugate without DXR (BSA-GA). In the culture of AH66DR with BSA-DXR conjugate, drug accumulation in the AH66DR cells increased as a function of time up to 24 h reaching approximately the same drug level as AH66P cells treated with DXR. The intracellular accumulation of the BSA-DXR conjugate was inhibited by the addition of ammonium chloride, while that of DXR alone was not inhibited. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate or pharmacologically active DXR adduct remained in the cells at a relatively high concentration over a 36-h time period. The life-prolonging effect of the conjugate was assessed using rats inoculated i.p. with AH66P or AH66DR. The rats were treated with the BSA-DXR conjugate, DXR, a mixture of DXR with BSA, or BSA-GA by either the i.p. or i.v. route. Treatment with DXR had no significant surviving effect as compared to that with saline in AH66P-bearing rats. By contrast, BSA-DXR conjugate showed a significant life-prolonging effect as compared with DXR alone in the same degree both in AH66P- and AH66DR-bearing rats. BSA-GA did not show any toxicity in vivo as well as in vitro. These results indicate that the BSA-DXR conjugate allows DXR to escape from the multidrug resistance mechanism.

Establishment of a novel species- and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone.

Bone is the most common site of metastasis in prostate cancer (PC), and to generate an animal model to investigate the basis of the unique organ tropism of PC cells for bone, we engrafted humanized non-obese diabetic/severe combined immunodeficient (NOD/SCID-hu) mice with human adult bone (HAB) and lung (HAL). Human PC cell lines LNCaP (1 x 10(7)) and PC-3 (5 x 10(6)) were injected into male NOD/SCID-hu mice via the lateral tail vein at 3-4 weeks after implantation. At 8 weeks after the injection, LNCaP and PC-3 cells had metastasized specifically to HAB in 35 and 65%, respectively, of the mice. The tumors formed by LNCaP appeared to be the osteoblastic type, whereas the PC-3 tumors consisted of osteolytic lesions without any surrounding osteogenic response. A feature of experimental metastasis of PC in NOD/SCID-hu mice was its specificity for HAB tissue. Human PC cells had no or very low metastatic potential in regard to implanted HAL, mouse bone, or native mouse bone. These findings indicate that metastasis of PC cells to HAB is both species and tissue specific. The availability of this small animal model could provide a useful tool for identifying and analyzing important features of the human PC metastatic process that cannot be addressed in conventional metastasis models.