A GAPDH serotonylation system couples CD8+ T cell glycolytic metabolism to antitumor immunity.

Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8+ T cells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction. Serotonylation supports the cytoplasmic localization of GAPDH, which induces a glycolytic metabolic shift in CD8+ T cells and contributes to antitumor immunity. CD8+ T cells accumulate intracellular 5-HT for serotonylation through both synthesis by tryptophan hydroxylase 1 (TPH1) and uptake from the extracellular compartment via serotonin transporter (SERT). Monoamine oxidase A (MAOA) degrades 5-HT and acts as an intrinsic negative regulator of CD8+ T cells. The adoptive transfer of 5-HT-producing TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our findings expand the known range of neuroimmune interaction patterns by providing evidence of receptor-independent serotonylation post-translational modification.

Causal associations of COVID-19 on neurosurgical diseases risk: a Mendelian randomization study.

Many researchers have explored the potential association between one neurosurgical disease and coronavirus disease 2019 (COVID-19), but few systematically analyzed the association and causality between COVID-19 and various neurosurgical diseases. A Mendelian randomization analysis was conducted to evaluate the causal association between COVID-19 (including critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 30 neurosurgical diseases within European populations. The consequences of inverse variance weighted models suggest that genetic susceptibility of critically ill COVID-19 may increase the risk of cerebral infarction (odds ratio [OR] = 1.02; p-value = 0.006), genetic susceptibility of SARS-CoV-2 infection may increase the risk of stroke (OR = 1.02; p-value = 0.047), and conversely, genetic susceptibility of hospitalized COVID-19 may reduce the risk of pituitary adenoma and craniopharyngioma (OR = 0.90; p-value = 0.032). In addition, evidences revealed potential associations between genetic susceptibility of COVID-19 and spinal stenosis (OR = 1.03; p-value = 0.028), diffuse brain injury (OR = 1.21; p-value = 0.040) and focal brain injury (OR = 1.12; p-value = 0.040). By testing for heterogeneity and pleiotropy, the above causal conclusions are robust. In summary, our analysis shows that COVID-19 has an independent and powerful causal influence on multiple neurosurgical disorders.

PAK inhibitor FRAX486 decreases the metastatic potential of triple-negative breast cancer cells by blocking autophagy.

BACKGROUND: Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with a high risk of metastasis and recurrence and a poor prognosis. Epithelial-mesenchymal transition (EMT) endows epithelial cells with the ability to move to distant sites, which is essential for the metastasis of TNBC to organs, including the lung. Autophagy, an intracellular degradation process that involves formation of double-layered lipid autophagosomes that transport cytosolic cargoes into lysosomes via autophagosome-lysosome fusion, is involved in various diseases, including cancer and neurodegenerative, metabolic, cardiovascular, and infectious diseases. The relationship between autophagy and cancer has become relatively clear. However, research on pharmacological drugs that block cancer EMT by targeting autophagy is still in the initial stages. Therefore, the re-evaluation of old drugs for their potential in blocking both autophagy and EMT was conducted. METHODS: More than 2000 small molecule chemicals were screened for dual autophagy/EMT inhibitors, and FRAX486 was identified as the best candidate inhibitor of autophagy/EMT. The functions of FRAX486 in TNBC metastasis were detected by CCK-8, migration and wound healing assays. The effects of FRAX486 on autophagy and its target PAK2 were determined by immunoblotting, immunofluorescence, immunoprecipitation analysis and transmission electron microscopy. The findings were validated in mouse models. RESULTS: Here, we report that FRAX486, a potent P21-activated kinase 2 (PAK2) inhibitor, facilitates TNBC suppression both in vitro and in vivo by blocking autophagy. Mechanistically, FRAX486 inhibits autophagy in TNBC cells by targeting PAK2, leading to the ubiquitination and proteasomal degradation of STX17, which mediates autophagosome-lysosome fusion. The inhibition of autophagy by FRAX486 causes upregulation of the epithelial marker protein E-cadherin and thus suppresses the migration and metastasis of TNBC cells. CONCLUSIONS: The effects of FRAX486 on TNBC metastasis suppression were verified to be dependent on PAK2 and autophagy inhibition. Together, our results provide a molecular basis for the application of FRAX486 as a potential treatment for inhibiting the metastasis of TNBC.

Nucleolar HEAT Repeat Containing 1 Up-regulated by the Mechanistic Target of Rapamycin Complex 1 Signaling Promotes Hepatocellular Carcinoma Growth by Dominating Ribosome Biogenesis and Proteome Homeostasis.

BACKGROUND & AIMS: Hyperactivation of ribosome biogenesis leads to hepatocyte transformation and plays pivotal roles in hepatocellular carcinoma (HCC) development. We aimed to identify critical ribosome biogenesis proteins that are overexpressed and crucial in HCC progression. METHODS: HEAT repeat containing 1 (HEATR1) expression and clinical correlations were analyzed using The Cancer Genome Atlas and Gene Expression Omnibus databases and further evaluated by immunohistochemical analysis of an HCC tissue microarray. Gene expression was knocked down by small interfering RNA. HEATR1-knockdown cells were subjected to viability, cell cycle, and apoptosis assays and used to establish subcutaneous and orthotopic tumor models. Chromatin immunoprecipitation and quantitative polymerase chain reaction were performed to detect the association of candidate proteins with specific DNA sequences. Endogenous coimmunoprecipitation combined with mass spectrometry was used to identify protein interactions. We performed immunoblot and immunofluorescence assays to detect and localize proteins in cells. The nucleolus ultrastructure was detected by transmission electron microscopy. Click-iT (Thermo Fisher Scientific) RNA imaging and puromycin incorporation assays were used to measure nascent ribosomal RNA and protein synthesis, respectively. Proteasome activity, 20S proteasome foci formation, and protein stability were evaluated in HEATR1-knockdown HCC cells. RESULTS: HEATR1 was the most up-regulated gene in a set of ribosome biogenesis mediators in HCC samples. High expression of HEATR1 was associated with poor survival and malignant clinicopathologic features in patients with HCC and contributed to HCC growth in vitro and in vivo. HEATR1 expression was regulated by the transcription factor specificity protein 1, which can be activated by insulin-like growth factor 1-mammalian target of rapamycin complex 1 signaling in HCC cells. HEATR1 localized predominantly in the nucleolus, bound to ribosomal DNA, and was associated with RNA polymerase I transcription/processing factors. Knockdown of HEATR1 disrupted ribosomal RNA biogenesis and impaired nascent protein synthesis, leading to reduced cytoplasmic proteasome activity and inhibitory-κB/nuclear factor-κB signaling. Moreover, HEATR1 knockdown induced nucleolar stress with increased nuclear proteasome activity and inactivation of the nucleophosmin 1-MYC axis. CONCLUSIONS: Our study revealed that HEATR1 is up-regulated by insulin-like growth factor 1-mammalian target of rapamycin complex 1-specificity protein 1 signaling in HCC and functions as a crucial regulator of ribosome biogenesis and proteome homeostasis to promote HCC development.

Autophagy-related CMTM6 promotes glioblastoma progression by activating Wnt/ß-catenin pathway and acts as an onco-immunological biomarker.

BACKGROUND: Glioblastoma multiforme (GBM) is identified as one of the most prevalent and malignant brain tumors, characterized by poor treatment outcomes and a limited prognosis. CMTM6, a membrane protein, has been found to upregulate the expression of programmed cell death 1 ligand 1 protein (PD-L1) and acts as an immune checkpoint inhibitor by inhibiting the programmed death 1 protein/PD-L1 signaling pathway. Recent research has demonstrated a high expression of CMTM6 in GBM, suggesting its potential role in influencing the pathogenesis and progression of GBM, as well as its association with immune cell infiltration in the tumor microenvironment. However, the underlying mechanism of CMTM6 in GBM requires further investigation. METHODS: Data from cancer patients in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas cohorts were consolidated for the current study. Through multi-omics analysis, the study systematically examined the expression profile of CMTM6, epigenetic modifications, prognostic significance, biological functions, potential mechanisms of action and alterations in the immune microenvironment. Additionally, the study investigated CMTM6 expression in GBM cell lines and normal cells using reverse transcription PCR and western blot analysis. The impact of CMTM6 on GBM cell proliferation, migration and invasion was evaluated using a combination of cell counting kit-8 assay, clone formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, wound healing assay and Transwell assay. In order to explore the mechanism of CMTM6, the Wnt/ß-catenin signaling pathway and autophagy-related genes were further verified through western blot analysis. RESULTS: CMTM6 is highly expressed in multiple tumors, particularly GBM. CMTM6 has been shown to be a valuable diagnostic and prognostic biomarker by various bioinformatics approaches. Additionally, CMTM6 plays a pivotal role in the pathogenesis of cancer, specifically GBM, by modulating various biological processes such as DNA methyltransferase expression, RNA modification, copy number variation, genomic heterogeneity, tumor stemness and DNA methylation. The findings of the experiment indicate a significant correlation between elevated CMTM6 expression and the proliferation, invasion, migration and autophagy of GBM cells, with potential key roles mediated through the Wnt/ß-catenin signaling pathway. Furthermore, CMTM6 is implicated in modulating tumor immune cell infiltration and is closely linked to the expression of various immune checkpoint inhibitors and immune modulators, particularly within the context of GBM. High levels of CMTM6 expression also enhance the responsiveness of GBM patients to radiotherapy and chemotherapy, thereby offering valuable insights for guiding treatment strategies for GBM. CONCLUSIONS: Autophagy-related CMTM6 is highly expressed in various types of cancer, especially GBM, and it can regulate GBM progression through the Wnt/ß-catenin signaling pathway and is capable of being used as an underlying target for the diagnosis, treatment selection and prognosis of patients with GBM.

Predicting the onset of breast cancer using mammogram imaging data with irregular boundary.

With mammography being the primary breast cancer screening strategy, it is essential to make full use of the mammogram imaging data to better identify women who are at higher and lower than average risk. Our primary goal in this study is to extract mammogram-based features that augment the well-established breast cancer risk factors to improve prediction accuracy. In this article, we propose a supervised functional principal component analysis (sFPCA) over triangulations method for extracting features that are ordered by the magnitude of association with the failure time outcome. The proposed method accommodates the irregular boundary issue posed by the breast area within the mammogram imaging data with flexible bivariate splines over triangulations. We also provide an eigenvalue decomposition algorithm that is computationally efficient. Compared to the conventional unsupervised FPCA method, the proposed method results in a lower Brier Score and higher area under the ROC curve (AUC) in simulation studies. We apply our method to data from the Joanne Knight Breast Health Cohort at Siteman Cancer Center. Our approach not only obtains the best prediction performance comparing to unsupervised FPCA and benchmark models but also reveals important risk patterns within the mammogram images. This demonstrates the importance of utilizing additional supervised image-based features to clarify breast cancer risk.

Pectoral muscle removal in mammogram images: A novel approach for improved accuracy and efficiency.

PURPOSE: Accurate pectoral muscle removal is critical in mammographic breast density estimation and many other computer-aided algorithms. We propose a novel approach to remove pectoral muscles form mediolateral oblique (MLO) view mammograms and compare accuracy and computational efficiency with existing method (Libra). METHODS: A pectoral muscle identification pipeline was developed. The image is first binarized to enhance contrast and then the Canny algorithm was applied for edge detection. Robust interpolation is used to smooth out the pectoral muscle region. Accuracy and computational speed of pectoral muscle identification was assessed using 951 women (1,902 MLO mammograms) from the Joanne Knight Breast Health Cohort at Washington University School of Medicine. RESULTS: Our proposed algorithm exhibits lower mean error of 12.22% in comparison to Libra's estimated error of 20.44%. This 40% gain in accuracy was statistically significant (p < 0.001). The computational time for the proposed algorithm is 5.4 times faster when compared to Libra (5.1 s for proposed vs. 27.7 s for Libra per mammogram). CONCLUSION: We present a novel approach for pectoral muscle removal in mammogram images that demonstrates significant improvement in accuracy and efficiency compared to existing method. Our findings have important implications for the development of computer-aided systems and other automated tools in this field.

Single femtosecond pulse writing of a bifocal lens.

In this Letter, a method for the fabrication of bifocal lenses is presented by combining surface ablation and bulk modification in a single laser exposure followed by the wet etching processing step. The intensity of a single femtosecond laser pulse was modulated axially into two foci with a designed computer-generated hologram (CGH). Such pulse simultaneously induced an ablation region on the surface and a modified volume inside the fused silica. After etching in hydrofluoric acid (HF), the two exposed regions evolved into a bifocal lens. The area ratio (diameter) of the two lenses can be flexibly adjusted via control of the pulse energy distribution through the CGH. Besides, bifocal lenses with a center offset as well as convex lenses were obtained by a replication technique. This method simplifies the fabrication of micro-optical elements and opens a highly efficient and simple pathway for complex optical surfaces and integrated imaging systems.

Modeling correlated pairs of mammogram images.

Mammography remains the primary screening strategy for breast cancer, which continues to be the most prevalent cancer diagnosis among women globally. Because screening mammograms capture both the left and right breast, there is a nonnegligible correlation between the pair of images. Previous studies have explored the concept of averaging between the pair of images after proper image registration; however, no comparison has been made in directly utilizing the paired images. In this paper, we extend the bivariate functional principal component analysis over triangulations to jointly characterize the pair of imaging data bounded in an irregular domain and then nest the extracted features within the survival model to predict the onset of breast cancer. The method is applied to our motivating data from the Joanne Knight Breast Health Cohort at Siteman Cancer Center. Our findings indicate that there was no statistically significant difference in model discrimination performance between averaging the pair of images and jointly modeling the two images. Although the breast cancer study did not reveal any significant difference, it is worth noting that the methods proposed here can be readily extended to other studies involving paired or multivariate imaging data.

Serum selenium and fasting blood glucose: a cross-sectional study in women of different menopause status.

BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.

Multi-mode stable, high peak power Nd:YAG laser device for laser cleaning.

High average power and peak power solid-state lasers are of great interest in the field of laser cleaning. In this research, a high peak power laser with over 400 W average power using a multi-mode stable resonator in a diode-pumped Nd:YAG master oscillator power amplifier has been demonstrated. A maximum peak power over 1.08 MW was achieved at a repetition frequency of 5 kHz. Delivery fiber with a 400 µm core diameter was utilized for flexible laser transmission. A prototype of the laser cleaning system was developed and inspiring application effects for paint and mold cleaning were achieved.

Transcriptome analysis reveals the mechanism of antifungal peptide epinecidin-1 against Botrytis cinerea by mitochondrial dysfunction and oxidative stress.

The marine antifungal peptide epinecidin-1 (EPI) have been shown to inhibit Botrytis cinerea growth, while the molecular mechanism have not been explored based on omics technology. This study aimed to investigate the molecular mechanism of EPI against B. cinerea by transcriptome technology. Our findings indicated that a total of 1671 differentially expressed genes (DEGs) were detected in the mycelium of B. cinerea treated with 12.5 µmol/L EPI for 3 h, including 773 up-regulated genes and 898 down-regulated genes. Cluster analysis showed that DEGs (including steroid biosynthesis, (unsaturated) fatty acid biosynthesis) related to cell membrane metabolism were significantly down-regulated, and almost all DEGs involved in DNA replication were significantly inhibited. In addition, it also induced the activation of stress-related pathways, such as the antioxidant system, ATP-binding cassette transporter (ABC) and MAPK signaling pathways, and interfered with the tricarboxylic acid (TCA) cycle and oxidative phosphorylation pathways related to mitochondrial function. The decrease of mitochondrial related enzyme activities (succinate dehydrogenase, malate dehydrogenase and adenosine triphosphatase), the decrease of mitochondrial membrane potential and the increase content of hydrogen peroxide further confirmed that EPI treatment may lead to mitochondrial dysfunction and oxidative stress. Based on this, we speculated that EPI may impede the growth of B. cinerea through its influence on gene expression, and may lead to mitochondrial dysfunction and oxidative stress.

Systemic immune-inflammation index is associated with ulcerative plaque in patients with acute ischemic stroke: A single center exploratory study.

PURPOSE: This study explored the correlation between inflammatory markers and ulcerative plaques based on carotid doppler ultrasound (CDU) in individuals with acute ischemic stroke (AIS). METHODS: A total of 202 cases diagnosed with AIS associated with atherosclerotic plaque (AP) in the carotid artery were enrolled in this research. Collecting clinical baseline data, laboratory data (such as the complete blood count) and imaging data (CDU and Brain magnetic resonance imaging [MRI]). Then the correlation between Systemic immune-inflammation index (SII, SII = P N/L, where P, N, and L were the peripheral blood platelet, neutrophil and lymphocyte counts, respectively), the shape and position of AP, the degree of carotid artery stenosis, and the presence of ulcerative plaques. Cutoff values were determined accordingly. RESULTS: SII and high sensitivity CRP (hs-CRP) were independent risk factors for the presence of vulnerable carotid plaques. SII, type A plaque, plaque above carotid bifurcation, and severe carotid stenosis were independent risk factors for the presence of ulcerative plaque. The AUC value, the sensitivity, specificity, the best cutoff value of SII in predicting the presence of ulcerative plaque was 0.895, 93.3%, 89.2%, and 537.4 (109 /L), respectively. CONCLUSION: SII at admission was found to be independently associated with the presence of AIS with vulnerable plaque, especially ulcerative plaques. Moreover, plaque ulceration was more likely to form when the area of higher plaque thickness was located in the upstream arterial wall of maximum plaque thickness (WTmax), plaque was above the carotid bifurcation and severe carotid stenosis.

CXC chemokine ligand-10 promotes the accumulation of monocyte-like myeloid-derived suppressor cells by activating p38 MAPK signaling under tumor conditions.

CXC chemokine ligand-10 (CXCL10) is a small (10 kDa) secretory protein in the CXC subfamily of cytokines. CXCL10 has been reported to play an important role in antitumor immunity as a chemotactic factor. Tumor development is always accompanied by the formation of an immunosuppressive tumor microenvironment, and the role of CXCL10 in tumor immunosuppression remains unclear. Here, we reported that CXCL10 expression was significantly upregulated in mice with melanoma, and tumor cells secreted large amounts of CXCL10. Myeloid-derived suppressor cells (MDSCs) are an important part of the immunosuppressive tumor microenvironment. Our results showed that CXCL10 promoted the proliferation of monocyte-like (mo)-MDSCs by activating the p38 MAPK signaling pathway through CXCR3, which led to the abnormal accumulation of mo-MDSCs under tumor conditions. This finding provides a new understanding of the mechanism by which a tumor-induced immunosuppressive microenvironment forms and suggests that CXCL10 could be a potential intervention target for slowing tumor progression.

Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling.

BACKGROUND: PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated. METHODS: By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes. RESULTS: PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell-cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs. CONCLUSIONS: Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.

The physiology, pathology and potential therapeutic application of serotonylation.

The classical neurotransmitter serotonin or 5-hydroxytryptamine (5-HT), synthesized from tryptophan, can be produced both centrally and peripherally. Through binding to functionally distinct receptors, serotonin is profoundly implicated in a number of fundamental physiological processes and pathogenic conditions. Recently, serotonin has been found covalently incorporated into proteins, a newly identified post-translational modification termed serotonylation. Transglutaminases (TGMs), especially TGM2, are responsible for catalyzing the transamidation reaction by transferring serotonin to the glutamine residues of target proteins. Small GTPases, extracellular matrix protein fibronectin, cytoskeletal proteins and histones are the most reported substrates for serotonylation, and their functions are triggered by this post-translational modification. This Review highlights the roles of serotonylation in physiology and diseases and provides perspectives for pharmacological interventions to ameliorate serotonylation for disease treatment.

Adherence to healthy diet and risk of cardiovascular disease in adult survivors of childhood cancer in the St. Jude Lifetime Cohort: a cross-sectional study.

BACKGROUND: Whether diet has beneficial effects on cardiovascular disease (CVD) in childhood cancer survivors as in the general population is unknown. Therefore, we examined associations between dietary patterns and risk of CVD in adult survivors of childhood cancer. METHODS: Childhood cancer survivors, 18-65 years old in the St Jude Lifetime Cohort (1882 men and 1634 women) were included in the analysis. Dietary patterns were defined by the adherence to the Healthy Eating Index (HEI)-2015, Dietary Approaches to Stop Hypertension (DASH), and alternate Mediterranean diet (aMED) based on a food frequency questionnaire at study entry. CVD cases (323 in men and 213 in women) were defined as participants with at least one grade 2 or higher CVD-related diagnosis at baseline. Multivariable logistic regression adjusted for confounders was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of CVD. RESULTS: Greater adherence to HEI-2015 (OR=0.88, 95% CI: 0.75-1.03, per 10 score increment), DASH (OR=0.85, 95% CI: 0.71-1.01, per 10 score increment), and aMED (OR=0.92, 95% CI: 0.84-1.00, each score increment) were, albeit trending towards significance, associated with a lower risk of CVD in women. HEI-2015 was associated with a non-significantly lower risk of CVD in men (ORQ5 vs. Q1=0.80, 95% CI: 0.50-1.28). These dietary patterns were also associated with a lower risk of CVD in survivors with high underlying CVD risk. CONCLUSIONS: As recommended to the general population, a diet rich in plant foods and moderate in animal foods needs to be a part of CVD management and prevention in childhood cancer survivors.

Repeated measures of mammographic density and texture to evaluate prediction and risk of breast cancer: a systematic review of the methods used in the literature.

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk. METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the Quality in Prognostic Studies tool. RESULTS: Twenty articles were included. The Breast Imaging Reporting and Data System and Cumulus were most commonly used for classifying mammographic density and automated assessment was used on more recent digital mammograms. Time between mammograms varied from 1 year to a median of 4.1, and only nine of the studies used more than two mammograms. Several studies showed that adding change of density or mammographic features improved model performance. Variation in risk of bias of studies was highest in prognostic factor measurement and study confounding. CONCLUSION: This review provided an updated overview and revealed research gaps in assessment of the use of texture features, risk prediction, and AUC. We provide recommendations for future studies using repeated measure methods for mammogram images to improve risk classification and risk prediction for women to tailor screening and prevention strategies to level of risk.

Multiple-photon bundle emission in the n-photon Jaynes-Cummings model.

We study the multiple-photon bundle emission in the n-photon Jaynes-Cummings model composed of a two-level system coupled to a single-mode optical field via the n-photon exciting process. Here, the two-level system is strongly driven by a near-resonant monochromatic field, and hence the system can work in the Mollow regime, in which a super-Rabi oscillation between the zero-photon state and the n-photon state can take place under proper resonant conditions. We calculate the photon number populations and the standard equal-time high-order correlation functions, and find that the multiple-photon bundle emission can occur in this system. The multiple-photon bundle emission is also confirmed by investigating the quantum trajectories of the state populations and both the standard and generalized time-delay second-order correlation functions for multiple-photon bundle. Our work paves the way towards the study of multiple-photon quantum coherent devices, with potential application in quantum information sciences and technologies.

Boosting Hydrostability and Carbon Dioxide Capture of Boroxine-Linked Covalent Organic Frameworks by One-Pot Oligoamine Modification.

Boron-based covalent organic frameworks (COFs) are susceptible to nucleophilic attack by water at the electron-deficient boron sites and even slightly humid air could destroy the integrity of their porous frameworks within hours. Such instability is a major limitation to the practical applications of boron-based COFs. Herein we report a significant enhancement of hydrostability of boroxine-linked COFs (COF-1 as representative) by modification with an oligoamine (tetraethylenepentamine, TEPA), which leads to survival of the modified COF in water and long-time stability under humid atmosphere. Meanwhile, the TEPA modification also results in a considerable increase in CO2 adsorption capacity up to 13 times and a dramatic improvement in CO2 /N2 selectivity in low pressure region, which make the modified COF suitable for capturing CO2 from flue gas. This work provides a facile, efficient, and scalable method to greatly improve hydrostability of boroxine-linked COFs and reshape them into high-performance CO2 adsorbents.