Purpose:
The streak artifacts caused by metal implants have long been recognized as a problem that limits various applications of CT imaging. In this work, the authors propose an iterative metal ...artifact reduction algorithm based on constrained optimization.
Methods:
After the shape and location of metal objects in the image domain is determined automatically by the binary metal identification algorithm and the segmentation of “metal shadows” in projection domain is done, constrained optimization is used for image reconstruction. It minimizes a predefined function that reflectsa priori knowledge of the image, subject to the constraint that the estimated projection data are within a specified tolerance of the available metal-shadow-excluded projection data, with image non-negativity enforced. The minimization problem is solved through the alternation of projection-onto-convex-sets and the steepest gradient descent of the objective function. The constrained optimization algorithm is evaluated with a penalized smoothness objective.
Results:
The study shows that the proposed method is capable of significantly reducing metal artifacts, suppressing noise, and improving soft-tissue visibility. It outperforms the FBP-type methods and ART and EM methods and yields artifacts-free images.
Conclusions:
Constrained optimization is an effective way to deal with CT reconstruction with embedded metal objects. Although the method is presented in the context of metal artifacts, it is applicable to general “missing data” image reconstruction problems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To investigate the effect of simvastatin on the immunoreaction and inflammation in rats with asthma through the NOTCH signaling pathway, a total of 36 Sprague-Dawley (SD) rats were enrolled and ...randomly divided into the normal group (n=12), model group (n=12) and simvastatin group (n=12). The rats in the normal group were fed normally, those in the model group were prepared into models of asthma, and those in the simvastatin group were prepared into models of asthma and intervened with simvastatin. Next, the morphology of airway tissues was observed via hematoxylin-eosin (HE) staining assay. Besides, immunohistochemistry was employed to determine the expression of interferon-γ (INF-γ), and the relative protein expression levels of NOTCH2 and NOTCH3 were measured by Western blotting (WB). Additionally, enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR) assay were carried out to detect the content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and the relative mRNA expression levels of INF-γ, IL-6 and TNF-α, respectively. HE staining results uncovered that the airway tissues displayed normal morphology in the normal group and disordered morphology and obvious inflammatory infiltration in the model group. In comparison with the model group, the simvastatin group exhibited significantly improved morphology of airway tissues. Based on immunohistochemistry, the average optical density of INF-γ positive expression was increased in the model group and simvastatin group compared with that in the normal group (P<0.05), and it was distinctly lower in the simvastatin group than that in the model group (P<0.05). The results of WB showed that compared with those in the normal group, the relative protein expression levels of NOTCH2 and NOTCH3 were elevated in model group and simvastatin group (P<0.05), whereas they were overtly reduced in simvastatin group compared with those in model group (P<0.05). It was found through ELISA that the model group and simvastatin group had raised content of IL-6 and TNF-α in comparison with the normal group (P<0.05), while the simvastatin group exhibited markedly decreased content of IL-6 and TNF-α in comparison with the model group (P<0.05). The results of qPCR revealed that the relative mRNA expression levels of INF-γ, IL-6 and TNF-α were distinctly up-regulated in the model group and simvastatin group compared with those in the normal group, displaying statistically significant differences (P<0.05), whereas they were markedly lowered in simvastatin group compared with those in the model group, showing statistically significant differences (P<0.05). Simvastatin represses the immunoreaction and inflammation in rats with asthma by down-regulating the NOTCH signaling pathway.
Cognitive decline occurs frequently in Parkinson's disease (PD), which greatly decreases the quality of life of patients. However, the mechanisms remain to be investigated. Neuroinflammation mediated ...by overactivated microglia is a common pathological feature in multiple neurological disorders, including PD. This study is designed to explore the role of microglia in cognitive deficits by using a rotenone-induced mouse PD model.
To evaluate the role of microglia in rotenone-induced cognitive deficits, PLX3397, an inhibitor of colony-stimulating factor 1 receptor, and minocycline, a widely used antibiotic, were used to deplete or inactivate microglia, respectively. Cognitive performance of mice among groups was detected by Morris water maze, objective recognition, and passive avoidance tests. Neurodegeneration, synaptic loss, α-synuclein phosphorylation, glial activation, and apoptosis were determined by immunohistochemistry and Western blot or immunofluorescence staining. The gene expression of inflammatory factors and lipid peroxidation were further explored by using RT-PCR and ELISA kits, respectively.
Rotenone dose-dependently induced cognitive deficits in mice by showing decreased performance of rotenone-treated mice in the novel objective recognition, passive avoidance, and Morris water maze compared with that of vehicle controls. Rotenone-induced cognitive decline was associated with neurodegeneration, synaptic loss, and Ser129-phosphorylation of α-synuclein and microglial activation in the hippocampal and cortical regions of mice. A time course experiment revealed that rotenone-induced microglial activation preceded neurodegeneration. Interestingly, microglial depletion by PLX3397 or inactivation by minocycline significantly reduced neuronal damage and α-synuclein pathology as well as improved cognitive performance in rotenone-injected mice. Mechanistically, PLX3397 and minocycline attenuated rotenone-induced astroglial activation and production of cytotoxic factors in mice. Reduced lipid peroxidation was also observed in mice treated with combined PLX3397 or minocycline and rotenonee compared with rotenone alone group. Finally, microglial depletion or inactivation was found to mitigate rotenone-induced neuronal apoptosis.
Taken together, our findings suggested that microglial activation contributes to cognitive impairments in a rotenone-induced mouse PD model via neuroinflammation, oxidative stress, and apoptosis, providing novel insight into the immunopathogensis of cognitive deficits in PD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
An increasing number of COVID‐19 patients worldwide will probably need tracheostomy in an emergency or at the recovering stage of COVID‐19. We explored the safe and effective management of ...tracheostomy in COVID‐19 patients, to benefit patients and protect health care workers at the same time.
Methods
We retrospectively analyzed 11 hospitalized COVID‐19 patients undergoing tracheostomy. Clinical features of patients, ventilator withdrawal after tracheostomy, surgical complications, and nosocomial infection of the health care workers associated with the tracheostomy were analyzed.
Results
The tracheostomy of all the 11 cases (100%) was performed successfully, including percutaneous tracheostomy of 6 cases (54.5%) and conventional open tracheostomy of 5 cases (45.5%). No severe postoperative complications occurred, and no health care workers associated with the tracheostomy are confirmed to be infected by SARS‐CoV‐2.
Conclusion
Comprehensive evaluation before tracheostomy, optimized procedures during tracheostomy, and special care after tracheostomy can make the tracheostomy safe and beneficial in COVID‐19 patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Clustering analysis is widely used to interpret biomedical data and uncover new knowledge and patterns. However, conventional clustering methods are not effective when dealing with sparse biomedical ...data. To overcome this limitation, we propose a hierarchical clustering method called polynomial weight-adjusted sparse clustering (PWSC).
The PWSC algorithm adjusts feature weights using a polynomial function, redefines the distances between samples, and performs hierarchical clustering analysis based on these adjusted distances. Additionally, we incorporate a consensus clustering approach to determine the optimal number of classifications. This consensus approach utilizes relative change in the cumulative distribution function to identify the best number of clusters, resulting in more stable clustering results. Leveraging the PWSC algorithm, we successfully classified a cohort of gastric cancer patients, enabling categorization of patients carrying different types of altered genes. Further evaluation using Entropy showed a significant improvement (p = 2.905e-05), while using the Calinski-Harabasz index demonstrates a remarkable 100% improvement in the quality of the best classification compared to conventional algorithms. Similarly, significantly increased entropy (p = 0.0336) and comparable CHI, were observed when classifying another colorectal cancer cohort with microbial abundance. The above attempts in cancer subtyping demonstrate that PWSC is highly applicable to different types of biomedical data. To facilitate its application, we have developed a user-friendly tool that implements the PWSC algorithm, which canbe accessed at http://pwsc.aiyimed.com/ .
PWSC addresses the limitations of conventional approaches when clustering sparse biomedical data. By adjusting feature weights and employing consensus clustering, we achieve improved clustering results compared to conventional methods. The PWSC algorithm provides a valuable tool for researchers in the field, enabling more accurate and stable clustering analysis. Its application can enhance our understanding of complex biological systems and contribute to advancements in various biomedical disciplines.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The DNA damage and repair pathway is considered a promising target for developing strategies against cancer. RAD51, also known as RECA, is a recombinase that performs the critical step in homologous ...recombination. RAD51 has recently received considerable attention due to its function in tumor progression and its decisive role in tumor resistance to chemotherapy. However, its role in pancreatic cancer has seldom been investigated. In this report, we provide evidence that RAD51, regulated by KRAS, promotes pancreatic cancer cell proliferation. Furthermore, RAD51 regulated aerobic glycolysis by targeting hypoxia inducible factor 1α (HIF1α).
TCGA (The Cancer Genome Atlas) dataset analysis was used to examine the impact of RAD51 expression on overall survival of pancreatic cancer patients. Lentivirus-mediated transduction was used to silence RAD51 and KRAS expression. Quantitative real-time PCR and western blot analysis validated the efficacy of the knockdown effect. Analysis of the glycolysis process in pancreatic cancer cells was also performed. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay.
Pancreatic cancer patients with higher levels of RAD51 exhibited worse survival. In pancreatic cancer cells, RAD51 positively regulated cell proliferation, decreased intracellular reactive oxygen species (ROS) production and increased the HIF1α protein level. KRAS/MEK/ERK activation increased RAD51 expression. In addition, RAD51 was a positive regulator of aerobic glycolysis.
The present study reveals novel roles for RAD51 in pancreatic cancer that are associated with overall survival prediction, possibly through a mechanism involving regulation of aerobic glycolysis. These findings may provide new predictive and treatment targets for pancreatic cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Serine alleviates inflammatory responses and is beneficial for gut health; however, whether it exerts any effects on ulcerative colitis or regulates intestinal microbiota remains unknown. We ...investigated the effects of serine supplementation on colonic morphology, inflammation, and microbiota composition in dextran sulfate sodium (DSS)-induced colitis model in mice. Acute colitis was induced through the oral intake of 3.5% DSS in water for 7 days. Mice with acute colitis were divided into two groups; The DSS and Ser-treated groups were rectally administrated with PBS or 1% (w/v) serine (40 mg/kg body weight) for 7 days. The results showed that serine decreased the disease activity index, as well as myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine concentrations in colonic tissue, while serine improved colonic morphology and inhibited cell apoptosis in colitis mice. In addition, 16S rRNA phylogenetic sequencing revealed a shift in bacterial community composition, and changes in microbiota functional profiles following serine supplementation, although no significant difference in α-diversity analysis was observed. The effects of serine supplementation helped on the recovery of major perturbations to macrobiotic functions, such as amino acids metabolism; tissue replication and repair; and cell growth and death. Serine might have great potential for the renewal of colonic tissue in DSS-induced colitis.
Amanita poisoning is one of the most deadly types of mushroom poisoning. α-Amanitin is the main lethal toxin in amanita, and the human-lethal dose is about 0.1 mg/kg. Most of the commonly used ...detection techniques for α-amanitin require expensive instruments. In this study, the α-amanitin aptamer was selected as the research object, and the stem-loop structure of the original aptamer was not damaged by truncating the redundant bases, in order to improve the affinity and specificity of the aptamer. The specificity and affinity of the truncated aptamers were determined using isothermal titration calorimetry (ITC) and gold nanoparticles (AuNPs), and the affinity and specificity of the aptamers decreased after truncation. Therefore, the original aptamer was selected to establish a simple and specific magnetic bead-based enzyme linked immunoassay (MELISA) method for α-amanitin. The detection limit was 0.369 μg/mL, while, in mushroom it was 0.372 μg/mL and in urine 0.337 μg/mL. Recovery studies were performed by spiking urine and mushroom samples with α-amanitin, and these confirmed the desirable accuracy and practical applicability of our method. The α-amanitin and aptamer recognition sites and binding pockets were investigated in an in vitro molecular docking environment, and the main binding bases of both were T3, G4, C5, T6, T7, C67, and A68. This study truncated the α-amanitin aptamer and proposes a method of detecting α-amanitin.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Seed germination is crucial for the life cycle of plants and maximum crop production. This critical developmental step is regulated by diverse endogenous hormones, reactive oxygen species (ROS) and ...exogenous (light, temperature) factors. Reactive oxygen species promote the release of seed dormancy by biomolecules oxidation, testa weakening and endosperm decay. Reactive oxygen species modulate metabolic and hormone signaling pathways that induce and maintain seed dormancy and germination. Endosperm provides nutrients and senses environmental signals to regulate the growth of the embryo by secreting timely signals. The growing energy demand of the developing embryo and endosperm is fulfilled by functional mitochondria. Mitochondrial matrix-localized heat shock protein GhHSP24.7 controls seed germination in a temperature-dependent manner. In this review, we summarize comprehensive view of biochemical and molecular mechanisms, which coordinately control seed germination. We also discuss that the accurate and optimized coordination of ROS, mitochondria, heat shock proteins is required to permit testa rupture and subsequent germination.
Melanoma is a deadly form of skin cancer that accounts for a disproportionally large proportion of cancer-related deaths in younger people. Compared with most other skin cancers, a feature of ...melanoma is its high metastatic capacity, although the mechanisms that confer this are not well understood. The Hippo pathway is a key regulator of organ growth and cell fate that is deregulated in many cancers. To analyse the Hippo pathway in cutaneous melanoma, we generated a transcriptional signature of melanoma cells that overexpressed YAP, the key downstream Hippo pathway oncoprotein. YAP-mediated transcriptional activity varied in melanoma cell lines but did not cluster with known genetic drivers of melanomagenesis such as BRAF and NRAS mutations. Instead, it correlated strongly with published gene expression profiles linked to melanoma cell invasiveness and varied throughout the metastatic cascade in melanoma patient tumours. Consistent with this, YAP was both necessary and sufficient for melanoma cell invasion in vitro. In vivo, YAP promoted spontaneous melanoma metastasis, whilst the growth of YAP-expressing primary tumours was impeded. Finally, we identified the YAP target genes AXL, THBS1 and CYR61 as key mediators of YAP-induced melanoma cell invasion. These data suggest that YAP is a critical regulator of melanoma metastasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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