Identification and verification of AK4 as a protective immune-related biomarker in adipose-derived stem cells and breast cancer.

Background: Breast cancer (BC) remains the most common cancer among women, and novel post-surgical reconstruction techniques, including autologous fat transplantation, have emerged. While Adipose-derived stem cells (ADSCs) are known to impact the viability of fat grafts, their influence on breast cancer progression remains unclear. This study aims to elucidate the genetic interplay between ADSCs and breast cancer, focusing on potential therapeutic targets. Methods: Using the GEO and TCGA databases, we pinpointed differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and pseudogenes of ADSCs and BC. We performed functional enrichment analysis and constructed protein-protein interaction (PPI), RNA binding protein (RBP)-pseudogene-mRNA, and lncRNA-miRNA-transcription factor (TF)-gene networks. Our study delved into the correlation of AK4 expression with 33 different malignancies and examined its impact on prognostic outcomes across a pan-cancer cohort. Additionally, we scrutinized immune infiltration, microsatellite instability, and tumor mutational burden, and conducted single-cell analysis to further understand the implications of AK4 expression. We identified novel sample subtypes based on hub genes using the ConsensusClusterPlus package and examined their association with immune infiltration. The random forest algorithm was used to screen DE mRNAs between subtypes to validate the powerful prognostic prediction ability of the artificial neural network. Results: Our analysis identified 395 DE mRNAs, 3 DE miRNAs, 84 DE lncRNAs, and 26 DE pseudogenes associated with ADSCs and BC. Of these, 173 mRNAs were commonly regulated in both ADSCs and breast cancer, and 222 exhibited differential regulation. The PPI, RBP-pseudogene-mRNA, and lncRNA-miRNA-TF-gene networks suggested AK4 as a key regulator. Our findings support AK4 as a promising immune-related therapeutic target for a wide range of malignancies. We identified 14 characteristic genes based on the AK4-related cluster using the random forest algorithm. Our artificial neural network yielded excellent diagnostic performance in the testing cohort with AUC values of 0.994, 0.973, and 0.995, indicating its ability to distinguish between breast cancer and non-breast cancer cases. Conclusions: Our research sheds light on the dual role of ADSCs in BC at the genetic level and identifies AK4 as a key protective mRNA in breast cancer. We found that AK4 significantly predicts cancer prognosis and immunotherapy, indicating its potential as a therapeutic target.

Trajectory of gestational weight gain is related to birthweight: The TAWS cohort study in China.

Few studies have reported the timing and amount of gestational weight gain (GWG) to prevent large-for-gestational-age (LGA) or small-for-gestational-age (SGA). This study aimed to evaluate the association of GWG velocity in each trimester with LGA or SGA based on data from the Taicang and Wuqiang cohort study (TAWS, n = 2008). We used a linear mixed model to evaluate the association of trimester-specific GWG velocity with birthweight categories and stratified by prepregnancy body mass index category and parity. For normal-weight pregnant women, mothers with LGA births had higher GWG velocities than mothers with appropriate-for-gestational-age (AGA) births in the first trimester (0.108 vs. 0.031 kg/week, p < 0.01), second trimester (0.755 vs. 0.631 kg/week, p < 0.01) and third trimester (0.664 vs. 0.594 kg/week, p < 0.01); in contrast, mothers with SGA births had lower GWG velocities than mothers with AGA births in the second trimester (0.528 vs. 0.631 kg/week, p < 0.01) and third trimester (0.541 vs. 0.594 kg/week, p < 0.01). For normal-weight pregnant women with AGA births, multiparous women had lower GWG velocities than primiparous women in the second (0.602 vs. 0.643 kg/week, p < 0.01) and third trimesters (0.553 vs. 0.606 kg/week, p < 0.01). Therefore, for normal-weight women, LGA prevention would begin in early pregnancy and continue until delivery and the second and third trimesters may be critical periods for preventing SGA; in addition, among normal-weight pregnant women with AGA births, multiparous women tend to have lower weight gain velocities than primiparous women.

Segmentation method of magnetic resonance imaging brain tumor images based on improved UNet network.

Background: Glioma is a primary malignant craniocerebral tumor commonly found in the central nervous system. According to research, preoperative diagnosis of glioma and a full understanding of its imaging features are very significant. Still, the traditional segmentation methods of image dispensation and machine wisdom are not acceptable in glioma segmentation. This analysis explores the potential of magnetic resonance imaging (MRI) brain tumor images as an effective segmentation method of glioma. Methods: This study used 200 MRI images from the affiliated hospital and applied the 2-dimensional residual block UNet (2DResUNet). Features were extracted from input images using a 2×2 kernel size (64-kernel) 1-step 2D convolution (Conv) layer. The 2DDenseUNet model implemented in this study incorporates a ResBlock mechanism within the UNet architecture, as well as a Gaussian noise layer for data augmentation at the input stage, and a pooling layer for replacing the conventional 2D convolutional layers. Finally, the performance of the proposed protocol and its effective measures in glioma segmentation were verified. Results: The outcomes of the 5-fold cross-validation evaluation show that the proposed 2DResUNet and 2DDenseUNet structure has a high sensitivity despite the slightly lower evaluation result on the Dice score. At the same time, compared with other models used in the experiment, the DM-DA-UNet model proposed in this paper was significantly improved in various indicators, increasing the reliability of the model and providing a reference and basis for the accurate formulation of clinical treatment strategies. The method used in this study showed stronger feature extraction ability than the UNet model. In addition, our findings demonstrated that using generalized die harm and prejudiced cross entropy as loss functions in the training process effectively alleviated the class imbalance of glioma data and effectively segmented glioma. Conclusions: The method based on the improved UNet network has obvious advantages in the MRI brain tumor portrait segmentation procedure. The result showed that we developed a 2D residual block UNet, which can improve the incorporation of glioma segmentation into the clinical process.

[Prevalence of and risk factors for perceived absence of breast milk supply in Chinese lactating women in 2013].

OBJECTIVE: To investigate the prevalence and influencing factors of postpartum perceived absence of breast milk supply among Chinese mothers in 2013. METHODS: This is a cross-sectional study based on the data collected from children and mothers under 2 years of age in 2013 as part of the nutrition and health surveillance of Chinese residents. In this study, multistage stratified cluster sampling method was used to select subjects from 55 countires/districts in 30 provinces in China. The perceived absence of breast milk supply was defined as the mother's self-reported absence of breast milk and failure to breastfeed. Breastfeeding knowledge, maternal breastfeeding knowledge and general characteristics were collected through a structured questionnaire. Univariate analysis and Logistic regression were used to analyze the factors associated with perceived absence of breast milk supply. RESULTS: A total of 12091 mothers were included in the study, including 419 in the perceived non-breastfeeding group, the prevalence of perceived absence of breast milk supply was 3.5%. Multivariate Logistic regression showed maternal age(OR=1.04, 95%CI 1.02-1.06), postpartum hemorrhage(OR=2.03, 95%CI 1.30-3.16), and belief that breastfeeding should continue beyond 12 months of age(OR=0.27, 95%CI 0.17-0.45), not knowing how to breastfeed(OR=3.31, 95%CI: 2.31-4.74) were the main influencing factors for perceived absence of breast milk supply after delivery. CONCLUSION: Age, postpartum hemorrhage and knowledge level of breastfeeding are the main risk factors for perceived absence of breast milk supply, and knowledge level of breastfeeding is a modifiable factor.

Hippuric acid alleviates dextran sulfate sodium-induced colitis via suppressing inflammatory activity and modulating gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with metabolic disorder and gut dysbiosis. Decreased abundance of hippuric acid (HA) was found in patients with IBD. HA, metabolized directly from benzoic acid in the intestine and indirectly from polyphenols, serves as a marker of polyphenol catabolism. While polyphenols and benzoic acid have been shown to alleviate intestinal inflammation, the role of HA in this context remains unknown. Herein, we investigated the effects and mechanism of HA on DSS-induced colitis mice. The results revealed that HA alleviated clinical activity and intestinal barrier damage, decreased pro-inflammatory cytokine production. Metagenomic sequencing suggested that HA treatment restored the gut microbiota, including an increase in beneficial gut bacteria such as Adlercreutzia, Eubacterium, Schaedlerella and Bifidobacterium_pseudolongum. Furthermore, we identified 113 candidate genes associated with IBD that are potentially under HA regulation through network pharmacological analyses. 10 hub genes including ALB, IL-6, HSP90AA1, and others were identified using PPI analysis and validated using molecular docking and mRNA expression analysis. Additionally, KEGG analysis suggested that the renin-angiotensin system (RAS), NF-κB signaling and Rap1 signaling pathways were important pathways in the response of HA to colitis. Thus, HA may provide novel biotherapy options for IBD.

Dose-Incorporated Deep Ensemble Learning for Improving Brain Metastasis SRS Outcome Prediction.

PURPOSE/OBJECTIVE(S): To develop a novel deep ensemble learning model for accurate prediction of brain metastasis(BM) local control outcomes following stereotactic radiosurgery(SRS). MATERIALS/METHODS: A total of 114 BMs from 82 patients were evaluated, including 26 BMs that developed biopsy-confirmed local failure post-SRS. The SRS spatial dose distribution(Dmap) of each BM was registered to the planning contrast-enhanced T1(T1-CE) MR. Axial slices of the Dmap, T1-CE, and PTV segmentation(PTVseg) intersecting the BM center were extracted within a fixed field-of-view determined by the V60% in Dmap. A spherical projection was implemented to transform planar image content onto a spherical surface using multiple projection centers, and the resultant T1-CE/Dmap/PTVseg projections were stacked as a 3-channel variable. Four VGG-19 deep encoders were utilized in an ensemble design, with each sub-model using a different spherical projection formula as input for BM outcome prediction. In each sub-model, clinical features after positional encoding were fused with VGG-19 deep features to generate logit results. The ensemble's outcome was synthesized from the four sub-model results via logistic regression. A total of 10 model versions with random validation sample assignments were trained to study model robustness. Performance was compared to 1) a single VGG-19 encoder; 2) an ensemble with T1-CE MRI as the sole image input after projections; and 3) an ensemble with the same image input design without clinical feature inclusion. RESULTS: The ensemble model achieved an excellent AUCROC=0.89±0.02 with high sensitivity(0.82±0.05), specificity(0.84±0.11), and accuracy(0.84±0.08) results. This outperformed the MRI-only VGG-19 encoder (sensitivity:0.35±0.01, AUC:0.64±0.08), the MRI-only deep ensemble (sensitivity:0.60±0.09, AUC:0.68±0.06), and the 3-channel ensemble without clinical feature fusion (sensitivity:0.78±0.08, AUC:0.84±0.03). CONCLUSION: Facilitated by the spherical image projection method, a deep ensemble model incorporating Dmap and clinical variables demonstrated an excellent performance in predicting BM post-SRS local failure. Our novel approach could improve other radiotherapy outcome models and warrants further evaluation.

Integrating multi-omics data reveals energy and stress signaling activated by abscisic acid in Arabidopsis.

Phytohormones are essential signaling molecules regulating various processes in growth, development, and stress responses. Genetic and molecular studies, especially using Arabidopsis thaliana (Arabidopsis), have discovered many important players involved in hormone perception, signal transduction, transport, and metabolism. Phytohormone signaling pathways are extensively interconnected with other endogenous and environmental stimuli. However, our knowledge of the huge and complex molecular network governed by a hormone remains limited. Here we report a global overview of downstream events of an abscisic acid (ABA) receptor, REGULATORY COMPONENTS OF ABA RECEPTOR (RCAR) 6 (also known as PYRABACTIN RESISTANCE 1 [PYR1]-LIKE [PYL] 12), by integrating phosphoproteomic, proteomic and metabolite profiles. Our data suggest that the RCAR6 overexpression constitutively decreases the protein levels of its coreceptors, namely clade A protein phosphatases of type 2C, and activates sucrose non-fermenting-1 (SNF1)-related protein kinase 1 (SnRK1) and SnRK2, the central regulators of energy and ABA signaling pathways. Furthermore, several enzymes in sugar metabolism were differentially phosphorylated and expressed in the RCAR6 line, and the metabolite profile revealed altered accumulations of several organic acids and amino acids. These results indicate that energy- and water-saving mechanisms mediated by the SnRK1 and SnRK2 kinases, respectively, are under the control of the ABA receptor-coreceptor complexes.

PeNAC67-PeKAN2-PeSCL23 and B-class MADS-box transcription factors synergistically regulate the specialization process from petal to lip in Phalaenopsis equestris.

The molecular basis of orchid flower development involves a specific regulatory program in which MADS-box transcription factors play a central role. The recent 'perianth code' model hypothesizes that two types of higher-order heterotetrameric complexes, namely SP complex and L complex, play pivotal roles in the orchid perianth organ formation. Therefore, we explored their roles and searched for other components of the regulatory network.Through the combined analysis for transposase-accessible chromatin with high-throughput sequencing and RNA sequencing of the lip-like petal and lip from Phalaenopsis equestris var.trilip, transcription factor-(TF) genes involved in lip development were revealed. PeNAC67 encoding a NAC-type TF and PeSCL23 encoding a GRAS-type TF were differentially expressed between the lip-like petal and the lip. PeNAC67 interacted with and stabilized PeMADS3, which positively regulated the development of lip-like petal to lip. PeSCL23 and PeNAC67 competitively bound with PeKAN2 and positively regulated the development of lip-like petal to petal by affecting the level of PeMADS3. PeKAN2 as an important TF that interacts with PeMADS3 and PeMADS9 can promote lip development. These results extend the 'perianth code' model and shed light on the complex regulation of orchid flower development.

KLF5 regulates actin remodeling to enhance the metastasis of nasopharyngeal carcinoma.

Transcription factors (TFs) engage in various cellular essential processes including differentiation, growth and migration. However, the master TF involved in distant metastasis of nasopharyngeal carcinoma (NPC) remains largely unclear. Here we show that KLF5 regulates actin remodeling to enhance NPC metastasis. We analyzed the msVIPER algorithm-generated transcriptional regulatory networks and identified KLF5 as a master TF of metastatic NPC linked to poor clinical outcomes. KLF5 regulates actin remodeling and lamellipodia formation to promote the metastasis of NPC cells in vitro and in vivo. Mechanistically, KLF5 preferentially occupies distal enhancer regions of ACTN4 to activate its transcription, whereby decoding the informative DNA sequences. ACTN4, extensively localized within actin cytoskeleton, facilitates dense and branched actin networks and lamellipodia formation at the cell leading edge, empowering cells to migrate faster. Collectively, our findings reveal that KLF5 controls robust transcription program of ACTN4 to modulate actin remodeling and augment cell motility which enhances NPC metastasis, and provide new potential biomarkers and therapeutic interventions for NPC.

Intentional wedge resection versus segmentectomy for ≤2 cm Ground-Glass-Opacity-Dominant Non-Small cell lung cancer: a Real-World study using inverse probability of treatment weighting.

BACKGROUND: Whether wedge resection is oncological suitable for ground glass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) ≤2 cm is still debatable. The aim of this study is to investigate the short-term and long-term outcomes of intentional wedge resection and segmentectomy for those patients. MATERIALS AND METHODS: This was a real-world study from one of the largest thoracic surgery centers in XX. Patients who underwent intentional wedge resection or segmentectomy for ≤2 cm CTR(consolidation-to-tumor)≤0.5 NSCLC were consecutively included between December 2009 and December 2018. Data were prospectively collected and retrospectively reviewed. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS) and lung cancer-specific survival (LCSS), were analyzed using Cox proportional model. RESULTS: A total of 1209 patients were included (497 in the wedge resection group, 712 in the segmentectomy group). Compared to segmentectomy, wedge resection had a significantly lower rate of complications (3.8% vs. 7.7%, P=0.008), a shorter operating time (65min vs. 114min, P<0.001), and a shorter postoperative stay (3d vs. 4d, P<0.001). The median follow-up was 70.1 months. The multivariate Cox model indicated that wedge resection had survival outcomes that were similar to segmentectomy in terms of 5-year OS (98.8% vs. 99.6%, HR=1.98, 95%CI: 0.59-6.68, P=0.270), 5-year RFS (98.8% vs. 99.5%, HR=1.88, 95%CI: 0.56-6.31, P=0.307) and 5-year LCSS (99.9% vs. 99.6%, HR=1.76, 95%CI: 0.24-13.15, P=0.581). CONCLUSION: Intentional wedge resection is an appropriate choice for ≤2 cm GGO-dominant NSCLC.

Mixed-ligand-functionalized silicon-germanium alloy nanocrystals with improved carrier mobilities.

Silicon-germanium (SiGe) alloy nanocrystals (NCs) are promising for advanced optoelectronic applications due to their highly tunable composition and photophysical behaviors. The homogenous dispersion of Si and Ge atoms on the surfaces of SiGe NCs adds a degree of freedom for manipulating the surface chemistry of this type of alloy material. However, the difference in the reactivity between Si and Ge atoms brings additional difficulty in selecting appropriate surface ligands to passivate SiGe NCs. Here we report a mixed-ligand functionalization approach to passivate SiGe NCs effectively. Octadecene and oleylamine molecules serve as co-ligands to cap the surface Si and Ge atoms, respectively, yielding colloidally stable SiGe NCs with high solution dispersity and stable intrinsic near-infrared emission with a microsecond-scale lifetime decay. The resulting particles also show improved hole and electron mobilities of up to 1.1 × 10-6 cm2 V-1 s-1 and 6.3 × 10-6 cm2 V-1 s-1, 2.2 and 1.2 times improvement over the particles only passivated by octadecene ligands.

Zinc-doped bioactive glass-functionalized polyetheretherketone to enhance the biological response in bone regeneration.

Polyether ether ketone (PEEK) is gaining recognition as a highly promising polymer for orthopedic implants, attributed to its exceptional biocompatibility, ease of processing, and radiation resistance. However, its long-term in vivo application faces challenges, primarily due to suboptimal osseointegration from postimplantation inflammation and immune reactions. Consequently, biofunctionalization of PEEK implant surfaces emerges as a strategic approach to enhance osseointegration and increase the overall success rates of these implants. In our research, we engineered a multifaceted PEEK implant through the in situ integration of chitosan-coated zinc-doped bioactive glass nanoparticles (Zn-BGNs). This novel fabrication imbues the implant with immunomodulatory capabilities while bolstering its osseointegration potential. The biofunctionalized PEEK composite elicited several advantageous responses; it facilitated M2 macrophage polarization, curtailed the production of inflammatory mediators, and augmented the osteogenic differentiation of bone marrow mesenchymal stem cells. The experimental findings underscore the vital and intricate role of biofunctionalized PEEK implants in preserving normal bone immunity and metabolism. This study posits that utilizing chitosan-BGNs represents a direct and effective method for creating multifunctional implants. These implants are designed to facilitate biomineralization and immunomodulation, making them especially apt for orthopedic applications.

Enhancing Fat Transplantation Efficiency in a Mouse Model through Pretreatment of Adipose-Derived Stem Cells with RIP3 Inhibitors.

BACKGROUND: Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. OBJECTIVES: This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. METHODS: ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. RESULTS: The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1ß), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. CONCLUSIONS: These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

DNM3OS/miR-127-5p/CDH11, activates Wnt3a/ß-catenin/LEF-1 pathway to form a positive feedback and aggravate spine facet joint osteoarthritis.

Spinal facet joint osteoarthritis (FJOA) is an OA disease with pathogenesis and progression uncovered. Our present study was performed to elucidate the role of DNM3OS on spinal FJOA. In this study, spine facet joint tissue of patients were collected. In vitro and in vivo models were constructed with SW1353 cells and rats. Hematoxylin and eosin (HE) staining, Safranin O-fast Green, Alcian blue staining, and Tolueine blue O (TBO) staining were employed for histology analyses. Quantitative PCR, western blotting, and Immunofluorescence were performed to evaluate the expression of genes. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay analysis. Cell Counting Kit-8 and flow cytometry were used for cell activity and apoptosis evaluation. The targeting sites between microRNA (miR)-127-5p and cadherin 11 (CDH11) were predicted TargetScan and miRbase database and confirmed by Dual-luciferase reporter assays. CHIP and EMS assay were employed to confirm the binding of LEF1and DNM3OS promoter. Our results showed that DNM3OS was found to upregulated, while miR-127-5p was downregulated in severe FJOA patients and inflammation-induced chondrosarcoma SW1353 cells. DNM3OS reduced cell activity, induced cell apoptosis and extracellular matrix (ECM) degradation by sponging miR-127-5p in vitro. miR-127-5p targeted CDH11 and inhibited wnt3a/ß-catenin pathway to regulate OA in vitro. LEF1 promoted DNM3OS transcription to form a positively feedback in activated wnt3a/ß-catenin pathway. In vivo rat model also confirmed that DNM3OS aggravated FJOA. In summary, DNM3OS/miR-127-5p/CDH11 enhanced Wnt3a/ß-Catenin/LEF-1 pathway to form a positive feedback and aggravate spinal FJOA.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

Prognostic value of different discretization parameters in 18fluorodeoxyglucose positron emission tomography radiomics of oropharyngeal squamous cell carcinoma.

Purpose: We aim to interrogate the role of positron emission tomography (PET) image discretization parameters on the prognostic value of radiomic features in patients with oropharyngeal cancer. Approach: A prospective clinical trial (NCT01908504) enrolled patients with oropharyngeal squamous cell carcinoma (N=69; mixed HPV status) undergoing definitive radiotherapy and evaluated intra-treatment 18fluorodeoxyglucose PET as a potential imaging biomarker of early metabolic response. The primary tumor volume was manually segmented by a radiation oncologist on PET/CT images acquired two weeks into treatment (20 Gy). From this, 54 radiomic texture features were extracted. Two image discretization techniques-fixed bin number (FBN) and fixed bin size (FBS)-were considered to evaluate systematic changes in the bin number ({32, 64, 128, 256} gray levels) and bin size ({0.10, 0.15, 0.22, 0.25} bin-widths). For each discretization-specific radiomic feature space, an LASSO-regularized logistic regression model was independently trained to predict residual and/or recurrent disease. The model training was based on Monte Carlo cross-validation with a 20% testing hold-out, 50 permutations, and minor-class up-sampling to account for imbalanced outcomes data. Performance differences among the discretization-specific models were quantified via receiver operating characteristic curve analysis. A final parameter-optimized logistic regression model was developed by incorporating different settings parameterizations into the same model. Results: FBN outperformed FBS in predicting residual and/or recurrent disease. The four FBN models achieved AUC values of 0.63, 0.61, 0.65, and 0.62 for 32, 64, 128, and 256 gray levels, respectively. By contrast, the average AUC of the four FBS models was 0.53. The parameter-optimized model, comprising features joint entropy (FBN = 64) and information measure correlation 1 (FBN = 128), achieved an AUC of 0.70. Kaplan-Meier analyses identified these features to be associated with disease-free survival (p=0.0158 and p=0.0180, respectively; log-rank test). Conclusions: Our findings suggest that the prognostic value of individual radiomic features may depend on feature-specific discretization parameter settings.

Full Stokes polarimetry based on an inverse-designed multi-foci metalens.

In the realm of metasurface-based polarimetry, well-known for its remarkable compactness and integration capabilities, previous attempts have been hindered by limitations such as the restricted choices of target polarization states and the inefficient focusing of light. To address these problems, this study introduces and harnesses a novel, to our knowledge, forward-solving model, grounded in the equivalence principle and dyadic Green's function, to inversely optimize the vectorial focusing patterns of metalenses. Leveraging this methodology, we develop and experimentally validate a single multi-foci metalens-based polarimeter, capable of simultaneously separating and concentrating four distinct elliptical polarization states at a wavelength of 10.6 µm. Rigorous experimental evaluations, involving the assessment of 18 scalar polarized beams, reveal an average error of 5.92% and a high contrast ratio of 0.92, which demonstrates the efficacy of the polarimeter. The results underscore the potential of our system in diverse sectors, including military defense, healthcare, and autonomous vehicle technology.

The return on investment for the prevention and treatment of childhood and adolescent overweight and obesity in China: a modelling study.

Background: The rapid increase in child and adolescent overweight and obesity (OAO) in China has a significant health and economic impact. This study undertook an investment case analysis to evaluate the health and economic impacts of child and adolescent OAO in China and the potential health and economic returns from implementing specific policies and interventions. Methods: The analysis estimates the reduction in mortality and morbidity from implementing a set of evidence-based interventions across China between 2025 and 2092 using a deterministic Markov cohort model. Modelled interventions were identified by literature review and expert recommendation and include fiscal and regulatory policies, eHealth breastfeeding promotion, school-based interventions, and nutritional counselling by physicians. The study applies a societal costing perspective to model the economic impact on healthcare cost savings, wages, and productivity during adulthood. By projecting and comparing the costs between a status quo scenario and an intervention scenario, the study estimates the return on investment (ROI) for interventions separately and in combination. Findings: Without intervention China will experience 3.3 billion disability-adjusted life years (DALYs) due its current levels of child and adolescent OAO and a lifetime economic impact of CNY 218 trillion (USD 31.6 trillion), or a lifetime CNY 2.5 million loss per affected child or adolescent (USD 350 thousand). National implementation of all five interventions would avert 179.4 million DALYs and result in CNY 13.1 trillion of benefits over the model cohort's lifetime. Implementing fiscal and regulatory policies had the strongest ROI, with benefits accruing at least 10 years after implementation. Scaling up China's current school-based interventions offers China significant health and economic gains, however, the ROI is lower than other modelled interventions. Interpretation: Effective prevention and treatment of child and adolescent OAO is critical to China's health and economic development. Multiple interventions offer a comprehensive approach to address the various factors that increase risk of child and adolescent OAO. Nonetheless, fiscal and regulatory policies offer the strongest health and economic gains. Funding: Funding was provided by UNICEF China.

Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.