6,610 research outputs found

    Chinese Expert Consensus on Critical Care Ultrasound Applications at COVID-19 Pandemic

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    The spread of new coronavirus (SARS-Cov-2) follows a different pattern than previous respiratory viruses, posing a serious public health risk worldwide. World Health Organization (WHO) named the disease as COVID-19 and declared it a pandemic. COVID-19 is characterized by highly contagious nature, rapid transmission, swift clinical course, profound worldwide impact, and high mortality among critically ill patients. Chest X-ray, computerized tomography (CT), and ultrasound are commonly used imaging modalities. Among them, ultrasound, due to its portability and non-invasiveness, can be easily moved to the bedside for examination at any time. In addition, with use of 4G or 5G networks, remote ultrasound consultation can also be performed, which allows ultrasound to be used in isolated medial areas. Besides, the contact surface of ultrasound probe with patients is small and easy to be disinfected. Therefore, ultrasound has gotten lots of positive feedbacks from the frontline healthcare workers, and it has played an indispensable role in the course of COVID-19 diagnosis and follow up

    Atomic-level structural and chemical analysis of Cr-doped Bi2Se3 thin films

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    We present a study of the structure and chemical composition of the Cr-doped 3D topological insulator Bi2Se3. Single-crystalline thin films were grown by molecular beam epitaxy on Al2O3 (0001), and their structural and chemical properties determined on an atomic level by aberration-corrected scanning transmission electron microscopy and electron energy loss spectroscopy. A regular quintuple layer stacking of the Bi2Se3 film is found, with the exception of the first several atomic layers in the initial growth. The spectroscopy data gives direct evidence that Cr is preferentially substituting for Bi in the Bi2Se3 host. We also show that Cr has a tendency to segregate at internal grain boundaries of the Bi2Se3 film

    Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103

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    Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimerâ €™ s disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK 1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways

    Identification and classification of high risk groups for Coal Workers' Pneumoconiosis using an artificial neural network based on occupational histories: a retrospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>Coal workers' pneumoconiosis (CWP) is a preventable, but not fully curable occupational lung disease. More and more coal miners are likely to be at risk of developing CWP owing to an increase in coal production and utilization, especially in developing countries. Coal miners with different occupational categories and durations of dust exposure may be at different levels of risk for CWP. It is necessary to identify and classify different levels of risk for CWP in coal miners with different work histories. In this way, we can recommend different intervals for medical examinations according to different levels of risk for CWP. Our findings may provide a basis for further emending the measures of CWP prevention and control.</p> <p>Methods</p> <p>The study was performed using longitudinal retrospective data in the Tiefa Colliery in China. A three-layer artificial neural network with 6 input variables, 15 neurons in the hidden layer, and 1 output neuron was developed in conjunction with coal miners' occupational exposure data. Sensitivity and ROC analyses were adapted to explain the importance of input variables and the performance of the neural network. The occupational characteristics and the probability values predicted were used to categorize coal miners for their levels of risk for CWP.</p> <p>Results</p> <p>The sensitivity analysis showed that influence of the duration of dust exposure and occupational category on CWP was 65% and 67%, respectively. The area under the ROC in 3 sets was 0.981, 0.969, and 0.992. There were 7959 coal miners with a probability value < 0.001. The average duration of dust exposure was 15.35 years. The average duration of ex-dust exposure was 0.69 years. Of the coal miners, 79.27% worked in helping and mining. Most of the coal miners were born after 1950 and were first exposed to dust after 1970. One hundred forty-four coal miners had a probability value ≥0.1. The average durations of dust exposure and ex-dust exposure were 25.70 and 16.30 years, respectively. Most of the coal miners were born before 1950 and began to be exposed to dust before 1980. Of the coal miners, 90.28% worked in tunneling.</p> <p>Conclusion</p> <p>The duration of dust exposure and occupational category were the two most important factors for CWP. Coal miners at different levels of risk for CWP could be classified by the three-layer neural network analysis based on occupational history.</p

    The value of standards for health datasets in artificial intelligence-based applications

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    Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative)

    Eccentric Exercise Facilitates Mesenchymal Stem Cell Appearance in Skeletal Muscle

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    Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hematopoetic (CD45-) cells were evaluated in wild type (WT) and α7 integrin transgenic (α7Tg) mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1+CD45− stem cells were increased 2-fold in WT muscle post-exercise. The α7 integrin regulated the presence of Sca-1+ cells, with expansion occurring in α7Tg muscle and minimal cells present in muscle lacking the α7 integrin. Sca-1+CD45− cells isolated from α7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs), predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7+ cells and facilitated formation of eMHC+DiI− fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an α7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the α7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy

    Amygdala Atrophy and Its Functional Disconnection with the Cortico-Striatal-Pallidal-Thalamic Circuit in Major Depressive Disorder in Females

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    Background Major depressive disorder (MDD) is approximately twice as common in females than males. Furthermore, female patients with MDD tend to manifest comorbid anxiety. Few studies have explored the potential anatomical and functional brain changes associated with MDD in females. Therefore, the purpose of the present study was to investigate the anatomical and functional changes underlying MDD in females, especially within the context of comorbid anxiety. Methods In this study, we recruited antidepressant-free females with MDD (N = 35) and healthy female controls (HC; N = 23). The severity of depression and anxiety were evaluated by the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Structural and resting-state functional images were acquired on a Siemens 3.0 Tesla scanner. We compared the structural volumetric differences between patients and HC with voxel-based morphometry (VBM) analyses. Seed-based voxel-wise correlative analyses were used to identify abnormal functional connectivity. Regions with structural deficits showed a significant correlation between gray matter (GM) volume and clinical variables that were selected as seeds. Furthermore, voxel-wise functional connectivity analyses were applied to identify the abnormal connectivity relevant to seed in the MDD group. Results Decreased GM volume in patients was observed in the insula, putamen, amygdala, lingual gyrus, and cerebellum. The right amygdala was selected as a seed to perform connectivity analyses, since its GM volume exhibited a significant correlation with the clinical anxiety scores. We detected regions with disrupted connectivity relevant to seed primarily within the cortico-striatal-pallidal-thalamic circuit. Conclusions Amygdaloid atrophy, as well as decreased functional connectivity between the amygdala and the cortico-striatal-pallidal-thalamic circuit, appears to play a role in female MDD, especially in relation to comorbid anxiety

    De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

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    Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

    Acyl-Protein Thioesterase 2 Catalizes the Deacylation of Peripheral Membrane-Associated GAP-43

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    An acylation/deacylation cycle is necessary to maintain the steady-state subcellular distribution and biological activity of S-acylated peripheral proteins. Despite the progress that has been made in identifying and characterizing palmitoyltransferases (PATs), much less is known about the thioesterases involved in protein deacylation. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Using fluorescent fusion constructs, we measured in vivo the rate of deacylation of GAP-43 and its single acylated mutants in Chinese hamster ovary (CHO)-K1 and human HeLa cells. Biochemical and live cell imaging experiments demonstrated that single acylated mutants were completely deacylated with similar kinetic in both cell types. By RT-PCR we observed that acyl-protein thioesterase 1 (APT-1), the only bona fide thioesterase shown to mediate deacylation in vivo, is expressed in HeLa cells, but not in CHO-K1 cells. However, APT-1 overexpression neither increased the deacylation rate of single acylated GAP-43 nor affected the steady-state subcellular distribution of dually acylated GAP-43 both in CHO-K1 and HeLa cells, indicating that GAP-43 deacylation is not mediated by APT-1. Accordingly, we performed a bioinformatic search to identify putative candidates with acyl-protein thioesterase activity. Among several candidates, we found that APT-2 is expressed both in CHO-K1 and HeLa cells and its overexpression increased the deacylation rate of single acylated GAP-43 and affected the steady-state localization of diacylated GAP-43 and H-Ras. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution
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