Notes

Checking out inter-subject anatomic variability utilizing a populace of patient-specific femurs plus a stats shape as well as depth model.
The growing demand for tailored nonlinearity calls for a structure with unusual phase discontinuity that allows the realization of nonlinear optical chirality, holographic imaging, and nonlinear wavefront control. Transition-metal dichalcogenide (TMDC) monolayers offer giant optical nonlinearity within a few-angstrom thickness, but limitations in optical absorption and domain size impose restriction on wavefront control of nonlinear emissions using classical light sources. In contrast, noble metal-based plasmonic nanosieves support giant field enhancements and precise nonlinear phase control, with hundred-nanometer pixel-level resolution; however, they suffer from intrinsically weak nonlinear susceptibility. Here, we report a multifunctional nonlinear interface by integrating TMDC monolayers with plasmonic nanosieves, yielding drastically different nonlinear functionalities that cannot be accessed by either constituent. Such a hybrid nonlinear interface allows second-harmonic (SH) orbital angular momentum (OAM) generation, beam steering, versatile polarization control, and holograms, with an effective SH nonlinearity χ (2) of ~25 nm/V. This designer platform synergizes the TMDC monolayer and plasmonic nanosieves to empower tunable geometric phases and large field enhancement, paving the way toward multifunctional and ultracompact nonlinear optical devices. Copyright © 2020 Xuanmiao Hong et al.Vanadium oxides have recently attracted widespread attention due to their unique advantages and have demonstrated promising chemical and physical properties for energy storage. This work develops a mild and efficient method to stereoassemble hollow V2O5@FeOOH heterostructured nanoflowers with thin nanosheets. These dual-phased architectures possess multiple lithiation voltage plateau and well-defined heterointerfaces facilitating efficient charge transfer, mass diffusion, and self-reconstruction with volumetric strain. As a proof of concept, the resulting V2O5@FeOOH hollow nanoflowers as an anode material for lithium-ion batteries (LIBs) realize high-specific capacities, long lifespans, and superior rate capabilities, e.g., maintaining a specific capacity as high as 985 mAh g-1 at 200 mA g-1 with good cyclability. Copyright © 2020 Yao Zhang et al.In this study, we used a novel imaging technique, DTI (diffusion tensor imaging)-driven tensor-based morphometry, to investigate brain anatomy in subjects diagnosed with Moebius syndrome (n = 21), other congenital facial weakness disorders (n = 9) and healthy controls (n = 15). First, we selected a subgroup of subjects who satisfied the minimum diagnostic criteria for Moebius syndrome with only mild additional neurological findings. Compared to controls, in this cohort, we found a small region of highly significant volumetric reduction in the paramedian pontine reticular formation and the medial longitudinal fasciculus, important structures for the initiation and coordination of conjugate horizontal gaze. Subsequently, we tested if volume measurements from this region could help differentiate individual subjects of the different cohorts that were included in our study. We found that this region allowed discriminating Moebius syndrome subjects from congenital facial weakness disorders and healthy controls with pathways and/or brainstem nuclei in other neurological disorders. Published by Oxford University Press on behalf of the Guarantors of Brain 2020. This work is written by US Government employees and is in the public domain in the US.Aging-related protein misfolding and aggregation may play critical roles in the pathogenesis of numerous diseases. In the brain, extracellular aggregated amyloid-β (Aβ) is closely related to the death of neurons in individuals with Alzheimer's disease (AD). Albumin-Aβ binding is important in preventing Aβ fibril aggregation. However, because albumin is the most abundant and important antioxidant in the circulation, aging-related oxidative stress could have a significant effect on the molecular conformation and binding capacities of albumin. To investigate the link between misfolded albumin and AD, we developed fluorescent assays to determine the effects of misfolded albumin on membrane integrity in the presence of a lipolytic, inflammatory response-like enzyme, secretory phospholipase A2 (sPLA2). We found that misfolded albumin increased degradation of phospholipids in highly fluid bilayer membranes in the presence of sPLA2 due to hydrophobic effects of misfolded albumin. High amounts of misfolded albumin were present in sera of elderly (average 74 years) versus young (average 24 years) subjects (p  less then  0.0001). Albumin in cerebrospinal fluid (CSF) of elderly subjects, though present in small concentrations, had a 2- to 3-fold increased capacity to promote sPLA2-catalyzed membrane phospholipid degradation as compared with the same amount of albumin in serum (p  less then  0.0001). In addition, the fatty acid binding capacity of albumin in CSF from female subjects was considerably lower than values obtained for men, especially for individuals diagnosed with AD (p = 0.0006). This study suggests that inflammation, misfolded albumin and/or other dysfunctional proteins, and changes in membrane fluidity could alter cell membrane integrity and homeostasis and contribute to the pathogenesis of aging-related dementia and AD. © 2020 – IOS Press and the authors. All rights reserved.A 69-year-old right-handed woman developed difficulty naming objects and word-finding. The clinical features of language disorder and predominant atrophy on MRI and predominant hypoperfusion on 123I-IMP SPECT in the left temporo-parietal junction area were consistent with the diagnostic criteria for the logopenic variant of primary progressive aphasia (lvPPA). Neurological examination showed slight right-side rigidity and resting tremor (UPDRS-III 4). 123I-FP-CIT SPECT showed presynaptic dopamine transporter reduction in the posterior putamina with left-side predominance. The odor-stick identification test for Japanese exhibited complete loss of the sense of smell (anosmia). These findings suggest that lvPPA may be accompanied by parkinsonism and anosmia. © 2020 – IOS Press and the authors. All rights reserved.Public health addresses child maltreatment and other adverse childhood experiences by focusing primarily on preventing them from happening in the first place; understanding and addressing their individual, relational, community, and societal causes using the best available scientific evidence; and engaging in large-scale, multi-sector partnerships. Such large scale efforts require bringing together a compelling narrative, relationships, and strategy. This article describes how the Centers for Disease Control and Prevention used a public health approach to develop a narrative, relationships, and strategy to prevent child maltreatment.Background NUT midline carcinoma, renamed NUT carcinoma (NC), is an aggressive squamous cancer defined by rearrangement of the NUTM1 gene. Although a subset of patients can be cured, for the majority of patients the prognosis is grim. We sought to classify patients into risk groups based on molecular and clinicopathologic factors at the time of diagnosis. Methods Clinicopathologic variables and survival outcomes were extracted for a total of 141 NC patients from the NUT midline carcinoma Registry using questionnaires and medical records. Translocation type was identified by molecular analyses. Survival tree regression analysis was performed to determine risk factors associated with overall survival (OS). Results For 141 patients, the median age at diagnosis was 23.6 years. Fifty-one percent had thoracic origin compared with 49% nonthoracic sites (41% head and neck, 6% bone or soft tissue, 1% other). The median OS was 6.5 months (95% confidence interval [CI] = 5.8 to 9.1 months). Most patients had the BRD4-NUTM1 fusion (78%), followed by BRD3-NUTM1 (15%) and NSD3-NUTM1 (6%). Survival tree regression identified three statistically distinct risk groups among 124 patients classified by anatomical site and genetics group A is nonthoracic primary, BRD3-, or NSD3-NUT (n = 12, median OS = 36.5 months, 95% CI = 12.5 to not reported months); group B is nonthoracic primary, BRD4-NUT (n = 45, median OS = 10 months, 95% CI = 7 to 14.6 months); and group C is thoracic primary (n = 67, median OS = 4.4 months, 95% CI = 3.5 to 5.6 months). Only groups A and B had long-term (≥3 years, n = 12) survivors. Conclusions We identify three risk groups defined by anatomic site and NUT fusion type. Nonthoracic primary with non-BRD4-NUT fusion confers the best prognosis, followed by nonthoracic primary with BRD4-NUT. Thoracic NC patients, regardless of the NUT fusion, have the worst survival. AT7867 © The Author(s) 2019. Published by Oxford University Press.Background Bromodomain and extra-terminal domain proteins are promising epigenetic anticancer drug targets. This first-in-human study evaluated the safety, recommended phase II dose, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the bromodomain and extra-terminal domain inhibitor molibresib (GSK525762) in patients with nuclear protein in testis (NUT) carcinoma (NC) and other solid tumors. Methods This was a phase I and II, open-label, dose-escalation study. Molibresib was administered orally once daily. Single-patient dose escalation (from 2 mg/d) was conducted until the first instance of grade 2 or higher drug-related toxicity, followed by a 3 + 3 design. Pharmacokinetic parameters were obtained during weeks 1 and 3. Circulating monocyte chemoattractant protein-1 levels were measured as a pharmacodynamic biomarker. Results Sixty-five patients received molibresib. During dose escalation, 11% experienced dose-limiting toxicities, including six instances of grade 4 thrombocytopenia, ess.Background Hyperinsulinemia, high insulin-like growth factor 1 (IGF1) levels, and low IGF binding protein 1 (IGFBP1) levels have been implicated in the relationship between obesity and increased risk of colorectal cancer (CRC). However, it remains inconclusive whether circulating biomarkers of insulin and the IGF axis are associated with conventional adenoma and serrated polyp, the two distinct groups of CRC precursors. Methods We prospectively examined the associations of plasma C-peptide, IGF1, IGFBP1, IGFBP3, and IGF1 to IGFBP3 ratio with conventional adenoma and serrated polyp among 11 072 women from the Nurses' Health Studies. Multivariable logistic regression was used to calculate the odds ratio (OR) per 1-SD increase in each biomarker for overall risk of conventional adenoma and serrated polyp and according to polyp feature. Results During 20 years of follow-up, we documented 1234 conventional adenomas and 914 serrated polyps. After adjusting for various lifestyle factors (including body mass index), higher concentrations of IGFBP1 were associated with lower risk of serrated polyp (OR = 0.84, 95% confidence interval = 0.75 to 0.95, P = .005). The association was particularly strong for large serrated polyp (≥10 mm) located in the distal colon and rectum (OR = 0.59, 95% confidence interval = 0.39 to 0.87, P = .01). In contrast, we did not find any statistically significant association between the biomarkers and conventional adenoma. Conclusions A higher plasma level of IGFBP1 was associated with lower risk of serrated polyp. Our findings support a potential role of IGFBP1 in the serrated pathway of CRC in women. © The Author(s) 2019. Published by Oxford University Press.
My Website: https://www.selleckchem.com/products/AT7867.html