Validation of the REM behaviour disorder phenoconversion-related pattern in an independent cohort.

BACKGROUND: A brain glucose metabolism pattern related to phenoconversion in patients with idiopathic/isolated REM sleep behaviour disorder (iRBDconvRP) was recently identified. However, the validation of the iRBDconvRP in an external, independent group of iRBD patients is needed to verify the reproducibility of such pattern, so to increase its importance in clinical and research settings. The aim of this work was to validate the iRBDconvRP in an independent group of iRBD patients. METHODS: Forty iRBD patients (70 ± 5.59 years, 19 females) underwent brain [18F]FDG-PET in Seoul National University. Thirteen patients phenoconverted at follow-up (7 Parkinson disease, 5 Dementia with Lewy bodies, 1 Multiple system atrophy; follow-up time 35 ± 20.56 months) and 27 patients were still free from parkinsonism/dementia after 62 ± 29.49 months from baseline. We applied the previously identified iRBDconvRP to validate its phenoconversion prediction power. RESULTS: The iRBDconvRP significantly discriminated converters from non-converters iRBD patients (p = 0.016; Area under the Curve 0.74, Sensitivity 0.69, Specificity 0.78), and it significantly predicted phenoconversion (Hazard ratio 4.26, C.I.95%: 1.18-15.39). CONCLUSIONS: The iRBDconvRP confirmed its robustness in predicting phenoconversion in an independent group of iRBD patients, suggesting its potential role as a stratification biomarker for disease-modifying trials.

Investigating the relationship between the SNCA gene and cognitive abilities in idiopathic Parkinson's disease using machine learning.

Cognitive impairments are prevalent in Parkinson's disease (PD), but the underlying mechanisms of their development are unknown. In this study, we aimed to predict global cognition (GC) in PD with machine learning (ML) using structural neuroimaging, genetics and clinical and demographic characteristics. As a post-hoc analysis, we aimed to explore the connection between novel selected features and GC more precisely and to investigate whether this relationship is specific to GC or is driven by specific cognitive domains. 101 idiopathic PD patients had a cognitive assessment, structural MRI and blood draw. ML was performed on 102 input features including demographics, cortical thickness and subcortical measures, and several genetic variants (APOE, MAPT, SNCA, etc.). Using the combination of RRELIEFF and Support Vector Regression, 11 features were found to be predictive of GC including sex, rs894280, Edinburgh Handedness Inventory, UPDRS-III, education, five cortical thickness measures (R-parahippocampal, L-entorhinal, R-rostral anterior cingulate, L-middle temporal, and R-transverse temporal), and R-caudate volume. The rs894280 of SNCA gene was selected as the most novel finding of ML. Post-hoc analysis revealed a robust association between rs894280 and GC, attention, and visuospatial abilities. This variant indicates a potential role for the SNCA gene in cognitive impairments of idiopathic PD.

Fluorescence from Multiple Chromophore Hydrogen-Bonding States in the Far-Red Protein TagRFP675.

Far-red fluorescent proteins are critical for in vivo imaging applications, but the relative importance of structure versus dynamics in generating large Stokes-shifted emission is unclear. The unusually red-shifted emission of TagRFP675, a derivative of mKate, has been attributed to the multiple hydrogen bonds with the chromophore N-acylimine carbonyl. We characterized TagRFP675 and point mutants designed to perturb these hydrogen bonds with spectrally resolved transient grating and time-resolved fluorescence (TRF) spectroscopies supported by molecular dynamics simulations. TRF results for TagRFP675 and the mKate/M41Q variant show picosecond time scale red-shifts followed by nanosecond time blue-shifts. Global analysis of the TRF spectra reveals spectrally distinct emitting states that do not interconvert during the S1 lifetime. These dynamics originate from photoexcitation of a mixed ground-state population of acylimine hydrogen bond conformers. Strategically tuning the chromophore environment in TagRFP675 might stabilize the most red-shifted conformation and result in a variant with a larger Stokes shift.

Far-Red Emission of mPlum Fluorescent Protein Results from Excited-State Interconversion between Chromophore Hydrogen-Bonding States.

Fluorescent proteins with large Stokes shifted emission beyond 600 nm are actively sought for live-cell imaging applications. The mechanism of excited-state relaxation leading to the Stokes shift in the mPlum fluorescent protein, which emits at a peak wavelength of 650 nm, has been previously investigated by both ultrafast spectroscopy and theoretical methods. Here, we report that femtosecond time-resolved area-normalized emission spectra of mPlum show a clear isoemissive point. This feature can only result from a system with two emitting states, rather than a system that undergoes a continuous spectral red shift, for example, as expected from typical solvation. Global analysis of the femtosecond time-resolved fluorescence spectra reveals time constants associated with chromophore relaxation, excited-state population transfer, and an excited-state lifetime of the final state. The observations confirm the findings of recent quantum chemical calculations on mPlum.

Ultrafast generation of fundamental and multiple-order phonon excitations in highly enriched (6,5) single-wall carbon nanotubes.

Using a macroscopic ensemble of highly enriched (6,5) single-wall carbon nanotubes, combined with high signal-to-noise ratio and time-dependent differential transmission spectroscopy, we have generated vibrational modes in an ultrawide spectral range (10-3000 cm(-1)). A total of 14 modes were clearly resolved and identified, including fundamental modes of A, E1, and E2 symmetries and their combinational modes involving two and three phonons. Through comparison with continuous wave Raman spectra as well as calculations based on an extended tight-binding model, we were able to identify all the observed peaks and determine the frequencies of the individual and combined modes. We provide a full summary of phonon frequencies for (6,5) nanotubes that can serve as a basic reference with which to refine our understanding of nanotube phonon spectra as well as a testbed for new theoretical models.

Retrieval of frequency spectrum from time-resolved spectroscopic data: comparison of Fourier transform and linear prediction methods.

Femtosecond time-resolved signals often display oscillations arising from the nuclear and electronic wave packet motions. Fourier power spectrum is generally used to retrieve the frequency spectrum. We have shown by numerical simulations and coherent phonon spectrum of single walled carbon nanotubes (SWCNT) that the Fourier power spectrum may not be appropriate to obtain the spectrum, when the peaks overlap with varying phases. Linear prediction singular value decomposition (LPSVD) can be a good alternative for this case. We present a robust way to perform LPSVD analysis and demonstrate the method for the chirality assignment of SWCNT through the time-domain coherent phonon spectroscopy.

Photoswitchable quantum dots by controlling the photoinduced electron transfers.

We report photoluminescence (PL) modulation of quantum dots (QDs) by photoinduced electron transfers from acridine-1,8-dione derivative surface ligands. Reversible PL switching upon many repeated cycles was demonstrated, as alternating on and off of the UV excitation for the surface ligand has successfully resulted in the QD PL modulation.

Modest changes in cerebral glucose metabolism in patients with sleep apnea syndrome after continuous positive airway pressure treatment.

BACKGROUND: Decreased cerebral glucose metabolism has been reported in patients with sleep apnea syndrome (SAS), but it has yet to be decided whether cerebral glucose metabolism in SAS can be altered by continuous positive airway pressure (CPAP) treatment. OBJECTIVE: The aim of this study was to evaluate cerebral glucose metabolism changes in patients with SAS after CPAP treatment. METHODS: Thirteen middle-aged male patients with severe SAS [mean age 49.3 ± 7.2 years, mean apnea-hypopnea index (AHI) 60.4 ± 21.2] and 13 male controls (mean age 46.0 ± 9.4 years, mean AHI 4.1 ± 3.7) participated in the study. All 26 study subjects underwent fluorodeoxyglucose-positron emission tomography (FDG-PET), but SAS patients underwent FDG-PET twice, namely before and 3 months after acceptable CPAP usage. RESULTS: Significant hypometabolism was observed in the bilateral prefrontal areas, left cuneus and left cingulate cortex of SAS patients before CPAP, and after CPAP, significant increases in cortical glucose metabolism were observed in the bilateral precentral gyri and left anterior cingulate cortex. However, these improvements in hypometabolism in both areas were insufficient to reach control levels, and hypometabolism in other regions persisted after CPAP treatment. CONCLUSIONS: Reduced cerebral glucose metabolism in the precentral gyrus and the cingulate cortex in patients with SAS was modestly improved by acceptable CPAP treatment. The findings of this study suggest that acceptable CPAP usage cannot completely reverse reduced cerebral glucose metabolism in SAS patients. Further studies are required to evaluate the long-term effects of CPAP treatment with total compliance.

The use of an in vitro adenosine triphosphate-based chemotherapy response assay to predict chemotherapeutic response in breast cancer.

The adenosine triphosphate-based chemotherapy response assay (ATP-CRA) has the advantages of standardization, evaluability, reproducibility, and accuracy, and can be performed on relatively small numbers of tumor cells. A total of 43 patients were enrolled in the present study, and chemosensitivity tests were successfully performed in 40 (93.0%) of these patients. Twenty of the 40 received neoadjuvant chemotherapy or chemotherapy for metastatic breast cancer. The chemotherapy regimens used were doxorubicin plus docetaxel (n=9, 45.0%) or doxorubicin plus paclitaxel (n=11, 55.0%). Mean cell death rate, as determined by ATP-CRA, was lower in non-responders than in responders to therapy (P=0.012). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for ATP-CRA were 78.6%, 100%, 100%, 66.7%, and 85.0%, respectively. Diagnostic accuracy achieved by immunohistochemistry using estrogen receptor or progesterone receptor was lower than that achieved using ATP-CRA. Expression of p53, erb-B2, Ki67, Bcl-2, Bcl-xL, and annexin I was not significantly associated with response to chemotherapy. Our results show that ATP-CRA has high specificity and positive predictive value for predicting response to chemotherapy.

99mTc-labeled 1-thio-beta-D-glucose as a new tumor-seeking agent: synthesis and tumor cell uptake assay.

99mTc-labeled 1-thio-beta-D-glucose (99mTc-1-TG) was synthesized under different ligand concentrations. 1-Thio-beta-D-glucose (1-TG) showed different chemical properties and higher stability at acid pH as compared to neutral and basic pH. Under different ligand concentrations, 99mTc-1-TG was obtained with high labeling efficiency of >97%, but the HPLC chromatogram varied with the ligand concentration. The results of a tumor cell uptake assay also depended on the ligand concentration. With the lowest ligand concentration tested (0.5 mg/ml of 1-TG), we obtained the highest uptake. With different glucose and insulin concentrations, 99mTc-1-TG uptake was not significantly different from that of [18F]FDG.