Altered Topological Structure of the Brain White Matter in Maltreated Children through Topological Data Analysis

Childhood maltreatment may adversely affect brain development and consequently influence behavioral, emotional, and psychological patterns during adulthood. In this study, we propose an analytical pipeline for modeling the altered topological structure of brain white matter in maltreated and typically developing children. We perform topological data analysis (TDA) to assess the alteration in the global topology of the brain white-matter structural covariance network among children. We use persistent homology, an algebraic technique in TDA, to analyze topological features in the brain covariance networks constructed from structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). We develop a novel framework for statistical inference based on the Wasserstein distance to assess the significance of the observed topological differences. Using these methods in comparing maltreated children to a typically developing control group, we find that maltreatment may increase homogeneity in white matter structures and thus induce higher correlations in the structural covariance; this is reflected in the topological profile. Our findings strongly suggest that TDA can be a valuable framework to model altered topological structures of the brain. The MATLAB codes and processed data used in this study can be found at https://github.com/laplcebeltrami/maltreated

Global perspective on training and staffing for paediatric cardiac critical care

AbstractThis manuscript provides a global perspective on physician and nursing education and training in paediatric cardiac critical care, including available resources and delivery of care models with representatives from several regions of the world including Africa, Israel, Asia, Australasia, Europe, South America, and the United States of America

NMDA Receptor Antibodies and Neuropsychiatric Symptoms in Parkinson's Disease

OBJECTIVE: N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoantibody-mediated neurological syndrome with prominent cognitive and neuropsychiatric symptoms. The clinical relevance of NMDAR antibodies outside the context of encephalitis was assessed in this study. METHODS: Plasma from patients with Parkinson's disease (PD) (N=108) and healthy control subjects (N=89) was screened at baseline for immunoglobulin A (IgA), IgM, and IgG NMDAR antibodies, phosphorylated tau 181 (p-tau181), and the neuroaxonal injury marker neurofilament light (NfL). Clinical assessment of the patients included measures of cognition (Mini-Mental State Examination [MMSE]) and neuropsychiatric symptoms (Hospital Anxiety and Depression Scale; Non-Motor Symptoms Scale for Parkinson's Disease). A subgroup of patients (N=61) was followed annually for up to 6 years. RESULTS: Ten (9%) patients with PD tested positive for NMDAR antibodies (IgA, N=5; IgM, N=6; IgG, N=0), and three (3%) healthy control subjects had IgM NMDAR antibodies; IgA NMDAR antibodies were detected significantly more commonly among patients with PD than healthy control subjects (χ2=4.23, df=1, p=0.04). Age, gender, and disease duration were not associated with NMDAR antibody positivity. Longitudinally, antibody-positive patients had significantly greater decline in annual MMSE scores when the analyses were adjusted for education, age, disease duration, p-tau181, NfL, and follow-up duration (adjusted R2=0.26, p=0.01). Neuropsychiatric symptoms were not associated with antibody status, and no associations were seen between NMDAR antibodies and p-tau181 or NfL levels. CONCLUSIONS: NMDAR antibodies were associated with greater cognitive impairment over time in patients with PD, independent of other pathological biomarkers, suggesting a potential contribution of these antibodies to cognitive decline in PD

Unidimensionality of the Strengths and Vulnerabilities Scales in the Short-Term Assessment of Risk and Treatability (START)

The Short-Term Assessment of Risk and Treatability (START) is a 20-item structured professional judgment instrument for assessing dynamic risk in mental health services. Much of the START research literature examines the relationship between Strengths and Vulnerabilities sub-scale total scores and various adverse outcomes including violence. This assumes that the two sub-scales have the psychometric property of unidimensionality i.e. all the items cluster together as a measure of a single construct. Such assumed unidimensionality is a necessary condition for any analyses based on scale “total score” and the widespread use of scores summated in this way in research studies may obscure more specific clusters of items within each sub-scale. This multinational study examined START assessments (n = 685) conducted in four forensic services in Scandinavia and the UK using principal component analysis. It was found that all but three Strengths items (Substance Use, Social Support and Material Resources) and all but four Vulnerabilities items (Substance Use, Social Support, Material Resources and Self care) loaded >0.5 on the expected component. This indicates a unidimensional structure underlying the START and provides empirical support from a large multinational sample for the widespread use of summated Strengths and Vulnerabilities scores in forensic psychiatric risk research

High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling

Notch-driven expression of IGF1R promotes the growth, viability, and transplantability of T-ALL cells

Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism

Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.German Science Foundation (Grant FE1185)National Institutes of Health (U.S.)Glenn Foundation for Medical ResearchNational Institutes of Health (U.S.) (Grant 5-P50-090381-09)National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)Burroughs Wellcome FundSmith Family FoundationDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.) (Grant 1R01DK075850-01)National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

Precise Measurements of Self-absorbed Rising Reverse Shock Emission from Gamma-ray Burst 221009A

The deaths of massive stars are sometimes accompanied by the launch of highly relativistic and collimated jets. If the jet is pointed towards Earth, we observe a "prompt" gamma-ray burst due to internal shocks or magnetic reconnection events within the jet, followed by a long-lived broadband synchrotron afterglow as the jet interacts with the circum-burst material. While there is solid observational evidence that emission from multiple shocks contributes to the afterglow signature, detailed studies of the reverse shock, which travels back into the explosion ejecta, are hampered by a lack of early-time observations, particularly in the radio band. We present rapid follow-up radio observations of the exceptionally bright gamma-ray burst GRB 221009A which reveal an optically thick rising component from the reverse shock in unprecedented detail both temporally and in frequency space. From this, we are able to constrain the size, Lorentz factor, and internal energy of the outflow while providing accurate predictions for the location of the peak frequency of the reverse shock in the first few hours after the burst.Comment: 11 figures, 4 table

Lipidome analysis of rotavirus-infected cells confirms the close interaction of lipid droplets with viroplasms

10.1099/vir.0.049635-0Journal of General Virology94PART71576-158