Effect of visual feedback on the occipital-parietal-motor network in Parkinson's disease with freezing of gait.

Freezing of gait (FOG) is an elusive phenomenon that debilitates a large number of Parkinson's disease (PD) patients regardless of stage of disease, medication status, or deep brain stimulation implantation. Sensory feedback cues, especially visual feedback cues, have been shown to alleviate FOG episodes or even prevent episodes from occurring. Here, we examine cortical information flow between occipital, parietal, and motor areas during the pre-movement stage of gait in a PD-with-FOG patient that had a strong positive behavioral response to visual cues, one PD-with-FOG patient without any behavioral response to visual cues, and age-matched healthy controls, before and after training with visual feedback. Results for this case study show differences in cortical information flow between the responding PD-with-FOG patient and the other two subject types, notably, an increased information flow in the beta range. Tentatively suggesting the formation of an alternative cortical sensory-motor pathway during training with visual feedback, these results are proposed as subject for further verification employing larger cohorts of patients

Image analysis reveals molecularly distinct patterns of TILs in NSCLC associated with treatment outcome.

Despite known histological, biological, and clinical differences between lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), relatively little is known about the spatial differences in their corresponding immune contextures. Our study of over 1000 LUAD and LUSC tumors revealed that computationally derived patterns of tumor-infiltrating lymphocytes (TILs) on H&E images were different between LUAD (N = 421) and LUSC (N = 438), with TIL density being prognostic of overall survival in LUAD and spatial arrangement being more prognostically relevant in LUSC. In addition, the LUAD-specific TIL signature was associated with OS in an external validation set of 100 NSCLC treated with more than six different neoadjuvant chemotherapy regimens, and predictive of response to therapy in the clinical trial CA209-057 (n = 303). In LUAD, the prognostic TIL signature was primarily comprised of CD4+ T and CD8+ T cells, whereas in LUSC, the immune patterns were comprised of CD4+ T, CD8+ T, and CD20+ B cells. In both subtypes, prognostic TIL features were associated with transcriptomics-derived immune scores and biological pathways implicated in immune recognition, response, and evasion. Our results suggest the need for histologic subtype-specific TIL-based models for stratifying survival risk and predicting response to therapy. Our findings suggest that predictive models for response to therapy will need to account for the unique morphologic and molecular immune patterns as a function of histologic subtype of NSCLC

System-wide transcriptome damage and tissue identity loss in COVID-19 patients

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections., • Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients • Organ-specific cell types and functional markers are lost in all COVID-19 tissue types • Lung compartment identity loss correlates with SARS-CoV-2 viral loads • COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) , Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung

EEG analysis of gait movement preparation in the normal state and in the abnormal state of Parkinsonʼs disease with freezing of gait /

The cortical control of gait is an important aspect of locomotive function in healthy and diseased states. Here we used electroencephalography (EEG), signal processing, and machine learning methods to capture neural signals related to movement preparation of gait in healthy controls and in Parkinson's disease patients with freezing of gait (FOG). We focused on pre-movement EEG in tasks that required natural ambulation of the subjects through the environment with the ultimate goal of application to brain computer interfaces. First we aimed to predict the intent to start gait before the onset of any movement in normal, healthy individuals, and to distinguish this signal from different actions such as standing and pointing. Wavelets were used as features in LDA classification, which resulted in errors as low as 17% when averaged across nine subjects. The neural signal used for classification mostly consisted of contributions from slow cortical potentials (0.1-1 Hz) with additional, smaller contributions from mu (8-13 Hz) and beta (14-25 Hz) frequency bands from channels located over sensorimotor cortex. We then examined this pre-movement period in subjects who experience freezing of gait (FOG) to determine how PD FOG patients differ from healthy controls in baseline neural activity and how these measures change with visual modulation of the environment. The spectral activity and connectivity in and between occipital, parietal, and motor regions were assessed by using EEG signals recorded at channels Oz, Pz, and Cz in a network analysis of causal information flow. The results suggest possible pathological over-binding of cortical areas important for sensory integration and motor control through increased baseline theta and beta oscillations in freezing of gait patients who respond to visual feedbac

EEG analysis of gait movement preparation in the normal state and in the abnormal state of Parkinsonʼs disease with freezing of gait /

The cortical control of gait is an important aspect of locomotive function in healthy and diseased states. Here we used electroencephalography (EEG), signal processing, and machine learning methods to capture neural signals related to movement preparation of gait in healthy controls and in Parkinson's disease patients with freezing of gait (FOG). We focused on pre-movement EEG in tasks that required natural ambulation of the subjects through the environment with the ultimate goal of application to brain computer interfaces. First we aimed to predict the intent to start gait before the onset of any movement in normal, healthy individuals, and to distinguish this signal from different actions such as standing and pointing. Wavelets were used as features in LDA classification, which resulted in errors as low as 17% when averaged across nine subjects. The neural signal used for classification mostly consisted of contributions from slow cortical potentials (0.1-1 Hz) with additional, smaller contributions from mu (8-13 Hz) and beta (14-25 Hz) frequency bands from channels located over sensorimotor cortex. We then examined this pre-movement period in subjects who experience freezing of gait (FOG) to determine how PD FOG patients differ from healthy controls in baseline neural activity and how these measures change with visual modulation of the environment. The spectral activity and connectivity in and between occipital, parietal, and motor regions were assessed by using EEG signals recorded at channels Oz, Pz, and Cz in a network analysis of causal information flow. The results suggest possible pathological over-binding of cortical areas important for sensory integration and motor control through increased baseline theta and beta oscillations in freezing of gait patients who respond to visual feedbac

Hydration of the folding transition state ensemble of a protein

A complete description of the mechanisms of protein folding requires knowledge of the structural and physical character of the folding transition state ensembles (TSEs). A key question concerning the role of hydration of the hydrophobic core in determining folding mechanisms remains. To address this, we probed the state of hydration of the TSE of staphylococcal nuclease (SNase) by examining the fluorescence-detected pressure-jump relaxation behavior of six SNase variants in which a residue in the hydrophobic core, Val-66, was replaced with polar or ionizable residues (Lys, Arg, His, Asp, Glu, and Asn). Because of a large positive activation volume for folding, the major effect of pressure on the wild-type protein is to decrease the folding rate. By the time wild-type SNase reaches the folding transition state, most water has already been expelled from its hydrophobic core. In contrast, the major effect of pressure on the variant proteins is an increase in the unfolding rate due to a large negative activation volume for unfolding. This results from a significant increase in the level of hydration of the TSE when an internal ionizable group is present. These data confirm that the role of water in the folding reaction can differ from protein to protein and that even a single substitution in a critical position can modulate significantly the properties of the TSE

Effect of visual feedback on the occipital-parietal-motor network in Parkinson's disease with freezing of gait.

Freezing of gait (FOG) is an elusive phenomenon that debilitates a large number of Parkinson's disease (PD) patients regardless of stage of disease, medication status, or deep brain stimulation implantation. Sensory feedback cues, especially visual feedback cues, have been shown to alleviate FOG episodes or even prevent episodes from occurring. Here, we examine cortical information flow between occipital, parietal, and motor areas during the pre-movement stage of gait in a PD-with-FOG patient that had a strong positive behavioral response to visual cues, one PD-with-FOG patient without any behavioral response to visual cues, and age-matched healthy controls, before and after training with visual feedback. Results for this case study show differences in cortical information flow between the responding PD-with-FOG patient and the other two subject types, notably, an increased information flow in the beta range. Tentatively suggesting the formation of an alternative cortical sensory-motor pathway during training with visual feedback, these results are proposed as subject for further verification employing larger cohorts of patients