Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

BACKGROUND: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT. METHODS: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch. RESULTS: Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P=0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P=0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P<0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion (Pall interaction<0.05). CONCLUSIONS: Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04487340.

Identification of a ZC3H12D-regulated competing endogenous RNA network for prognosis of lung adenocarcinoma at single-cell level.

BACKGROUND: To identify hub genes from the competing endogenous RNA (ceRNA) network of lung adenocarcinoma (LUAD) and to explore their potential functions on prognosis of patients from a single-cell perspective. METHODS: We performed RNA-sequencing of LUAD to construct ceRNA regulatory network, integrating with public databases to identify the vital pathways related to patients' prognosis and to reveal the expression level of hub genes under different conditions, the functional enrichment of co-expressed genes and their potential immune-related mechanisms. RESULTS: ZC3H12D-hsa-miR-4443-ENST00000630242 axis was found to be related with LUAD. Lower ZC3H12D expression was significantly associated with shorter overall survival (OS) of patients (HR = 2.007, P < 0.05), and its expression was higher in early-stage patients, including T1 (P < 0.05) and N0 (P < 0.05). Additionally, ZC3H12D expression was higher in immune cells displayed by single-cell RNA-sequencing data, especially in Treg cells of lung cancer and CD8 T cells, B cells and CD4 T cells of LUAD. The functional enrichment analysis showed that the co-expressed genes mainly played a role in lymphocyte activation and cytokine-cytokine receptor interaction. In addition, ZC3H12D was associated with multiple immune cells and immune molecules, including immune checkpoints CTLA4, CD96 and TIGIT. CONCLUSION: ZC3H12D-hsa-miR-4443-ENST00000630242 ceRNA network was identified in LUAD. ZC3H12D could affect prognosis of patients by regulating mRNA, miRNA, lncRNA, immune cells and immune molecules. Therefore, it may serve as a vital predictive marker and could be regarded as a potential therapeutic target for LUAD in the future.

An integrated analysis of the competing endogenous RNA network associated of prognosis of stage I lung adenocarcinoma.

BACKGROUND: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD). METHODS: Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07-2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001). CONCLUSIONS: This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.

CT-based radiomics for differentiating intracranial contrast extravasation from intraparenchymal haemorrhage after mechanical thrombectomy.

OBJECTIVE: To develop a nonenhanced CT-based radiomic signature for the differentiation of iodinated contrast extravasation from intraparenchymal haemorrhage (IPH) following mechanical thrombectomy. METHODS: Patients diagnosed with acute ischaemic stroke who underwent mechanical thrombectomy in 4 institutions from December 2017 to June 2020 were included in this retrospective study. The study population was divided into a training cohort and a validation cohort. The nonenhanced CT images taken after mechanical thrombectomy were used to extract radiomic features. The maximum relevance minimum redundancy (mRMR) algorithm was used to eliminate confounding variables. Afterwards, least absolute shrinkage and selection operator (LASSO) logistic regression was used to generate the radiomic signature. The diagnostic performance of the radiomic signature was evaluated by the area under the curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: A total of 166 intraparenchymal areas of hyperattenuation from 101 patients were used. The areas of hyperattenuation were randomly allocated to the training and validation cohorts at a ratio of 7:3. The AUC of the radiomic signature was 0.848 (95% confidence interval (CI) 0.780-0.917) in the training cohort and 0.826 (95% CI 0.705-0.948) in the validation cohort. The accuracy of the radiomic signature was 77.6%, with a sensitivity of 76.7%, a specificity of 78.9%, a PPV of 85.2%, and a NPV of 68.2% in the validation cohort. CONCLUSIONS: The radiomic signature constructed based on initial post-operative nonenhanced CT after mechanical thrombectomy can effectively differentiate IPH from iodinated contrast extravasation. KEY POINTS: • Radiomic features were extracted from intraparenchymal areas of hyperattenuation on initial post-operative CT scans after mechanical thrombectomy. • The nonenhanced CT-based radiomic signature can differentiate IPH from iodinated contrast extravasation early. • The radiomic signature may help prevent unnecessary rescanning after mechanical thrombectomy, especially in cases where contrast extravasation is highly suggestive.

Initial analysis of the middle problem in CT image reconstruction.

The interior and exterior problems have been extensively studied in the field of reconstruction of computed tomography (CT) images, which lead to important theoretical and practical results. In this study, we formulate a middle problem of CT image reconstruction, which is more challenging than either the interior or exterior problems. In the middle problem of CT image reconstruction, projection data are measured through and only through the middle dough-like region, so that each projection profile misses data not only internally but also on both sides. For an object with a radially symmetric exterior, we proved that the middle problem could be uniquely solved if the middle ring-shaped zone is piecewise constant or there is a known sub-region inside this middle region. Then, we designed and evaluated a POCS-based algorithm for middle tomography, which is to reconstruct a middle image only from the available data. Finally, the remaining issues are also discussed for further research.

Determining scientific impact using a collaboration index.

Researchers collaborate on scientific projects that are often measured by both the quantity and the quality of the resultant peer-reviewed publications. However, not all collaborators contribute to these publications equally, making metrics such as the total number of publications and the H-index insufficient measurements of individual scientific impact. To remedy this, we use an axiomatic approach to assign relative credits to the coauthors of a given paper, referred to as the A-index for its axiomatic foundation. In this paper, we use the A-index to compute the weighted sums of peer-reviewed publications and journal impact factors, denoted as the C- and P-indexes for collaboration and productivity, respectively. We perform an in-depth analysis of bibliometric data for 186 biomedical engineering faculty members and from extensive simulation. It is found that these axiomatically weighted indexes better capture a researcher's scientific caliber than do the total number of publications and the H-index, allowing for fairer and sharper evaluation of researchers with diverse collaborative behaviors.

A fast algorithm for high order total variation minimization based interior tomography.

Interior tomography as a promising X-ray imaging technique has received increasing attention in medical imaging field. In our previous works, we proposed a high-order total variation (HOT) minimization method for interior tomography and proved that the region of interest (ROI) can be reconstructed accurately by minimizing the HOT if the object image is piecewise polynomial within the ROI. In this paper, we propose a modified HOT (MHOT) and develop a fast MHOT minimization algorithm for interior tomography, based on split Bregman iteration and ordered-subset simultaneous algebraic reconstruction techniques (OS-SART). Numerical simulation demonstrates that our algorithm is computationally efficient and can be applied to obtain high-quality reconstructed image.

Data consistency condition for truncated projections in fan-beam geometry.

It is well known that CT projections are redundant. Over the past decades, significant efforts have been devoted to characterize the data redundancy in different aspects. Very recently, Clackdoyle and Desbat reported a new integral-type data consistency condition (DCC) for truncated 2D parallel-beam projections, which can be applied to a region inside a field of view (FOV) but outside of the convex hull of the compact support of an object. Inspired by their work, here we derive a more general condition for 2D fan-beam geometry with a general scanning trajectory. This extended DCC is verified with simulated projections of the Shepp-Logan phantom and a clinically collected sinogram. Then, we demonstrate an application of the proposed DCC.

[Stabilized thiomer PAA-Cys-6MNA].

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.

Enumeration and Molecular Characterization of Circulating Tumor Cell Using an Epithelial Cell Adhesion Molecule/Vimentin/Epidermal Growth Factor Receptor Joint Capture System in Lung Cancer.

Background: Detection rate and isolation yield of circulating tumor cells (CTCs) are low in lung cancer with approaches due to CTC invasiveness and heterogeneity. In this study, on the basis of the epithelial cell adhesion molecule (EpCAM) phenotype, markers of vimentin and epidermal growth factor receptor (EGFR) phenotype were added to jointly construct a precise and efficient CTC capture system for capture of lung cancer CTCs. Methods: A CTC capture system combined with EpCAM lipid magnetic bead (Ep-LMB)/vimentin lipid magnetic bead (Vi-LMB)/EGFR lipid magnetic bead (EG-LMB) was constructed, and its performance was tested. The amount of CTC captured in the blood of patients with lung cancer was detected by immunofluorescence identification and analyzed for clinical relevance. Results: The constructed CTC capture system has low cytotoxicity. The capture efficiency of lung cancer cells in phosphate belanced solution (PBS) system was 95.48%. The capture efficiency in the blood simulation system is 94.55%. The average number of CTCs in the blood of patients with lung cancer was 9.73/2 mL. The quantity distribution of CTCs is significantly correlated with tumor staging and metastasis. The area under the curve (AUC) of CTCs for the diagnosis of lung cancer was 0.9994 (95% CI = 0.9981-1.000, P < .0001). The cutoff value was 4.5/2 mL. The sensitivity was 99.39%, and the specificity was 96.88%. Conclusion: The EpCAM/vimentin/EGFR combined capture system has feasibility and high sensitivity in the detection of lung cancer CTC typing, which can be used as an auxiliary diagnostic indicator for lung cancer and is expected to promote the clinical application of CTCs.

LncRNA PRKCA-AS1 promotes LUAD progression and function as a ceRNA to regulate S100A16 by sponging miR-508-5p.

Objective: This study aimed to elucidate the underlying mechanism of LncRNA PRKCA-AS1 in lung adenocarcinoma (LUAD). Methods: The expression of LncRNA PRKCA-AS1, miR-508-5p and S100A16, in LUAD tissues or cell lines (NCI-H520 and H1299) was analyzed with qRT-PCR. The clinical diagnostic value of LncRNA PRKCAAS1, miR-508-5p and S100A16 in LUAD were analyzed by receptor operating characteristic (ROC) curve. Then we knockdown or overexpression of PRKCAAS1 in NCI-H520 and H1299 cells, and the cell function test was applied to detect the activity and metastasis level of cells in different transfection groups. Then Pearson correlation analysis was used for the correlation between miR-508-5p and PRKCA-AS1. The dual-luciferase reporter experiment and CHIRP analysis was conducted to verify the target binding relationship of PRKCA-AS1, miR-508-5p or S100A16. FISH assay analyzed the colocalization of PRKCA-AS1 and miR-508-5p in NCI-H520 and H1299 cells. Rescue experiment and tumorigenesis experiment in nude mice further explore the regulatory mechanisms of LncRNA PRKCA-AS1, miR-508-5p and S100A16 on LUAD progression in vitro and in vivo. Results: From the results, PRKCA-AS1 and S100A16 were up-regulated in LUAD tissues, while miR-508-5p was downregulated compared with the adjacent tissues. And gain-of-function revealed that PRKCA-AS1 knock-down apparently suppressed the cell proliferation and metastasis, whereas miR-508-5p inhibitors or S100A16 overexpression showed a opposite effect. In addition, there is evidence that PRKCA-AS1, miR-508-5p and S100A16 have a targeted regulatory relationship. Moreover, rescue experiment and tumorigenesis experiment in nude mice further confirmed that LncRNA PRKCA-AS1 regulates S100A16 through sponging miR-508-5p to regulate LUAD progression in vitro and in vivo. Conclusion: These results demonstrated that LncRNA PRKCA-AS1 might regulate LUAD by acting as a ceRNA via sponging miR-508-5p and regulating S100A16 expression, indicating that manipulation of PRKCA-AS1 might be a potential therapeutic strategy in LUAD.

Comprehensive analysis of prognostic value and immune infiltration of Regulator of Chromosome Condensation 2 in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) incidence and mortality take the leading place of most malignancies. Previous studies have revealed the regulator of chromosome condensation 1 (RCC1) family members played an essential role during tumorigenesis. However, its biological functions in LUAD still need further investigation. Methods: Several databases were applied to explore potential effects of RCC1 family members on LUAD, such as Oncomine, GEPIA, and cBioPortal. Real-time PCR and immunohistochemistry were used to verify the expression of RCC2 in stage I LUAD. H1975 and A549 were selected to explore the biological function of RCC2 in cellular malignant phenotype. Results: The expressions of RCC1 and RCC2 showed marked differences in malignant tissue compared to lung tissue. The higher the expression levels of RCC1 or RCC2 in LUAD patients, the shorter their overall survival (OS). In normal lung tissues, RCC1 expression was highly enriched in alveolar cells and endothelial cells. Compare with RCC1, RCC2 expression in normal lung tissue was significantly enriched in macrophages, B cells and granulocytes. Additionally, RCC2 expression level was correlated with multiple immune cell infiltration in LUAD. Moreover, the mutation or different sCNA status of RCC2 exerted influence on multiple immune cell infiltration distribution. We found that the upregulation of RCC1 and RCC2 were obviously related to TP53 mutation. GSEA analysis revealed that RCC2 was involved in the process of DNA replication, nucleotide excision repair and cell cycle, which might affect tumor progression through P53 signaling pathway. We further elucidated that downregulation of RCC2 could dramatically repress the migration and invasion of LUAD cells. Conclusions: The study demonstrated that RCC1 and RCC2 expression were markedly increased in early-stage of LUAD. Patients with high expression of RCC1 or RCC2 had a worse prognosis. Based on our analysis, RCC1 and RCC2 might exert influence on LUAD process through DNA replication, nucleotide excision repair and cell cycle, as well as cells migration and invasion. Different from RCC1, RCC2 also involved in immune infiltration. These analyses provided a novel insight into the identification of diagnostic biomarker.

PPAR-γ/NF-kB/AQP3 axis in M2 macrophage orchestrates lung adenocarcinoma progression by upregulating IL-6.

Aquaporin 3 (AQP3), which is mostly expressed in pulmonary epithelial cells, was linked to lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of AQP3 in the tumor microenvironment (TME) of LUAD have not been elucidated. Single-cell RNA sequencing (scRNA-seq) was used to study the composition, lineage, and functional states of TME-infiltrating immune cells and discover AQP3-expressing subpopulations in five LUAD patients. Then the identifications of its function on TME were examined in vitro and in vivo. AQP3 was associated with TNM stages and lymph node metastasis of LUAD patients. We classified inter- and intra-tumor diversity of LUAD into twelve subpopulations using scRNA-seq analyses. The analysis showed AQP3 was mainly enriched in subpopulations of M2 macrophages. Importantly, mechanistic investigations indicated that AQP3 promoted M2 macrophage polarization by the PPAR-γ/NF-κB axis, which affected tumor growth and migration via modulating IL-6 production. Mixed subcutaneous transplanted tumor mice and Aqp3 knockout mice models were further utilized, and revealed that AQP3 played a critical role in mediating M2 macrophage polarization, modulating glucose metabolism in tumors, and regulating both upstream and downstream pathways. Overall, our study demonstrated that AQP3 could regulate the proliferation, migration, and glycometabolism of tumor cells by modulating M2 macrophages polarization through the PPAR-γ/NF-κB axis and IL-6/IL-6R signaling pathway, providing new insight into the early detection and potential therapeutic target of LUAD.

Presence of Residual Cardiac Thrombus Predicts Poor Outcome in Cardioembolic Stroke After Reperfusion Therapy.

BACKGROUND: In patients with acute cardiogenic cerebral embolism, a residual thrombus may still be present in the cardiac cavity even after reperfusion therapy. We aimed to investigate the occurrence of a residual cardiac thrombus in cardioembolic stroke after reperfusion therapy and analyze its impact on clinical outcome. METHODS AND RESULTS: We enrolled patients with cardioembolic stroke from our prospectively collected database who underwent 2-phase cardiac computed tomography within 7 days after reperfusion therapy. Residual cardiac thrombus was defined as a filling defect on both early- and late-phase images, whereas circulatory stasis was defined as a filling defect only on the early-phase images in the left atrial appendage. The primary outcome was a poor clinical outcome (modified Rankin Scale score, 3-6) at 90 days. The secondary outcome was a composite end point event (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) at 90 days. A total of 303 patients were included, of whom 94 (31.0%) had a residual cardiac thrombus. Binary logistic regression analysis showed that the presence of a residual cardiac thrombus was associated with a poor clinical outcome (odds ratio, 1.951 [95% CI, 1.027-3.707]; P=0.041) but not circulatory stasis in the left atrial appendage (odds ratio, 1.096 [95% CI, 0.542-2.217]; P=0.798). Furthermore, there was no correlation between a residual cardiac thrombus and the composite end point event (30.0% versus 31.1%; P=1.000). CONCLUSIONS: Residual cardiac thrombus occurs in approximately one-third of patients with cardioembolic stroke after reperfusion therapy and is often indicative of a poor clinical outcome.

Mechanisms underlying the therapeutic effects of cinobufagin in treating melanoma based on network pharmacology, single-cell RNA sequencing data, molecular docking, and molecular dynamics simulation.

Malignant melanoma is one of the most aggressive of cancers; if not treated early, it can metastasize rapidly. Therefore, drug therapy plays an important role in the treatment of melanoma. Cinobufagin, an active ingredient derived from Venenum bufonis, can inhibit the growth and development of melanoma. However, the mechanism underlying its therapeutic effects is unclear. The purpose of this study was to predict the potential targets of cinobufagin in melanoma. We gathered known and predicted targets for cinobufagin from four online databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were then performed. Gene expression data were downloaded from the GSE46517 dataset, and differential gene expression analysis and weighted gene correlation network analysis were performed to identify melanoma-related genes. Using input melanoma-related genes and drug targets in the STRING online database and applying molecular complex detection (MCODE) analysis, we identified key targets that may be the potential targets of cinobufagin in melanoma. Moreover, we assessed the distribution of the pharmacological targets of cinobufagin in melanoma key clusters using single-cell data from the GSE215120 dataset obtained from the Gene Expression Omnibus database. The crucial targets of cinobufagin in melanoma were identified from the intersection of key clusters with melanoma-related genes and drug targets. Receiver operating characteristic curve (ROC) analysis, survival analysis, molecular docking, and molecular dynamics simulation were performed to gain further insights. Our findings suggest that cinobufagin may affect melanoma by arresting the cell cycle by inhibiting three protein tyrosine/serine kinases (EGFR, ERBB2, and CDK2). However, our conclusions are not supported by relevant experimental data and require further study.

miR-508-5p serves as an anti-oncogene by targeting S100A16 to regulate AKT signaling and epithelial-mesenchymal transition process in lung adenocarcinoma cells.

BACKGROUND: Our aim was to expose the effect of miR-508-5p on the developmental and biological behaviour of lung adenocarcinoma (LUAC). METHODS: The KM plotter was used to analyze the survival significance of miR-508-5p and S100A16 expression in LUAC patients. qRT-PCR was performed to detect the expression of miR-508-5p and S100A16 in LUAC tissue and LUAC cell lines. CCK8, colony formation and Transwell were performed to evaluate the effects of miR-508-5p and S100A16 on cell proliferation and metastasis. Dual luciferase reporter assay was used to verify that S100A16 were targets of miR-508-5p. Western blot analysis was performed to analyze protein expression. RESULTS: Results showed that low miR-508-5p expression in LUAC tissues indicated poorer overall survival of LUAC patients and miR-508-5p was downregulated in LUAC cell lines compared to the normal human lung epithelial cell line. miR-508-5p mimics could inhibit A549 cell proliferation and metastasis abilities, while miR-508-5p Antagomir showed the opposite effect. We identified S100A16 as one direct target of miR-508-5p, and rescuing S100A16 expression could reverse the effect of miR-508-5p mimics on A549 cell proliferation and metastasis. miR-508-5p could involve the coordination of AKT signaling and epithelial-mesenchymal transition (EMT) progress using western-blot assays and rescuing S100A16 expression could reverse the inhibited AKT signaling and EMT progress induced by miR-508-5p mimics. CONCLUSIONS: We found that miR-508-5p targeted S100A16 to regulate AKT signaling and EMT progress in A549 cells, resulting in impaired cell proliferation and metastasis activity, suggesting that miR-508-5p might be a promising therapeutic target and an important diagnostic and prognostic marker for improved LUAC therapeutic schedule.

Equilibrium Image Denoising with Implicit Differentiation.

Recent efforts on learning-based image denoising approaches use unrolled architectures with a fixed number of repeatedly stacked blocks. However, due to difficulties in training networks corresponding to deeper layers, simply stacking blocks may cause performance degradation, and the number of unrolled blocks needs to be manually tuned to find an appropriate value. To circumvent these problems, this paper describes an alternative approach with implicit models. To our best knowledge, our approach is the first attempt to model iterative image denoising through an implicit scheme. The model employs implicit differentiation to calculate gradients in the backward pass, thus avoiding the training difficulties of explicit models and elaborate selection of the iteration number. Our model is parameter-efficient and has only one implicit layer, which is a fixed-point equation that casts the desired noise feature as its solution. By simulating infinite iterations of the model, the final denoising result is given by the equilibrium that is achieved through accelerated black-box solvers. The implicit layer not only captures the non-local self-similarity prior for image denoising, but also facilitates training stability and thereby boosts the denoising performance. Extensive experiments show that our model leads to better performances than state-of-the-art explicit denoisers with enhanced qualitative and quantitative results.

Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours (HOPE): protocol for a randomised, controlled, multicentre study.

BACKGROUND: While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke (AIS) within 4.5 hours of symptom onset, there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic window. AIM: To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on CT perfusion at 4.5-24 hours after stroke onset (for stroke with unknown onset time, the midpoint of the time last known to be well and symptom recognition time; for wake-up stroke, the midpoint of the time last known to be well or sleep onset and wake up time) will benefit from intravenous thrombolysis. DESIGN: HOPE is a prospective, multicentre, randomised, open-label blinded endpoint trial with the stage of phase III. The treatment allocation employs 1:1 randomisation. The treatment arm under investigation is alteplase with standard therapy, the control arm is standard therapy. Eligibility imaging criteria include ischaemic core volume ≤70 mL, penumbra ≥10 mL and mismatch ≥20%. STUDY OUTCOMES: The primary outcome is non-disabled functional outcome (assessed as modified Rankin Scale score of 0-1 at 90 days). DISCUSSION: HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5-24 hours, which has the potential to extend time window and expand eligible population for thrombolysis therapy.

The anatomic study of clival screw fixation for the craniovertebral region.

PURPOSE: To study the anatomic parameters related to clival screw and establish reference data concerning the craniovertebral fixation technique. METHODS: Morphometric measurement of the clivus and the surrounding anatomic structures were obtained on 41 dry bone specimens. Then, 2-D CT reconstruction of the craniovertebral region of 30 patients (19 men and 11 women, ranging in age from 20-64 years with an average age of 38.8 years) were performed to measure the safety range for a 3.5-mm screw placement. Nine entry points were evaluated. Finally, one male fresh cadaver specimen (age 46 years) was dissected to observe the craniovertebral region. RESULTS: The clivus faces the basilar artery, the V ~ XII cranial nerves, the pons, and ventral medulla oblongata at its intracranial surface. The longitudinal diameter of extracranial clivus was 25.87 ± 2.64 mm. The narrowest diameter of the clivus was 12.84 ± 1.08 mm, the distance between the left and right hypoglossal canal was 32.70 ± 2.09 mm at its widest part. The distance between the left and right structures, the maximum value was 49.31 ± 4.16 mm at carotid canal, the minimum value was 16.54 ± 2.04 mm at the occipital condyle. The measurement of clival screws placement simulation via 2-D CT reconstruction images shows the maximum upper insertion angle of three components the optimal entry points, the candidate points, the limit entry points was 130.19°, 125.23° and 85.72°, and the total mean screw length was 7.57, 10.13 and 15.6 mm at the vertical entry angle, respectively. CONCLUSIONS: Clival screw placement is a viable option for craniovertebral fixation. There is a safe scope for the screw length and angle of the screw placement. And, these parameters obtained in the present study will be helpful for anyone contemplating the use of clival screw fixation.

High-order total variation minimization for interior SPECT.

Recently, we developed an approach for solving the computed tomography (CT) interior problem based on the high-order TV (HOT) minimization, assuming that a region-of-interest (ROI) is piecewise polynomial. In this paper, we generalize this finding from the CT field to the single-photon emission computed tomography (SPECT) field, and prove that if an ROI is piecewise polynomial, then the ROI can be uniquely reconstructed from the SPECT projection data associated with the ROI through the HOT minimization. Also, we propose a new formulation of HOT, which has an explicit formula for any n-order piecewise polynomial function, while the original formulation has no explicit formula for n ≥ 2. Finally, we verify our theoretical results in numerical simulation, and discuss relevant issues.