Methods for extending working distance using modified photonic crystal for near-field lithography.

Near-field lithography has evident advantages in fabricating super-resolution nano-patterns. However, the working distance (WD) is limited due to the exponential decay characteristic of the evanescent waves. Here, we proposed a novel photolithography method based on a modified photonic crystal (PC), where a defect layer is embedded into the all-dielectric multilayer structure. It is shown that this design can amend the photonic band gap and enhance the desired high-kwaves dramatically, then the WD in air conditions could be extended greatly, which would drastically relax the engineering challenges for introducing the near-field lithography into real-world manufacturing applications. Typically, deep subwavelength patterns with a half-pitch of 32 nm (i.e.,λ/6) could be formed in photoresist layer at an air WD of 100 nm. Moreover, it is revealed that diversified two-dimensional patterns could be produced with a single exposure using linear polarized light. The analyses indicate that this improved dielectric PC is applicable for near-field lithography to produce super-resolution periodic patterns with large WD, strong field intensity, and great uniformity.

Aberrant gray matter structure in neurosyphilis without conventional MRI abnormality: a pilot study with voxel and surface-based morphology.

BACKGROUND: The underlying mechanism of neurosyphilis was not fully understood. PURPOSE: To assess gray matter (GM) microstructure in patients with early-stage neurosyphilis without overt conventional magnetic resonance imaging (MRI) abnormality using voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses. MATERIAL AND METHODS: Three-dimensional high-resolution T1-weighted imaging data from 19 individuals with neurosyphilis and 19 healthy controls were analyzed. A battery of neuropsychological tests was performed before each MRI examination. The differences of GM volume and cerebral cortical morphological data between the two groups were compared. The correlations between MRI metrics and neuropsychology/laboratory tests in the patient group were investigated. RESULTS: Regional decreased GM volumes in patients with neurosyphilis were found in the left frontal cortices (Rolandic operculum, middle frontal, and precentral) and bilateral temporal/occipital cortices (bilateral middle temporal, left lingual, and right middle occipital) (P < 0.05, FDR correction). SBM analysis showed significant cortical thickness reduction in the right medial orbitofrontal lobe, and reduced gyrification index in the left insula in patients with neurosyphilis (P < 0.05, FDR correction). Additionally, in the patient group, the GM volume in the middle frontal gyrus, the cortical thickness of right medial orbitofrontal lobe, and the gyrification index in the left insula were negatively correlated to the number connection test-A scores. The gyrification index was also negatively correlated to cerebrospinal fluid white blood cell count. CONCLUSION: Early-stage neurosyphilis without conventional MRI abnormality presented regional GM volume reduction and cortical morphological changes, which might be related to cognitive impairment and intra-cranial infection. VBM and SBM analyses might be useful for understanding the underlying neural trait of neurosyphilis.

[Latest Findings on Prediction and Prevention of Preeclampsia].

Preeclampsia, a progressive disease involving multiple systems, afflicts pregnancy specifically. It contributes to severe maternal and perinatal morbidity and mortality. It has been reported that preeclampsia initiates from a mismatch between the utero-placental supply and demand, which subsequently triggers the release of placental syncytiotrophoblast stress-derived factors and an imbalance of proangiogenic/antiangiogenic factors, eventually causing maternal systemic endothelial lesions and systemic inflammatory response. Currently, treatments available for preeclampsia are very limited in number. Hence, prediction and prevention carry special significance. Herein, we reviewed the current understanding of preeclampsia, especially findings on the prediction and prevention of preeclampsia published within the past 5 years. We discussed the Fetal Medicine Foundation (FMF) screening model based on placental growth factor (PlGF) and the effects of aspirin, calcium, exercise, and termination of pregnancy in preventing preeclampsia. The efficacy and safety of other new preventive measures still need further validation.

In Situ Surface Structures of PdAg Catalyst and Their Influence on Acetylene Semihydrogenation Revealed by Machine Learning and Experiment.

PdAg alloy is an industrial catalyst for acetylene-selective hydrogenation in excess ethene. While significant efforts have been devoted to increase the selectivity, there has been little progress in the catalyst performance at low temperatures. Here by combining a machine-learning atomic simulation and catalysis experiment, we clarify the surface status of PdAg alloy catalyst under the reaction conditions and screen out a rutile-TiO2 supported Pd1Ag3 catalyst with high performance: i.e., 85% selectivity at >96% acetylene conversion over a 100 h period in an experiment. The machine-learning global potential energy surface exploration determines the Pd-Ag-H bulk and surface phase diagrams under the reaction conditions, which reveals two key bulk compositions, Pd1Ag1 (R3̅m) and Pd1Ag3 (Pm3̅m), and quantifies the surface structures with varied Pd:Ag ratios under the reaction conditions. We show that the catalyst activity is controlled by the PdAg patterns on the (111) surface that are variable under reaction conditions, but the selectivity is largely determined by the amount of Pd exposure on the (100) surface. These insights provide the fundamental basis for the rational design of a better catalyst via three measures: (i) controlling the Pd:Ag ratio at 1:3, (ii) reducing the nanoparticle size to limit PdAg local patterns, (iii) searching for active supports to terminate the (100) facets.

Energy landscape of Au13: a global view of structure transformation.

It has long been a challenge in physics and chemistry to acquire a global picture of the energy landscape of a specific material, as well as the kinetic transformation process between configurations of interest. Here we have presented a comprehensive approach to deal with the structure transformation problem, along with the illustration of the energy landscape, as exemplified with the case of Au13. A configuration space based on interatomic distances was proposed and demonstrated to have a strong correlation between structure and energy, with application in structure analysis to screen for trial transition pathways. As several representative configurations and their transition pathways ascertained and by projecting on a plane, a visual two-dimensional contour map was sketched revealing the unique energy landscape of Au13. It shows that the 2D and 3D clusters form two funnels in the high-dimensional configuration space, with a transition pathway with a 0.976 eV barrier bridging them.

Two-Dimensional Semiconducting Boron Monolayers.

The two-dimensional boron monolayers were reported to be metallic both in previous theoretical predictions and experimental observations. Unexpectedly, we have first found a family of boron monolayers with the novel semiconducting property as confirmed by the first-principles calculations with the quasi-particle G0W0 approach. We demonstrate that the connected network of hexagonal vacancies dominates the gap opening for both the in-plane s+px,y and pz orbitals, with which various semiconducting boron monolayers are designed to realize the band gap engineering for the potential applications in electronic devices. The semiconducting boron monolayers in our predictions are expected to be synthesized on the proper substrates, due to the similar stabilities to the ones observed experimentally.

Geometrical eigen-subspace framework based molecular conformation representation for efficient structure recognition and comparison.

We have developed an extended distance matrix approach to study the molecular geometric configuration through spectral decomposition. It is shown that the positions of all atoms in the eigen-space can be specified precisely by their eigen-coordinates, while the refined atomic eigen-subspace projection array adopted in our approach is demonstrated to be a competent invariant in structure comparison. Furthermore, a visual eigen-subspace projection function (EPF) is derived to characterize the surrounding configuration of an atom naturally. A complete set of atomic EPFs constitute an intrinsic representation of molecular conformation, based on which the interatomic EPF distance and intermolecular EPF distance can be reasonably defined. Exemplified with a few cases, the intermolecular EPF distance shows exceptional rationality and efficiency in structure recognition and comparison.

An intrinsic representation of atomic structure: From clusters to periodic systems.

We have improved our distance matrix and eigen-subspace projection function (EPF) [X.-T. Li et al., J. Chem. Phys. 146, 154108 (2017)] to describe the atomic structure for periodic systems. Depicting the local structure of an atom, the EPF turns out to be invariant with respect to the choices of the unit cell and coordinate frame, leading to an intrinsic representation of the crystal with a set of EPFs of the nontrivial atoms. The difference of EPFs reveals the difference of atoms in local structure, while the accumulated difference between two sets of EPFs can be taken as the distance between configurations. Exemplified with the cases of carbon allotropes and boron sheets, our EPF approach shows exceptional rationality and efficiency to distinguish the atomic structures, which is crucial in structure recognition, comparison, and analysis.

Evaluation of two intervention models on contraceptive attitudes and behaviors among nulliparous women in Shanghai, China: a clustered randomized controlled trial.

BACKGROUND: With increasing acceptance of premarital sex among young Chinese women, the rates of unintended pregnancies and induced abortions are becoming alarmingly high, suggesting the needs of educating women with adequate contraceptive knowledge and providing them with accessible contraceptive services. Previous studies have shown that knowledge and attitudes towards contraception could be modified through intervention strategies. This study aimed to evaluate the effects of two community intervention models on modifying contraceptive attitudes and behaviors among nulliparous women. METHODS: In this clustered randomized controlled trial, nulliparous women aged 18-40 years from 18 communities were enrolled and randomized to either the traditional community intervention model (TC model) or the more comprehensive new community-based intervention model (NC model) with a ratio of 1:2. Contraceptive attitudes and behaviors were assessed before and after the interventions. RESULTS: A total of 901 nulliparous women were followed. The most common contraceptive method in both groups was condom (approximately 80%) before or after interventions. The rates of using effective contraceptive methods were very low (<5%) even after the intervention. Comparing the NC with TC group, the adjusted ORs and 95% CIs regarding natural family planning, emergency contraceptive usage and short-acting OCPs were1.53 (95% CI: 1.11-2.13), 2.87 (95% CI: 2.05-4.02), and 2.71 (95% CI: 1.65-4.47), respectively; while the ORs and 95%CIs of gynecological examination and contraceptive use were 2.31 (95% CI: 1.63-3.27) and 2.89 (95% CI: 1.98-4.23), respectively. No statistical significant difference was found for the use of effective contraceptive methods at post-intervention among the two models. CONCLUSIONS: High proportions of nulliparous women held negative attitudes and behaviors towards effective contraceptive methods. The NC model, integrating existing health resources, had more positive influence than the TC model on the favorable contraceptive attitudes and behaviors towards the use of any contraceptive methods, but had limited impact on the use of effective contraceptive methods. Our study suggested the feasibility of applying the NC model in Shanghai. Interventions on contraceptive attitudes and behaviors should base on the existing health service system, synthesize resources and selectively apply to populations with distinct characteristics.

Survey on the Implementation of Preconception Care in Shanghai, China.

BACKGROUND: Recently, the Chinese government has promoted preconception care (PCC) to prevent birth defects. The objective of this study was to evaluate the implementation of PCC in Shanghai, China, following a 3-year municipal project providing 'Free Pre-pregnancy Health Evaluation Services' to 20 000 residents. METHODS: A retrospective questionnaire survey was undertaken among 12 309 pregnant women and 8997 of their partners during their initial prenatal visit in six hospitals with the most births in Shanghai. RESULTS: A total of 90% (n = 11 113) of the women and 87% (n = 7856) of the men were aware of PCC, and 40% (n = 4890) of the women and 35% (n = 3185) of the men had previously participated in PCC. Logistic regression showed that PCC participants were more likely to have a planned pregnancy, receive support from their partner for PCC services, were older, and have higher educational attainment and higher household incomes. Regardless of gender, there were significant differences between the participating and non-participating groups in terms of prepregnancy changes in lifestyle and behaviour, such as folic acid supplementation, smoking cessation (for men only), avoiding passive smoking, abstaining from alcohol/drugs, and rubella/hepatitis B immunity. CONCLUSIONS: The government-led efforts proved to be effective in promoting PCC participation and positive lifestyle and behavioural changes in couples of childbearing age. Future efforts should target couples who are young, poorly educated, and/or from low-income families. Strategies must ensure that the couples' knowledge of and positive attitudes toward PCC are translated into their practical participation in PCC.

[Full-field and automatic methodology of spectral calibration for PGP imaging spectrometer].

In order to analyze spectral data quantitatively which is obtained by prism-grating-prism imaging spectrometer, spectral calibration is required in order to determine spectral characteristics of PGP imaging spectrometer, such as the center wavelength of every spectral channel, spectral resolution and spectral bending. A spectral calibration system of full field based on collimated monochromatic light method is designed. Spherical mirror is used to provide collimated light, and a freely sliding and rotating folding mirror is adopted to change the angle of incident light in order to realize full field and automatic calibration of imaging spectrometer. Experiments of spectral calibration have been done for PGP imaging spectrometer to obtain parameters of spectral performance, and accuracy analysis combined with the structural features of the entire spectral calibration system have been done. Analysis results indicate that spectral calibration accuracy of the calibration system reaches 0.1 nm, and the bandwidth accuracy reaches 1.3%. The calibration system has merits of small size, better commonality, high precision and so on, and because of adopting the control of automation, the additional errors which are caused by human are avoided. The calibration system can be used for spectral calibration of other imaging spectrometers whose structures are similar to PGP.

Incarcerated umbilical hernia in a patient with cirrhotic ascites in combination with chronic lymphocytic leukemia: a case report.

Umbilical hernia is a common type of extra-abdominal hernia in adults. However, chronic granulocytic leukemia in combination with cirrhotic ascites and renal insufficiency is less common. The patient reported here had both indications and contraindications for emergency surgery; therefore, the treatment options were subject to debate. We report the case of a man in his 60s who had a strangulated umbilical hernia, with overlying purple-colored infected and necrotic skin. The area was painful, but his bowel movements were normal. Patients underwent comprehensive conservative management, and remote follow-ups via telephone and video conferencing for a period of 60 days, during which the incarcerated contents of the hernia eventually retracted and his pain was relieved, such that there were no longer indications for emergency surgery. In addition, his skin infection disappeared and his quality of life improved, and therefore the treatment outcomes were good. Thus, we provide evidence that not all incarcerated umbilical hernias require emergency surgery, but may respond well to conservative treatment when the contents do not include intestinal loops or other critical organs.

Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes.

Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

[Generation mechanism and control methods of antibiotic and heavy metal resistance genes in poultry waste: A review]. / ç•œç¦½å »æ®–åºŸç‰©ä¸­æŠ—ç”Ÿç´ å’Œé‡é‡‘å±žæŠ—æ€§åŸºå› çš„äº§ç”Ÿæœºåˆ¶å’ŒæŽ§åˆ¶æ–¹æ³•ç ”ç©¶è¿›å±•.

As antibiotics and heavy metals are often mixed in animal feed, their excretion through animal feces would cause bacteria to produce antibiotic resistance genes and heavy metal resistance genes. The pollution of antibiotics resistance gene and heavy metal resistance gene has become a major threat to human health and ecological environment. From the perspective of bacterial evolution, we proposed the importance of bacterial long-term evolution experiments about antibiotics and heavy metals. There is a complex co-selection resistance between antibiotic resistance genes and heavy metal resistance genes, which interact with each other and collectively determine the environmental behavior of bacteria. Horizontal transfer of resistance gene increases its variability in the environment. Mobile genetic elements play an important role in horizontal transfer of resistance gene. As for resistance gene pollution control, advanced oxidation technology has a good resistance gene removal effect. The UV/TiO2 oxidation technology can reduce the abundance of antibiotic resistance genes of 4.7-5.8 log, with an efficiency of >99.99%. Other control strategies, such as the use of Macleaya cordata extract and the combination of bacteriophage and antibiotics, are also of significance for controlling resistance genes.

[Effects of taking estrogen and progestogen after medical abortion on reducing vaginal hemorrhage time: a randomized-controlled trial].

OBJECTIVE: To compare the different effects of taking different kinds and doses of estrogen and progestogen after medical abortion on reducing vaginal hemorrhage time. METHODS: A total of 188 women undergoing medical abortion were recruited and randomized into 3 groups: group A (n = 41) starting marvelon (30 µg ethinylestradiol and 150 µg desogestrel) on the day of abortion for 21 days; group B (n = 53) starting progynova 2 mg/d on the day of abortion for 21 days and taking depogesterone 10 mg/d on the last 5 days; and group C (n = 94) as control. The vaginal hemorrhage time, days to onset of next menses and the outcome of medical abortion were compared. RESULTS: There was no significant difference in the duration of hemorrhage between groups A and C [(20 ± 13) vs (19 ± 11) d, P > 0.05]. But the duration of hemorrhage in group B was significantly shorter than that in group C [(14 ± 7) vs (19 ± 11) d, P < 0.01]. There was no significant difference in the amount of hemorrhage among 3 groups (P > 0.05). The time to onset of first menses was similar between groups A and B [(34 ± 13) vs (30 ± 7) d]. And both were significantly shorter than that in group C [(39 ± 11) d, P < 0.05]. There were 3 (7.32%) incomplete abortions in group A, 4 (7.55%) in group B and 12 (12.77%) in group C (P > 0.05). CONCLUSION: The sequential therapy of estrogen and progestogen after medical abortion may effectively reduce the duration of hemorrhage. And the combined oral contraceptive pills fail to significantly alter the duration of hemorrhage after medical abortion. But both can promote menstrual recovery significantly.

[Effects of human leukocyte antigen-G on p38 mitogen-activated protein kinase signaling pathway in HTR-8/SVneo cell line].

OBJECTIVE: To investigate the role of human leukocyte antigen-G (HLA-G) on the invasion and the molecular mechanism involved in this cellular progress in HTR-8/SVneo cell line. METHODS: There were three groups: groups of transfection, negative control and blank control, which corresponding to treatment by HLA-G specific siRNA, negative siRNA and only lipofectamine 2000 using lipofection technology in HTR-8/SVneo cell line. The efficiency of down-regulated of HLA-G was detected by reverse transcription-polymerase chain reaction and western blot analysis in mRNA and protein level, respectively. Changes of p38 mitogen-activated protein kinases (p-p38MAPK)/p38MAPK protein levels and the cell invasion were respectively detected by western blot analysis and transwell test. RESULTS: (1) The mRNA levels of HLA-G transfection group, negative control group and blank control group were 0.26±0.08, 0.71±0.11, 0.79±0.07, respectively. There was significant difference between transfection group and negative control group (P<0.01), while there was no significant difference between negative control group and blank control group (P>0.05). The efficiencies of down-regulated of HLA-G were (69.8±6.3)%, (14.9±2.2)%, 0 in transfection group, negative control group and blank control group respectively in mRNA level. (2) In protein levels, HLA-G were 0.20±0.15, 0.75±0.12, 0.76±0.21 in transfection group, negative control group and blank control group, respectively. There was significant difference between transfection group and negative control group (P<0.01), whereas there was no significant difference between negative control group and blank control group (P>0.05). The efficiencies of down-regulated of HLA-G were (81.1±14.4)%, (18.0±7.7)%, 0 in transfection group, negative control group and blank control group respectively. (3) The invasive number of transfection group, negative control group and blank control group were 57±38, 364±79 and 260±84, respectively, with a significant difference between transfection group and negative control group (P<0.01). There was no significant difference between negative control group and blank control group (P>0.05). (4) The p-p38MAPK/p38MAPK values of the HLA-G transfection group, negative control group and blank control group were 0.74±0.04, 0.47±0.09 and 0.36±0.21, respectively. HLA-G transfection group was significantly different compared with the other two groups (P<0.01). (5) Without or with SB203580, the p-p38MAPK/p38MAPK values of the HLA-G transfection group were 0.89±0.09 and 0.16±0.04, the values of negative control group and blank control group were 0.76±0.08, 0.14±0.03 and 0.51±0.05, 0.03±0.01, respectively. There was significant difference between without SB203580 and with SB203580 (P<0.01). (6) Without or with SB203580, the invasive number of transfection group were 51±13 and 90±21, respectively, which was significantly different (P<0.01). The invasive number of negative control group and blank control group were 290±52, 298±33 and 290±73, 264±64, respectively, which was no significant difference between without SB203580 and with SB203580 (P>0.05). CONCLUSIONS: HLA-G gene may regulate invasion of trophoblast-derived cell line HTR-8/SVneo via p38MAPK signaling pathway. The lower expression of HLA-G in trophoblast cells may lead to the occurrence of pathologic pregnancy.

[Karyotype analysis of amniotic fluid cells and comparison of chromosomal abnormality rate during second trimester].

OBJECTIVE: To investigate the karyotypes of amniotic fluid cells and compare the incidence of chromosomal abnormality as well as to evaluate the clinical significance of abnormal karyotypes. METHODS: A total of 13 648 pregnant women came to Shanghai Jiai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University to do amniocentesis from September 1998 to November 2010, and 13 795 amniotic fluid specimens were successfully extracted and cultured, thus 13 795 fetuses received karyotype diagnosis. These fetuses were grouped according to different indications. If maternal age was ≥ 35, the fetuses were grouped into the advanced maternal age group (4065); and if maternal serum screening test revealed high-risk of trisomy 18 or trisomy 21, the fetuses were grouped into the high-risk serum screening group (6462); and those with abnormal signs of ultrasound screening were grouped into the abnormal ultrasound signs group (1539); and if either of the parents was with chromosome abnormalities, the fetus was grouped into the paternal/maternal abnormality group (108); whereas the remainder were grouped in other factors group (1621). The amniotic fluid cells were in-situ cultured on coverslips, harvested by conventional G-banded methods, and then analyzed by two doctors. In order to get rapid diagnosis, some pregnant women whose gestational age ≥ 26 weeks accepted fluorescense in situ hybridization (FISH). FISH was done on 78 uncultured amniotic fluid specimens using probes located at chromosome 13, 18, 21, X, Y. Some parents were required to analyze lymphocyte karyotype to help judging the origin of abnormal karyotype. RESULTS: (1) Classification and composition of abnormal karyotypes in each group: a total of 388 abnormal karyotypes were found among 13 795 fetuses, and the abnormal rate was 2.813% (388/13 795). Of the 388 fetuses, aneuploidy was the most common pattern which was up to 59.8% (232/388); autosomal structural abnormality rate was 24.7% (96/388); mosaicism was 12.4% (48/388). Other uncommon abnormal karyotypes included marker chromosome (5/388, 1.3%), sex chromosomal structural abnormality (4/388, 1.0%) and triploid (3/388, 0.8%). Aneuploidy was the most common in most groups except the paternal/maternal abnormality group. There were four cases of rare aneuploid in the advanced maternal age group, the high-risk serum screening group and the abnormal ultrasound signs group respectively. Every type of abnormality could be found in the abnormal ultrasound signs group, and autosomal structural abnormalities were concentrated in paternal/maternal abnormality group. Mosaicism mainly distributed in the high-risk serum screening group, accounting for 20.0% (29/145) of abnormalities in this group. (2) Abnormal types and the incidence: the most common type was trisomy 21 (138/388, 35.6%), followed by autosomal balanced structural rearrangements (80/388, 20.6%), mosaicism (48/388, 12.4%) and trisomy 18 (44/388, 11.3%). Others included non-balanced autosomal structural rearrangements (16/388, 4.1%), 45, X0 (16/388, 4.1%) and 47, XXY (15/388, 3.9%). (3) Lymphocyte karyotype analysis of the couples: parents of 153 fetuses were analyzed to determine the origin of abnormal karyotype. Fifty-eight familial and 95 de novo abnormalities were found. FISH results were the same with G-banding karyotype, and two of these were trisomy 21. CONCLUSIONS: Abnormal karyotype composition is different according to different maternal amniocentisis indications. There is a variety of abnormal karyotypes in the second trimester pregnancy, and the risk of fetal malformation is related with the kind of abnormal karyotype.

Identification and Characterization of Leptomeningeal Metastases Using SPINE, A Web-Based Collaborative Platform.

BACKGROUND AND PURPOSE: Leptomeningeal metastases (LMs) carry a poor prognosis. Existing LM scoring systems show limited reproducibility. We assessed the contribution of education level on the reproducibility of LM scoring using structured planning and implementation of new experiments (SPINE), a novel web-based platform. METHODS: Stringent radiological definitions of LM and a customized interactive scoring system were implemented in SPINE. Five patients with brain LM and 3 patients with spine, but no brain LM, were selected. Each patient's baseline post-contrast T1-weighted brain MRI was analyzed by three attending neuroradiologists, two neuroradiology fellows, and two radiology residents. Raters identified and characterized all LMs based on: (1) location (cerebrum, cerebellum, brainstem, ventricle, and/or cranial nerves); (2) shape (nodular and/or linear/curvilinear); (3) size (≥ or <5mm in two orthogonal diameters); (4) spatial extension (focal or diffuse). Inter-rater agreement and association of LM with patient survival were investigated. RESULTS: On average, 6.5 LMs per case were detected. Forty-nine percent of LMs were cerebral, 77.7% were nodular, 86.6% were focal, and 66% were <5 × 5 mm. Agreement on the total number of LMs and the above-mentioned common LM characteristics was higher between attendings (intra-class correlation [ICC] = 0.8-0.94) than fellows (ICC = 0.6-0.82) or residents (ICC = 0.43-0.73). Agreement on ventricular, cranial nerve, and nodular + linear LM was low even between attendings. The number of brainstem LMs showed significant correlation with survival. CONCLUSION: Structured education using SPINE may improve consistency in LM reporting. Future work should address the impact of the presented approach on the reproducibility of longitudinal analyses directly relevant to the assessment of treatment-response.

Preparation and characterization of freeze-dried 2-methoxyestradiol nanoparticle powders.

Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, a nanoprecipitation-high-frequency ultrasonication technique was adapted to produce drug nanosuspensions. The formulation of 2-methoxyestradiol (2-ME) as nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more 45 times than bulk 2-ME being dissolved in the first 10 min. The increase in vitro dissolution rate may favourably affect bioavailability. The nanosuspension produced was then characterized using particle size determination, zeta potential measurement, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray analysis. Results showed that freeze-dried nanosuspension composed of amorphous particles with a mean particle size of 244 +/- 10.6 nm (polydispersity index of 0.21 +/- 0.02) was obtained. Physical stability studies showed that 2-ME nanosuspension remained homogeneous with slight increase in mean particle size and polydispersity index over a 3-month period.

Standardization of imaging methods for machine learning in neuro-oncology.

Radiomics is a novel technique in which quantitative phenotypes or features are extracted from medical images. Machine learning enables analysis of large quantities of medical imaging data generated by radiomic feature extraction. A growing number of studies based on these methods have developed tools for neuro-oncology applications. Despite the initial promises, many of these imaging tools remain far from clinical implementation. One major limitation hindering the use of these models is their lack of reproducibility when applied across different institutions and clinical settings. In this article, we discuss the importance of standardization of methodology and reporting in our effort to improve reproducibility. Ongoing efforts of standardization for neuro-oncological imaging are reviewed. Challenges related to standardization and potential disadvantages in over-standardization are also described. Ultimately, greater multi-institutional collaborative effort is needed to provide and implement standards for data acquisition and analysis methods to facilitate research results to be interoperable and reliable for integration into different practice environments.