Whole-body center of gravity (CG) movements in relation to the center of pressure (COP) offer insights into the balance control strategies of the human body. Existing CG measurement methods using ...expensive measurement equipment fixed in a laboratory environment are not intended for continuous monitoring. The development of wireless sensing technology makes it possible to expand the measurement in daily life. The insole system is a wearable device that can evaluate human balance ability by measuring pressure distribution on the ground. In this study, a novel protocol (data preparation and model training) for estimating the 3-axis CG trajectory from vertical plantar pressures was proposed and its performance was evaluated. Input and target data were obtained through gait experiments conducted on 15 adult and 15 elderly males using a self-made insole prototype and optical motion capture system. One gait cycle was divided into four semantic phases. Features specified for each phase were extracted and the CG trajectory was predicted using a bi-directional long short-term memory (Bi-LSTM) network. The performance of the proposed CG prediction model was evaluated by a comparative study with four prediction models having no gait phase segmentation. The CG trajectory calculated with the optoelectronic system was used as a golden standard. The relative root mean square error of the proposed model on the 3-axis of anterior/posterior, medial/lateral, and proximal/distal showed the best prediction performance, with 2.12%, 12.97%, and 12.47%. Biomechanical analysis of two healthy male groups was conducted. A statistically significant difference between CG trajectories of the two groups was shown in the proposed model. Large CG sway of the medial/lateral axis trajectory and CG fall of the proximal/distal axis trajectory is shown in the old group. The protocol proposed in this study is a basic step to have gait analysis in daily life. It is expected to be utilized as a key element for clinical applications.
Purpose
The purpose of this study is to construct a synthetic dataset of ECG signal that overcomes the sensitivity of personal information and the complexity of disclosure policies.
Methods
The ...public dataset was constructed by generating synthetic data based on the deep learning model using a convolution neural network (CNN) and bi-directional long short-term memory (Bi-LSTM), and the effectiveness of the dataset was verified by developing classification models for ECG diagnoses.
Results
The synthetic 12-lead ECG dataset generated consists of a total of 6000 ECGs, with normal and 5 abnormal groups. The synthetic ECG signal has a waveform pattern similar to the original ECG signal, the average RMSE between the two signals is 0.042 µV, and the average cosine similarity is 0.993. In addition, five classification models were developed to verify the effect of the synthetic dataset and showed performance similar to that of the model made with the actual dataset. In particular, even when the real dataset was applied as a test set to the classification model trained with the synthetic dataset, the classification performance of all models showed high accuracy (average accuracy 93.41%).
Conclusion
The synthetic 12-lead ECG dataset was confirmed to perform similarly to the real-world 12-lead ECG in the classification model. This implies that a synthetic dataset can perform similarly to a real dataset in clinical research using AI. The synthetic dataset generation process in this study provides a way to overcome the medical data disclosure challenges constrained by privacy rights, a way to encourage open data policies, and contribute significantly to promoting cardiovascular disease research.
p53 is a frequent target for mutation in human tumors, and mutant p53 proteins can actively contribute to tumorigenesis. We employed a three-dimensional culture model in which nonmalignant breast ...epithelial cells form spheroids reminiscent of acinar structures found in vivo, whereas breast cancer cells display highly disorganized morphology. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the mevalonate pathway as significantly upregulated by mutant p53. Statins and sterol biosynthesis intermediates reveal that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with sterol gene promoters at least partly via SREBP transcription factors. Finally, p53 mutation correlates with highly expressed sterol biosynthesis genes in human breast tumors. These findings implicate the mevalonate pathway as a therapeutic target for tumors bearing mutations in p53.
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► Depletion of mutant p53 phenotypically reverts breast cancer cells in 3D culture ► Mutant p53 upregulates mevalonate pathway genes via SREBP transcription factors ► HMG-CoA reductase inhibitors mimic the phenotypic effects of mutant p53 depletion ► TP53 mutation correlates with elevation of mevalonate pathway genes in human tumors
Metastasis-associated p53 mutations disrupt breast tissue organization by upregulating transcription of sterol biosynthesis genes, highlighting p53 status as a predictive marker for responsiveness to statin therapy in cancer.
After a spinal cord injury, axons fail to regenerate in the adult mammalian central nervous system, leading to permanent deficits in sensory and motor functions. Increasing neuronal activity after an ...injury using electrical stimulation or rehabilitation can enhance neuronal plasticity and result in some degree of recovery; however, the underlying mechanisms remain poorly understood. We found that placing mice in an enriched environment before an injury enhanced the activity of proprioceptive dorsal root ganglion neurons, leading to a lasting increase in their regenerative potential. This effect was dependent on Creb-binding protein (Cbp)-mediated histone acetylation, which increased the expression of genes associated with the regenerative program. Intraperitoneal delivery of a small-molecule activator of Cbp at clinically relevant times promoted regeneration and sprouting of sensory and motor axons, as well as recovery of sensory and motor functions in both the mouse and rat model of spinal cord injury. Our findings showed that the increased regenerative capacity induced by enhancing neuronal activity is mediated by epigenetic reprogramming in rodent models of spinal cord injury. Understanding the mechanisms underlying activity-dependent neuronal plasticity led to the identification of potential molecular targets for improving recovery after spinal cord injury.
Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in ...humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like “hybrid neutrophils,” which originate from CD11b+CD15hiCD10−CD16low immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer.
•Lung tumors accumulate a subset of TANs with a granulocyte and APC hybrid phenotype•APC-like hybrid neutrophils are able to stimulate the anti-tumor T cell responses•IFN-γ and GM-CSF are requisite factors for the development of hybrid neutrophils•Ikaros negatively regulates the development of hybrid neutrophils from progenitors
Singhal et al. identify a subset of tumor-associated neutrophils (TANs) that can cross-present tumor antigens and activate anti-tumor T cells in stage I/II human lung cancer. The induction of these hybrid TANs from progenitors requires GM-CSF and IFN-γ and reduction of Ikaros.
Glucose metabolism in fish: a review Polakof, Sergio; Panserat, Stéphane; Soengas, José L. ...
Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology,
12/2012, Volume:
182, Issue:
8
Journal Article
Peer reviewed
Teleost fishes represent a highly diverse group consisting of more than 20,000 species living across all aquatic environments. This group has significant economical, societal and environmental ...impacts, yet research efforts have concentrated primarily on salmonid and cyprinid species. This review examines carbohydrate/glucose metabolism and its regulation in these model species including the role of hormones and diet. Over the past decade, molecular tools have been used to address some of the downstream components of these processes and these are incorporated to better understand the roles played by carbohydrates and their regulatory paths. Glucose metabolism remains a contentious area as many fish species are traditionally considered glucose intolerant and, therefore, one might expect that the use and storage of glucose would be considered of minor importance. However, the actual picture is not so clear since the apparent intolerance of fish to carbohydrates is not evident in herbivorous and omnivorous species and even in carnivorous species, glucose is important for specific tissues and/or for specific activities. Thus, our aim is to up-date carbohydrate metabolism in fish, placing it to the context of these new experimental tools and its relationship to dietary intake. Finally, we suggest that new research directions ultimately will lead to a better understanding of these processes.
In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of ...the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.
•Mandibular osteoradionecrosis developed in 5.5% of head and neck cancer patients.•Smoking at the time of RT and pre-RT tooth extraction were clinical risk factors.•The use of 3D-conformal RT vs ...intensity-modulated RT was an additional risk factor.•Modifiable risk factors should be minimized.
To evaluate the incidence of, and risk factors associated with, mandibular osteoradionecrosis (MORN) following radiation therapy (RT) for oral cavity and oropharyngeal cancers.
Patient and treatment records of 252 consecutive patients with oral cavity or oropharynx cancers treated with RT by a single radiation oncologist at a high volume academic institution from August 2009 to December 2015 were retrospectively reviewed. A Cox regression model was used to assess factors associated with the development of MORN. RT dosimetry was compared between patients with MORN and a matched cohort of patients without MORN.
MORN developed in 14 patients (5.5%), occurring 3–40 (median 8) months post-RT. Factors associated with MORN on univariable analysis included primary diagnosis of oral cavity vs oropharynx cancer (hazard ratio HR: 3.0, p=0.04), smoking at the time of RT (HR: 3.1, p=0.04), mandibular invasion of the primary (HR: 3.7, p=0.04), pre-RT tooth extraction (HR: 4.52, p=0.01), and treatment with 3D-conformal RT vs intensity-modulated RT (HR: 5.1, p=0.003). On multivariable analysis, pre-RT tooth extractions and RT technique remained significant. A dosimetric comparison between patients with and without MORN showed no significant differences.
The incidence of MORN is low in the modern era at a high volume academic center. Modifiable risk factors including pre-RT tooth extractions, smoking, and RT technique are associated with MORN, and the risk should be minimized with appropriate dental evaluation and treatment, smoking cessation efforts, and the use of intensity-modulated RT.
Global roll out of Xpert MTB/RIF technology has resulted in dramatic changes in TB diagnosis. However, benefits in resource-limited, high-burden TB/HIV settings, remain to be verified. In this paper ...we describe the characteristics of a large cohort of TB patients in a rural hospital in Southern Mozambique before and after Xpert MTB/RIF introduction, together with some determinants of favorable treatment outcome.
We conducted a retrospective cohort study of TB infected patients ≥15 years of age, diagnosed and treated at Carmelo Hospital of Chókwè between January 1, 2006 and December 31, 2017. Patient demographic and clinical characteristics, and treatment outcomes were recorded and compared before and after Xpert MTB/RIF, which was introduced in the second semester of 2012.
9,655 patients were analyzed, with 44.1% females. HIV testing was conducted in 99.9% of patients, with 82.8% having TB/HIV co-infection. 73.2% of patients had a favorable treatment outcome. No increase was observed in the number of TB patients identified after introduction of Xpert MTB/RIF testing.
Upon introduction, Xpert testing seemed to have a punctual beneficial effect on TB treatment outcomes, however this effect apparently disappeared shortly afterwards. Challenges remain for integration of TB and HIV care, as worse outcomes are reported for those patients diagnosed with TB shortly after starting ART, and also for those never starting ART. The need of reasonably excluding TB disease before ART start should be highlighted to every health care provider engaged in HIV care.
Aortic distensibility can be calculated using semi-automated methods to segment the aortic lumen on cine CMR (Cardiovascular Magnetic Resonance) images. However, these methods require visual quality ...control and manual localization of the region of interest (ROI) of ascending (AA) and proximal descending (PDA) aorta, which limit the analysis in large-scale population-based studies. Using 5100 scans from UK Biobank, this study sought to develop and validate a fully automated method to 1) detect and locate the ROIs of AA and PDA, and 2) provide a quality control mechanism.
The automated AA and PDA detection-localization algorithm followed these steps: 1) foreground segmentation; 2) detection of candidate ROIs by Circular Hough Transform (CHT); 3) spatial, histogram and shape feature extraction for candidate ROIs; 4) AA and PDA detection using Random Forest (RF); 5) quality control based on RF detection probability. To provide the ground truth, overall image quality (IQ = 0-3 from poor to good) and aortic locations were visually assessed by 13 observers. The automated algorithm was trained on 1200 scans and Dice Similarity Coefficient (DSC) was used to calculate the agreement between ground truth and automatically detected ROIs.
The automated algorithm was tested on 3900 scans. Detection accuracy was 99.4% for AA and 99.8% for PDA. Aorta localization showed excellent agreement with the ground truth, with DSC ≥ 0.9 in 94.8% of AA (DSC = 0.97 ± 0.04) and 99.5% of PDA cases (DSC = 0.98 ± 0.03). AA×PDA detection probabilities could discriminate scans with IQ ≥ 1 from those severely corrupted by artefacts (AUC = 90.6%). If scans with detection probability < 0.75 were excluded (350 scans), the algorithm was able to correctly detect and localize AA and PDA in all the remaining 3550 scans (100% accuracy).
The proposed method for automated AA and PDA localization was extremely accurate and the automatically derived detection probabilities provided a robust mechanism to detect low quality scans for further human review. Applying the proposed localization and quality control techniques promises at least a ten-fold reduction in human involvement without sacrificing any accuracy.
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