Radiomics signature for the prediction of progression-free survival and radiotherapeutic benefits in pediatric medulloblastoma.

PURPOSE: To develop and validate a radiomics signature for progression-free survival (PFS) and radiotherapeutic benefits in pediatric medulloblastoma. MATERIALS AND METHODS: We retrospectively enrolled 253 consecutive children with medulloblastoma from two hospitals. A total of 1294 radiomic features were extracted from the region of tumor on the T1-weighted and contrast-enhanced T1-weighted (CE-T1w) MRI. Radiomic feature selection and machine learning modelling were performed to build radiomics signature for the prediction of PFS on the training set. Moreover, the prognostic performance of the clinical parameters was investigated for PFS. The Concordance index (a value of 0.5 indicates no predictive discrimination, and a value of 1 indicates perfect predictive discrimination) was used to measure and compare the prognostic performance of these models. RESULTS: The radiomics signature for the prediction of the PFS yielded Concordance indices of 0.711, 0.707, and 0.717 on the training and held-out test sets 1 and 2, respectively. The radiomics nomogram integrating the radiomics signature, age, and metastasis performed better than the nomogram incorporating only clinicopathological factors (C-index, 0.723 vs. 0.665 and 0.722 vs. 0.677 on the held-out test sets 1 and 2, respectively), which was also validated by the good calibration and decision curve analysis. Further analysis demonstrated that patients with lower value of radiomics signature were associated with better clinical outcomes after postoperative radiotherapy (p < 0.001). CONCLUSION: The radiomics signature and nomogram performed well for the prediction of PFS and could stratify patients underwent postoperative radiotherapy into the high- and low-risk groups with significantly different clinical outcomes.

The distinct effects of two imidazolium-based ionic liquids, [C4mim][OAc] and [C6mim][OAc], on the phase behaviours of DPPC.

Ionic liquids (ILs) are potential green solvents with very broad application prospects. Their toxicity and other biological effects are largely related to their hydrophobic properties. In this work, the effects of two imidazolium-based ILs with either a butyl or a hexyl chain, [C4mim][OAc] or [C6mim][OAc], on the phase behaviours of a representative phospholipid, dipalmitoylphosphatidylcholine (DPPC), were examined using synchrotron small- and wide-angle X-ray scattering and differential scanning calorimetry techniques. A series of samples with a lipid : IL molar ratio ranging from 1 : 0 to 1 : 4/1 : 5 were prepared as aqueous dispersions in the form of multi-lamellar vesicles. The two ILs were found to have distinct effects on the phase behaviours of DPPC. For [C4mim][OAc], its effect is very limited. In contrast, for [C6mim][OAc], it could eliminate the pre-transition of DPPC, markedly affect the main phase transition of the lipid, and insert into the DPPC bilayer at gel state to form an interdigitated gel phase. The findings increased our understanding on the biological effects of imidazolium-based ILs and might shed light on the design of novel IL-based antimicrobials.

Community child psychiatric medication experiences measured by an internet-based, prospective parent survey of retail pharmacy customers.

One thousand five hundred parents filling a psychiatric prescription for their 6-18 year old child with a multi-state retail pharmacy chain received a single mailed invitation to complete a detailed online survey. 276 parents responded (18.4%). 60% of children on medications had a parent rated CBCL scale score in the clinically significant range at enrollment (T score ≥65), with a similar frequency of clinically significant CBCL scores through 15 months of survey followup. 47% of medication regimens were noted to be causing persistent side effects. This simple community based data collection method can offer a unique way to investigate naturalistic treatment outcomes.

Transition Mechanism from the Metastable Two-Dimensional Gel to the Stable Three-Dimensional Crystal of Imidazolium-Based Ionic Liquids.

One important quest for making high quality materials with amphiphiles is to understand how a disordered self-assembly changes to a stable crystalline state. Herein, we addressed the basic question by investigating the phase transition mechanism of imidazolium-based ionic liquid (IL) [C16mim]Br, using time-resolved small- and wide-angle X-ray scattering (SAXS-WAXS), differential scanning calorimetry, and Fourier transform infrared spectroscopy techniques. Totally, a hexagonal phase, two lamellar-gel phases, and three lamellar-crystalline phases were observed, showing the special polymorphism of the system. It was demonstrated that at low concentrations the two-dimensional gel phase (Lß1) transforms into the most stable lamellar-crystal phase (Lc3) through two intermediate crystalline phases Lc1 and Lc2. At high concentrations, the Lß1 phase changes to a condensed lamellar gel phase (Lß2) before changing to Lc2 and eventually to Lc3. Comparative studies using [C16mim]Cl and [C16mim]NO3 unveiled that the interactions between the counterions and the headgroups of the IL, as well as the dehydration process, govern the nucleation process of Lc3 and thus the formation of the crystal. The in-depth investigation on the transition mechanism and the phase polymorphism in the present work advances our understanding of the crystallization of amphiphilic ionic liquids in dispersions and would promote future applications.

Free-Standing Two-Dimensional Crystals Formed from Self-Assembled Ionic Liquids.

The fabrication of two-dimensional crystals (2DCs) has attracted very large interest because it creates materials with various surface structural features and special surface properties. Normally, this is limited to sheets networked together with strong covalent or coordination bonds. Against this understanding, we discovered macroscopic scale free-standing 2DCs in the aqueous dispersions of [Cnmim]X (X = Br, NO3; n = 14, 16, 18) using simultaneous synchrotron small- and wide-angle X-ray scattering techniques. On the other hand, the 2DCs are also a kind of novel hydrogel holding water content up to 98 wt %. This unusual phenomenon is attributed to the weak interactions between imidazole headgroups and counterions. The observation reported in this work is expected to contribute to theorists in their pursuit of the general principles governing the stability of 2D materials. It may also enlighten experimentalists in designing new free-standing 2DCs for various applications.

Cholesterol Protects the Liquid-Ordered Phase of Raft Model Membranes from the Destructive Effect of Ionic Liquids.

Ionic liquids (ILs), although being a class of promising green solvents, have received many reports on the toxicity to living organisms. In this work, aiming at elucidating the disruptive effect of ILs to cell membrane lipid rafts, we investigated the effect of three 1-octylimidazolium-based ILs on the properties of the liquid ordered phase (Lo, a commonly used lipid raft model) of egg sphingomyelin (SM)-cholesterol model membrane. We found that, in the absence of cholesterol, a very low IL:SM molar ratio of 0.01:1 could disrupt the integrity of the bilayer structure. In sharp contrast, the presence of cholesterol in lipid bilayers helps the Lo phase resist the damaging effect of the ILs. For the role of the IL headgroup, we found that the mono- and trisubstituted species show a stronger destructive effect on the structures of the model rafts than the commonly used disubstituted counterpart.

Transition Mechanism from Nonlamellar to Well-Ordered Lamellar Phases: Is the Lamellar Liquid-Crystal Phase a Must?

Understanding the self-assembly mechanisms of amphiphilic molecules in solutions and regulating their phase behaviors are of primary significance for their applications. To challenge the reported direct phase transitions from nonlamellar to ordered lamellar phases, the self-assembly and phase behavior of the 1-hexadecyl-3-methylimidazolium chloride aqueous dispersions were studied using a strategy of isothermal incubation after the temperature jump. A disordered lamellar phase (identified as the lamellar liquid-crystal (Lα) phase), serving as an intermediate, was found to bridge the transition from a spherical micellar (M) phase to a lamellar-gel (Lß) phase. Meanwhile, the nonsynchronicity in the tail and headgroup regions of the ionic liquid surfactant during the transition process was also unveiled, with the former being prior to the latter. The in-depth understanding of the self-assembly mechanisms may help push forward the related applications in the future.

Effect of Imidazolium-Based Ionic Liquids on the Structure and Phase Behavior of Palmitoyl-oleoyl-phosphatidylethanolamine.

Among various applications, ionic liquids (ILs) have been used as antimicrobial agents in laboratories, possibly through induction of the leakage of bacteria. A molecular-level understanding of the mechanism that describes how ILs enhance the permeation of membranes is still lacking. In this study, the effects of imidazolium-based ILs with different alky chain lengths on the structure and phase behavior of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE), which is a representative bacteria-membrane-rich lipid, have been investigated. By employing differential scanning calorimetry and synchrotron small- and wide-angle X-ray scattering techniques, we found that ILs with longer alkyl chains influenced the phase behavior more effectively, and lower IL concentrations are needed to induce phase separation for both lamellar liquid crystalline phase and nonlamellar inverted hexagonal phase of POPE. Interestingly, the IL with an alkyl chain of 12 carbon atoms ([C12mim]Cl) shows a difference. It exhibits a stronger disturbing effect on the POPE bilayer structure than [C16mim]Cl, indicating that the ability of ILs to influence the membrane structures is dependent not only on the alkyl chain length of ILs, but also on the degree of matching of the alkyl chain lengths of ILs and lipids. The new lamellar and nonlamellar structures induced by ILs both have smaller repeat distances than that of pure POPE, implying thinner membrane structures. Data of the fluorescence-based vesicle dye leakage assay are consistent with these results, particularly the defects caused by IL-induced phase separation can enhance the membrane permeability markedly. The present work may shed light on our understanding of the antimicrobial mechanism of ILs.