Respiratory Syncytial Virus Prefusion F Vaccination: Antibody Persistence and Revaccination.

BACKGROUND: Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well-tolerated and immunogenic in a phase 1/2 study. We evaluated antibody persistence after initial vaccination and safety and immunogenicity after revaccination from this study. METHODS: Healthy adults were randomized to receive both initial vaccination and revaccination 12 months later with either placebo or RSVpreF 240 µg (±Al(OH)3). RSV-A and RSV-B geometric mean neutralizing titers (GMTs) were measured through 12 months after both vaccinations. Tolerability/safety was assessed. RESULTS: There were 263 participants revaccinated (18-49-years-old, n=134; 65-85-years-old, n=129). Among 18-49-year-olds and 65-85-year-olds, respectively, geometric mean fold rises (GMFRs) for both RSV subgroups (RSV-A; RSV-B) 1 month after initial RSVpreF vaccination were 13.3-20.4 and 8.9-15.5 compared with levels before initial vaccination; corresponding GMFRs 12 months after initial vaccination were 4.1-5.0 and 2.6-4.1. GMFRs 1 month after revaccination compared with levels before revaccination were 1.4-2.3 and 1.4-2.2 for 18-49-year-olds and 65-85-year-olds, respectively. Peak GMTs after revaccination were lower than those after initial vaccination. GMTs 12 months after initial vaccination and revaccination were similar, with GMFRs ranging from 0.7-1.6. No safety signals occurred. CONCLUSIONS: RSVpreF revaccination was immunogenic and well-tolerated among adults. NCT03529773.

Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration.

Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.

Novel Patterns in High-Resolution Computed Tomography in Whipple Pneumonia.

With the use of metagenomic next-generation sequencing, patients diagnosed with Whipple pneumonia are being increasingly correctly diagnosed. We report a series of 3 cases in China that showed a novel pattern of movable infiltrates and upper lung micronodules. After treatment, the 3 patients recovered, and lung infiltrates resolved.

Dual anti-angiogenic and anti-inflammatory action of tRNA-Cys-5-0007 in ocular vascular disease.

BACKGROUND: Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis. METHODS: Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. RESULTS: tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-ß1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. CONCLUSIONS: Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy.

Multimodality Cardiovascular Imaging for Totally Video-Guided Thorascopic Cardiac Surgery.

Totally video-guided thorascopic cardiac surgery (TVTCS) represents one of the most minimally invasive access routes to the heart. Its feasibility and safety can be guaranteed by an experienced surgeon with skilled operative techniques under the guidance of a video signal via thoracoscopy and the imaging from transesophageal echocardiography. At present, this surgical approach has been applied for atrioventricular valve disease, atrial septum defects plus and partial anomalous pulmonary venous drainage, cardiac tumors, hypertrophic obstructive cardiomyopathy, aortic valve disease, and atrial fibrillation. Multimodality cardiovascular imaging, including echocardiography, X-ray, computed tomography (CT), magnetic resonance imaging (MRI) and cardiac catheterization, provides morphologic characteristics and function status of the cardiovascular system and a comprehensive view of the target anatomy. In this review, the benefits of multimodality cardiovascular imaging are summarized for the clinical practice of TVTCS, including the preoperative preparation, intraoperative guidance and postoperative supervision. The disease categories are also individually reviewed on the basis of multimodality cardiovascular imaging, to ensure the feasibility and safety for TVTCS. Cardiovascular imaging technologies not only confirm who is a candidate for this surgical technique, but also provide technical support during the procedure and for postop follow to assess the clinical outcomes. Multimodality cardiovascular imaging is instrumental to provide the requirements to solve the problems for conduction of TVTCS; and to provide individualized protocols with high-resolution and real-time dynamic imaging fusion.

Identification of the central role of RNA polymerase mitochondrial for angiogenesis.

Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.

The Efficacy of Traditional Chinese Herbal Medicine Across Multiple Cardiovascular Diseases: An Umbrella Review of Systematic Reviews of Randomized Controlled Trials.

ABSTRACT: Traditional Chinese herbal medicine (CHM) has been extensively used in cardiovascular disease (CVD) in modern clinical practice, alone or in combination with conventional treatment. However, its efficacy has not been assessed extensively. From inception until August 2023, we systematically searched 5 public literature databases to conduct the umbrella review. The inclusion criterion is systematic reviews of randomized controlled trials investigating the effect of CHM in the contemporary management of CVDs. The quality of the included systematic reviews, the certainty of the evidence, and the potential risk of bias were assessed. Five hundred and thirty-nine systematic reviews, including 346 studies in Chinese and 193 in English, were selected before the quantitative synthesis. The methodological quality was generally moderate, with a median value of 11. The favorable efficacy of CHM was primarily presented on 5 main conditions: coronary artery disease, hypertension, heart failure, restenosis, and angina pectoris. CHM, with or without conventional treatment, showed a consistent beneficial effect in various CVDs. Nevertheless, the magnitude of the effect requires further investigation as the lack of relevant research and the complexity of the clinical practice of CHM.

Improved ion adsorption capacities and diffusion dynamics in surface anchored MoS2⊥Mo4/3B2 and MoS2⊥Mo4/3B2O2 heterostructures as anodes for alkaline metal-ion batteries.

First-principles calculations were performed to analyze the atomic structures and electrochemical energy storage properties of novel MoS2⊥boridene heterostructures by anchoring MoS2 nanoflakes on Mo4/3B2 and Mo4/3B2O2 monolayers. Both thermodynamic and thermal stabilities of each heterostructure were thoroughly evaluated from the obtained binding energies and through first-principles molecular dynamics simulations at room temperature, confirming the high formability of the heterostructures. The electrochemical properties of MoS2⊥Mo4/3B2 and MoS2⊥Mo4/3B2O2 heterostructures were investigated for their potential use as anodes for alkaline metal ion batteries (Li+, Na+ and K+). It was revealed that Li+ and Na+ can form multiple stable full adsorption layers on both heterostructures, while K+ forms only a single full adsorption layer. The presence of a negative electron cloud (NEC) contributes to the stabilization of a multi-layer adsorption mechanism. For all investigated alkaline metal ions, the predicted ion diffusion dynamics are relatively sluggish for the adsorbates in the first full adsorption layer on MoS2⊥boridene heterostructures due the relatively large migration energies (>0.50 eV), compared to those of second or third full adsorption layers (<0.30 eV). MoS2⊥Mo4/3B2O2 exhibited higher onset and mean open circuit voltages as anodes for alkaline metal-ion batteries than MoS2⊥Mo4/3B2 hybrids because of enhanced interactions between the adsorbate and the Mo4/3B2O2 monolayer with the presence of O-terminations. Tailoring the size and horizontal spacing between two neighboring MoS2 nano-flakes in heterostructures led to high theoretical capacities for LIBs (531 mA h g-1), SIBs (300 mA h g-1) and PIBs (131 mA h g-1) in the current study.

Keratinocytes stimulate MAIT cells to produce granzyme B via MR1 and cytokines in oral lichen planus.

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease characterized by a dense T-cell infiltration and the degeneration of basal keratinocytes. The potential functions of mucosal associated invariant T (MAIT) cells in OLP have been analyzed in our previous study. Keratinocytes under proinflammatory conditions have been demonstrated to activate T cells. This study was aimed to investigate how keratinocytes stimulate MAIT cells in OLP, and to explore the role of activated MAIT cells on keratinocytes. METHODS AND RESULTS: Increased MAIT cells and higher activation marker CD69 were detected in OLP lesions by flow cytometry. The enhanced expression of MHC class I-like molecule (MR1) required for MAIT cell activation in the epithelial layer of OLP lesions was determined by immunohistochemistry. Keratinocytes treated by 5-A-RU prodrug and lipopolysaccharide, respectively, exhibited higher expression of MR1 and secretion of IL-18. In direct coculture systems consisting of keratinocytes and peripheral blood mononuclear cells, both 5-A-RU prodrug-pretreated keratinocytes and lipopolysaccharide-pretreated keratinocytes activated MAIT cells to secrete granzyme B, contributing to elevated keratinocyte apoptosis. CONCLUSIONS: Keratinocytes were capable to activate MAIT cells via MR1 and cytokines in OLP, and granzyme B produced by activated MAIT cells intensified keratinocyte apoptosis, engaging in the pathogenesis of OLP.

Brain magnetic resonance imaging findings in children with neurological complications of coronavirus disease 2019 (Omicron variant): a multicenter retrospective observational study.

BACKGROUND: An increasing rate of encephalopathy associated with coronavirus disease 2019 (COVID-19) has been observed among children. However, the literature on neuroimaging data in children with COVID-19 is limited. OBJECTIVE: To analyze brain magnetic resonance imaging (MRI) of pediatric COVID-19 patients with neurological complications. MATERIALS AND METHODS: This multicenter retrospective observational study analyzed clinical (n=102, 100%) and neuroimaging (n=93, 91.2%) data of 102 children with COVID-19 infections and comorbid acute neurological symptoms. These children were hospitalized at five pediatric intensive care units (PICUs) in China between December 1, 2022, and January 31, 2023. RESULTS: All patients were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as detected via reverse transcriptase polymerase chain reaction. About 75.7% of the children were infected with the Omicron variant BF.7 strain. Brain MRI was performed 1-12 days following the onset of neurological symptoms, which revealed acute neuroimaging findings in 74.2% (69/93) of cases, including evidence of acute necrotizing encephalopathy (33/69, 47.8%), encephalitis (31/69, 44.9%), reversible splenial lesion syndrome (3/69, 4.3%), reversible posterior leukoencephalopathy (1/69, 1.4%), and hippocampal atrophy (1/69, 1.4%). CONCLUSIONS: Overall, these data highlighted five neuroimaging patterns associated with the outbreak of the SARS-CoV-2 Omicron variant, with acute necrotizing encephalopathy being the most common of these neuroimaging findings. Rarely, the brain MRI of these pediatric COVID-19 patients also demonstrate hippocampal atrophy.

Oral Malassezia infection co-occurring with tinea versicolor: metagenomic sequencing of the saliva.

Malassezia is a lipid-dependent cutaneous symbiotic fungal genus associated with tinea versicolor. Here, we first present a rare case of a young tinea versicolor patient with oral manifestations presenting as white strips, patches, and pigmentation. The patient had a family history of tinea versicolor and a habit of frequent intake of cream. Histopathologic features and periodic acid-schiff staining of oral lesion indicated oral infection with round budding yeasts with short hyphae. Saliva metagenomic sequencing identified Malassezia and demonstrated the upregulated amount, diversity and activity of inflammatory bacteria. The clinical manifestations of oral Malassezia infection and changes in bacterial communities shed light on the pathogenic role of Malassezia in oral mucosa. In conclusion, we report the first oral Malassezia infection, which broadens the pathogenic cognitive scope of Malassezia and highlights the value of molecular techniques in the diagnostic process.

Inactivation of phosphodiesterase-4B gene in rat nucleus accumbens shell by CRISPR/Cas9 or positive allosteric modulation of the protein affects the motivation to chronically self-administer nicotine.

Large scale human genome wide association studies (GWAS) have identified a growing pool of genes associated with cigarette smoking. One of the most prominent, phosphodiesterase-4B (PDE4B), has been associated with multiple smoking phenotypes. Although PDE4B modulates the half-life of neuronal cAMP, its precise role in smoking behaviors is unknown. To address this knowledge gap, we used a reverse translational approach. We inactivated PDE4B in bilateral medial nucleus accumbens shell (NAcs) neurons by injecting AAV containing a specific gRNA in female transgenic Cas9+ Long Evans rats. These rats then were given 23-h chronic access to nicotine intravenous self-administration (IVSA) under a schedule of increasing fixed ratios (FR). With the increased effort required at FR7, nicotine SA (i.e. active presses and drug infusions) declined significantly in controls, whereas it was maintained in the mutagenized group. A progressive ratio (PR) study also showed significantly greater cumulative nicotine infusions in the PDE4B-edited group. Hence, we hypothesized that enhanced PDE4B protein activity would reduce nicotine IVSA. A positive allosteric modulator, 2-(3-(4-chloro-3-fluorophenyl)-5-ethyl-1H-1,2,4-triazol-1-yl)-N-(3,5-dichlorobenzyl)acetamide (MR-L2), was microinfused into NAcs bilaterally at FR3 or FR5; in both cohorts, MR-L2 acutely reduced nicotine IVSA. In summary, these studies show that the activity of PDE4B regulates the capacity of NAcs to maintain nicotine IVSA in face of the cost of increasing work. This finding and the results of the PR study indicate that PDE4B affects the motivation to obtain nicotine. These reverse translational studies in rats provide insight into the motivational effects of NAcs PDE4B that advance our understanding of the smoking behaviors mapped in human GWAS.

Effect of scapular posterior tilting exercise on scapular muscle activities in men and women with a rounded shoulder posture.

Round-shoulder posture (RSP) is a common postural condition, characterized by protraction, downward rotation, anterior tilting and internal rotation of the scapula. RSP can lead to shoulder dysfunction. Different methods have been proposed for rehabilitating and correcting the altered posture in RSP including stretching, strengthening exercises, and shoulder brace or taping. However, the findings are controversial and studies are ongoing to develop more effective method. The present study is aimed at investigating the effects of scapular posterior tilting (SPT) exercise in different support positions on scapular muscle activities in men and women with RSP. In a prospective observational clinical study, we assessed demographic, basic clinical parameters and study variables of the subjects with RSP (n = 20) (men/women = 9/11) attending Daegu University in Gyeongsan, South Korea. To do so, we compared electromyographic (EMG) activities of lower trapezius and serratus anterior muscles between men and women with RSP during SPT exercise on four different support surfaces to determine any difference in the EMG activities. The results revealed that women showed significant differences in EMG activities in the lower and left upper trapezius and serratus anterior muscles, while men showed significant differences in EMG activity only in the lower trapezius muscle during SPT exercise on four different surfaces (P < 0.05). The post-hoc analysis revealed significantly greater EMG activity values in the lower trapezius and serratus anterior muscles during SPT exercise on the upper body unstable surface and whole-body unstable surface (p < 0.05). Independent t-tests after the Bonferroni correction showed no significant differences in muscle activities between men and women on the four different surfaces (p > 0.0125).

A nomogram model for predicting the risk of axillary lymph node metastasis in patients with early breast cancer and cN0 status.

Axillary staging is commonly performed via sentinel lymph node biopsy for patients with early breast cancer (EBC) presenting with clinically negative axillary lymph nodes (cN0). The present study aimed to investigate the association between axillary lymph node metastasis (ALNM), clinicopathological characteristics of tumors and results from axillary ultrasound (US) scanning. Moreover, a nomogram model was developed to predict the risk for ALNM based on relevant factors. Data from 998 patients who met the inclusion criteria were retrospectively reviewed. These patients were then randomly divided into a training and validation group in a 7:3 ratio. In the training group, receiver operating characteristic curve analysis was used to identify the cutoff values for continuous measurement data. R software was used to identify independent ALNM risk variables in the training group using univariate and multivariate logistic regression analysis. The selected independent risk factors were incorporated into a nomogram. The model differentiation was assessed using the area under the curve (AUC), while calibration was evaluated through calibration charts and the Hosmer-Lemeshow test. To assess clinical applicability, a decision curve analysis (DCA) was conducted. Internal verification was performed via 1000 rounds of bootstrap resampling. Among the 998 patients with EBC, 228 (22.84%) developed ALNM. Multivariate logistic analysis identified lymphovascular invasion, axillary US findings, maximum diameter and molecular subtype as independent risk factors for ALNM. The Akaike Information Criterion served as the basis for both nomogram development and model selection. Robust differentiation was shown by the AUC values of 0.855 (95% CI, 0.817-0.892) and 0.793 (95% CI, 0.725-0.857) for the training and validation groups, respectively. The Hosmer-Lemeshow test yielded P-values of 0.869 and 0.847 for the training and validation groups, respectively, and the calibration chart aligned closely with the ideal curve, affirming excellent calibration. DCA showed that the net benefit from the nomogram significantly outweighed both the 'no intervention' and the 'full intervention' approaches, falling within the threshold probability interval of 12-97% for the training group and 17-82% for the validation group. This underscores the robust clinical utility of the model. A nomogram model was successfully constructed and validated to predict the risk of ALNM in patients with EBC and cN0 status. The model demonstrated favorable differentiation, calibration and clinical applicability, offering valuable guidance for assessing axillary lymph node status in this population.

Non-Coding RNAs: Novel Regulators of Macrophage Homeostasis in Ocular Vascular Diseases.

Ocular neovascularization can impair vision and threaten patients' quality of life. However, the underlying mechanism is far from transparent. In all mammals, macrophages are a population of cells playing pivotal roles in the innate immune system and the first line of defense against pathogens. Therefore, it has been speculated that the disfunction of macrophage homeostasis is involved in the development of ocular vascular diseases. Moreover, various studies have found that non-coding RNAs (ncRNAs) regulate macrophage homeostasis. This study reviewed past studies of the regulatory roles of ncRNAs in macrophage homeostasis in ocular vascular diseases.

An integrated analysis revealing the angiogenic function of TP53I11 in tumor microenvironment.

Despite growing evidence suggesting an important contribution of Tumor Protein P53 Inducible Protein 11 (TP53I11) in cancer progression, the role of TP53I11 remains unclear. Our first pan-cancer analysis of TP53I11 showed some tumor tissues displayed reduced TP53I11 expression compared to normal tissues, while others exhibited high TP53I11 expression. Meanwhile, TP53I11 expression carries a particular pan-cancer risk, as high TP53I11 expression levels are detrimental to survival for BRCA, KIRP, MESO, and UVM, but to beneficial survival for KIRC. We demonstrated that TP53I11 expression negatively correlates with DNA methylation in most cancers, and the S14 residue of TP53I11 is phosphorylated in several cancer types. Additionally, TP53I11 was found to be associated with endothelial cells in pan-cancer, and functional enrichment analysis provided strong evidence for its role in tumor angiogenesis. In vitro angiogenesis assays confirmed that TP53I11 can promote angiogenic function of human umbilical vein endothelial cells (HUVECs) in vitro. Mechanistic investigations reveal that TP53I11 is transcriptionally up-regulated by HIF2A under hypoxia.

Significance of Aneuploidy in Predicting Prognosis and Treatment Response of Uveal Melanoma.

AIMS: This study aimed to improve personalized treatment strategies and predict survival outcomes for patients with uveal melanoma (UM). BACKGROUND: Copy number aberrations (CNAs) have been considered as a main feature of metastatic UM. OBJECTIVE: This study was designed to explore the feasibility of using copy number variation (CNV) in UM classification, prognosis stratification and treatment response. METHODS: The CNV data in the TCGA-UVM cohort were used to classify the samples. The differentially expressed genes (DEGs) between subtypes were screened by the "Limma" package. The module and hub genes related to aneuploidy score were identified by performing weighted gene co-expression network analysis (WGCNA) on the DEGs. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to train the hub genes for developing a prognosis model for UM. Finally, the expression levels of the screened prognostic key genes were verified in UM cells, and the cell migration and invasion abilities were detected using real-time quantitative PCR (qRT-PCR) and transwell assay. RESULTS: The UM samples were divided into 3 CNV subtypes, which differed significantly in overall survival (OS) and disease-specific survival (DSS). C1 had the shortest OS and DSS and the highest level of immune infiltration. A total of 2036 DEGs were obtained from the three subtypes. Eighty hub genes with the closest correlation with aneuploidy scores were selected by WGCNA. Univariate Cox and LASSO regression-based analyses finally determined eight genes as the key prognostic genes, including HES6, RNASEH2C, NQO1, NUDT14, TTYH3, GJC1, FKBP10, and MRPL24. A prognostic model was developed using the eight genes, demonstrating a strong prediction power. Differences in the response to immunotherapy among patients in different risk groups were significant. We found that high-risk patients were more sensitive to two drugs (Palbociclib_ 1054 and Ribociclib_1632), while low-risk patients were more sensitive to AZD1208_1449, ERK_2440_1713, Mirin_1048, and Selumetinib_1736. CONCLUSION: UM in this study was divided into three CNV subtypes, and a model based on eight aneuploidy score-related genes was established to evaluate the prognosis and drug treatment efficacy of UM patients. The current results may have the potential to help the clinical decision-making process for UM management.

Segmentation of retinal microaneurysms in fluorescein fundus angiography images by a novel three-step model.

Introduction: Microaneurysms serve as early signs of diabetic retinopathy, and their accurate detection is critical for effective treatment. Due to their low contrast and similarity to retinal vessels, distinguishing microaneurysms from background noise and retinal vessels in fluorescein fundus angiography (FFA) images poses a significant challenge. Methods: We present a model for automatic detection of microaneurysms. FFA images were pre-processed using Top-hat transformation, Gray-stretching, and Gaussian filter techniques to eliminate noise. The candidate microaneurysms were coarsely segmented using an improved matched filter algorithm. Real microaneurysms were segmented by a morphological strategy. To evaluate the segmentation performance, our proposed model was compared against other models, including Otsu's method, Region Growing, Global Threshold, Matched Filter, Fuzzy c-means, and K-means, using both self-constructed and publicly available datasets. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union were calculated. Results: The proposed model outperforms other models in terms of accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union. The segmentation results obtained with our model closely align with benchmark standard. Our model demonstrates significant advantages for microaneurysm segmentation in FFA images and holds promise for clinical application in the diagnosis of diabetic retinopathy. Conclusion: The proposed model offers a robust and accurate approach to microaneurysm detection, outperforming existing methods and demonstrating potential for clinical application in the effective treatment of diabetic retinopathy.

Predictive value of stromal tumor-infiltrating lymphocytes in patients with breast cancer treated with neoadjuvant chemotherapy: A meta-analysis.

BACKGROUND: The predictive value of tumor-infiltrating lymphocytes (TILs) in response to neoadjuvant chemotherapy (NAC) for breast cancer (BC) has received increasing attention. Here, a meta-analysis was conducted to evaluate the correlation between the expression of stromal TILs and pathological complete response (pCR) after NAC in BC patients. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched online by using a combination of keywords and free words to screen literature on the expression of stromal TILs and pCR after NAC in patients with BC. The data were extracted and evaluated for quality. Relative risk (RR) was used to evaluate the relationship between the expression of stromal TILs before NAC and pCR in BC patients. Meta-analysis was performed with Review Manager 5.3 and STATA 14.0 software. RESULTS: Eleven studies involving 6039 BC patients were included in the meta-analysis. The results showed a generally high expression of stromal TILs in BC patients, and the pCR rate after NAC in BC patients with a high expression of stromal TILs was significantly higher than that in BC patients with a low expression of stromal TILs [RR = 1.83, 95% confidence interval (CI): 1.69-1.97]. Subgroup analysis based on the molecular subtypes of BC showed that the pCR rate was significantly higher in patients with a high expression of stromal TILs in hormone receptor (HR)-positive BC [RR = 3.23, 95% CI: 2.43-4.30], human epidermal growth factor receptor 2 (HER-2)-positive BC [RR = 1.41, 95% CI: 1.25-1.60], and triple-negative BC [RR = 1.70, 95% CI: 1.53-1.90] than in those with a low expression of stromal TILs. Subgroup analysis based on expression threshold showed that the pCR rate was higher in patients with a high expression of stromal TILs than in patients with a low expression of stromal TILs at different expression thresholds (10% [RR = 1.99, 95% CI: 1.55-2.55], 20%/30% [RR = 1.57, 95% CI: 1.37-1.81], 50%/60% [RR = 1.91, 95% CI: 1.73-2.11]. CONCLUSION: TILs can be used as a predictor of pCR after NAC in patients with BC, and the appropriate high expression threshold of stromal TILs should be selected as the predictive value according to the molecular subtype of BC.

Association of CYP2C19 genotypes with postoperative atrial fibrillation after coronary artery bypass surgery.

This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.