The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study.
To perform chromosomal microarray analysis (CMA) and whole-exome ...sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic.
The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6).
All probands underwent CMA, with WES performed for 95 proband-parent trios.
The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups.
Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). table: see text.
Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.
A Li-ion capacitor (LIC), typically composed of a pre-lithiated negative electrode and an activated-carbon positive electrode, can provide high energy and power density. In this work, we compare the ...electrochemical performances of pre-lithiated graphene nanosheets and conventional graphite as negative electrode materials for LICs. The LICs employing pre-lithiated graphene nanosheets show a specific capacitance of 168.5 F g−1 with 74% capacitance retention at 400 mA g−1 after 300 cycles. Moreover, the capacitors deliver a maximum power density of 222.2 W kg−1 at an energy density of 61.7 Wh kg−1, operated in the voltage range of 2.0–4.0 V. Therefore, pre-lithiated graphene nanosheets are promising negative electrode materials for high power LICs.
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•Pre-lithiated graphene nanosheets are explored for Li-ion capacitors.•The Li-ion capacitors exhibit high energy and power density at high voltages.•Pre-lithiated graphene nanosheets are promising for high power Li-ion capacitors.
A space‐confined “sauna” reaction system is introduced for the simultaneous reduction and functionalization of graphene oxide to unique graphene–sulfur hybrid nanosheets, in which thin layers of ...amorphous sulfur are tightly anchored on the graphene sheet via strong chemical bonding. Upon being used as the cathode material in lithium–sulfur batteries, the as‐synthesized composite shows an excellent electrochemical performance.
Although cancer often is referred to as “a disease of the genes,” it is indisputable that the (epi)genetic properties of individual cancer cells are highly variable, even within the same tumor. ...Hence, preexisting resistant clones will emerge and proliferate after therapeutic selection that targets sensitive clones. Herein, the authors propose that quantitative image analytics, known as “radiomics,” can be used to quantify and characterize this heterogeneity. Virtually every patient with cancer is imaged radiologically. Radiomics is predicated on the beliefs that these images reflect underlying pathophysiologies, and that they can be converted into mineable data for improved diagnosis, prognosis, prediction, and therapy monitoring. In the last decade, the radiomics of cancer has grown from a few laboratories to a worldwide enterprise. During this growth, radiomics has established a convention, wherein a large set of annotated image features (1‐2000 features) are extracted from segmented regions of interest and used to build classifier models to separate individual patients into their appropriate class (eg, indolent vs aggressive disease). An extension of this conventional radiomics is the application of “deep learning,” wherein convolutional neural networks can be used to detect the most informative regions and features without human intervention. A further extension of radiomics involves automatically segmenting informative subregions (“habitats”) within tumors, which can be linked to underlying tumor pathophysiology. The goal of the radiomics enterprise is to provide informed decision support for the practice of precision oncology.
Virtually every patient with cancer is radiologically imaged. The field of radiomics combines quantitative analysis of these images with machine learning to improve diagnosis, prognosis, prediction, and therapy monitoring. This review describes radiomics including novel artificial intelligence methods, and introduces the practice of defining subregions, or “habitats,” within tumors.
Arsenic in groundwater caused the black‐foot disease (BFD) in many countries in the 1950–1960s. It is of great importance to develop a feasible method for removal of arsenic from contaminated ...groundwater in BFD endemic areas. Photocatalytic oxidation of As(III) to less toxic As(V) is, therefore, of significance for preventing any arsenic‐related disease that may occur. By in situ synchrotron X‐ray absorption spectroscopy, the formation of As(V) is related to the expense of As(III) disappearance during photocatalysis by TiO2 nanotubes (TNTs). Under UV/Vis light irradiation, the apparent first‐order rate constant for the photocatalytic oxidation of As(III) to As(V) is 0.0148 min−1. It seems that As(III) can be oxidized with photo‐excited holes while the not‐recombined electrons may be scavenged with O2 in the channels of the well defined TNTs (an opening of 7 nm in diameter). In the absence of O2, on the contrary, As(III) can be reduced to As(0), to some extent. Cu(II) (CuO), as an electron acceptor, was impregnated on the TNTs surfaces in order to gain a better understanding of electron transfer during photocatalysis. It appears that As(III) can be oxidized to As(V) while Cu(II) is reduced to Cu(I) and Cu(0). The molecular‐scale data are very useful in revealing the oxidation states and interconversions of arsenic during the photocatalytic reactions. This work has implications in that the toxicity of arsenic in contaminated groundwater or wastewater can be effectively decreased via solar‐driven photocatalysis, which may facilitate further treatments by coagulation.
The photocatalytic oxidation of As(III) to less toxic As(V) by TiO2 nanotubes studied using in situ synchrotron X‐ray absorption spectroscopy is presented.
Neurosteroids are endogenous modulators of neuronal excitability and nervous system development and are being developed as anesthetic agents and treatments for psychiatric diseases. While gamma ...amino-butyric acid Type A (GABAA) receptors are the primary molecular targets of neurosteroid action, the structural details of neurosteroid binding to these proteins remain ill defined. We synthesized neurosteroid analogue photolabeling reagents in which the photolabeling groups were placed at three positions around the neurosteroid ring structure, enabling identification of binding sites and mapping of neurosteroid orientation within these sites. Using middle-down mass spectrometry (MS), we identified three clusters of photolabeled residues representing three distinct neurosteroid binding sites in the human α1β3 GABAA receptor. Novel intrasubunit binding sites were identified within the transmembrane helical bundles of both the α1 (labeled residues α1-N408, Y415) and β3 (labeled residue β3-Y442) subunits, adjacent to the extracellular domains (ECDs). An intersubunit site (labeled residues β3-L294 and G308) in the interface between the β3(+) and α1(-) subunits of the GABAA receptor pentamer was also identified. Computational docking studies of neurosteroid to the three sites predicted critical residues contributing to neurosteroid interaction with the GABAA receptors. Electrophysiological studies of receptors with mutations based on these predictions (α1-V227W, N408A/Y411F, and Q242L) indicate that both the α1 intrasubunit and β3-α1 intersubunit sites are critical for neurosteroid action.
•Two different thermal conditions are established to explore the lithium-ion battery performance.•Battery pack without BTMS intervention may have an excellent discharging performance.•Battery ...charging performance is independent on the charging temperature ranged from 20 °C to 40 °C.•The irreversible heat can be regarded as the sole heat source term to simplify battery thermal model.
The relationship between lithium-ion battery performance and operating temperature is of significance in designing battery thermal management system (BTMS). In this study, two different thermal conditions, namely constant temperature condition and near-adiabatic condition are established to explore charging/discharging characteristics and heat generation behaviors of the lithium-ion battery with Li(NixCoyAlz)O2 cathode. The objective of creating near-adiabatic condition is to discover the effect of the heat generated by battery itself on charging/discharging characteristics. The experimental results show that the battery charging characteristics are nearly independent on the charging temperature ranged from 20 °C to 40 °C, while the battery charging/discharging performance degrade dramatically for the battery temperature lower than 20 °C. Although the heat generated by battery itself may accelerate battery degradation during cycling due to the adverse effect of excessive temperature, however it improves the discharging performance in a suitable temperature range. This implies that a battery pack may have an excellent discharging performance without BTMS intervention at a moderate discharging rate (e.g., 0.5 C). The irreversible heat could be regarded as the sole heat source term to simplify the battery thermal model due to negligible thermal effect caused by the small amount of reversible heat when the battery is discharged at higher discharging rates.
Introduction
he prevalence of frailty defined by FRAIL-NH varies among different studies in nursing homes, ranging from 19.0% to 75.6%. This study investigated the prevalence of frailty in a nursing ...home in Taiwan using different diagnostic criteria for frailty.
Methods
The 7-item FRAIL-NH scale was used for assessing frailty. There are 7 components: fatigue, resistance, mobility, incontinence or disease, weight loss, eating style and assistance with dressing. Each item is worth 0, 1, or 2 points for a total score of 14 points. We sorted and summarized the patients, according to the number of variables, into the not frail, frail, and most frail groups. Descriptive analysis was applied to understand the basic attributes of the elderly with different degrees of frailty, the influencing factors of frailty, and the occurrence of frailty.
Results
Our final sample included 34 residents. They were aged between 56 and 100 years (mean age 83.91 ± 10.84), and 18 (52.94%) were female. The frail group revealed a higher prevalence of males than of females. The marital status composition of participants was as follows: 2 (5.88%) unmarried, 24 (70.59%) married, and 8 (23.53%) widowed. The mean FRAIL-NH score was 5.79±3.72.
Conclusions
A significant prevalence of frailty defined by FRAIL-NH was observed in a nursing home in Taiwan. Our findings indicate that frailty is an important issue in nursing homes. Further prospective cohort studies using FRAIL-NH evaluation are warranted.
TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) ...therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP–treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 507 cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP–treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies.
Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)–like and unfavorable activated B-cell (ABC)–like subtypes based on gene expression ...signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP.
•DLBCL patients with MYC/BCL2 coexpression demonstrate inferior prognosis and high-risk gene expression signatures.
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