Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study.

BACKGROUND: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels. METHODS: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019. RESULTS: The global age-standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%-0.21%]), while YLLs decreased substantially (average annual percentage change, -3.33% [95% uncertainty interval, -3.38% to -3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income. CONCLUSIONS: Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.

MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription.

BACKGROUND: The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. METHODS: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. RESULTS: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. CONCLUSION: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.

Global PM2.5 Prediction and Associated Mortality to 2100 under Different Climate Change Scenarios.

Ambient fine particulate matter (PM2.5) has severe adverse health impacts, making it crucial to reduce PM2.5 exposure for public health. Meteorological and emissions factors, which considerably affect the PM2.5 concentrations in the atmosphere, vary substantially under different climate change scenarios. In this work, global PM2.5 concentrations from 2021 to 2100 were generated by combining the deep learning technique, reanalysis data, emission data, and bias-corrected CMIP6 future climate scenario data. Based on the estimated PM2.5 concentrations, the future premature mortality burden was assessed using the Global Exposure Mortality Model. Our results reveal that SSP3-7.0 scenario is associated with the highest PM2.5 exposure, with a global concentration of 34.5 µg/m3 in 2100, while SSP1-2.6 scenario has the lowest exposure, with an estimated of 15.7 µg/m3 in 2100. PM2.5-related deaths for individuals under 75 years will decrease by 16.3 and 10.5% under SSP1-2.6 and SSP5-8.5, respectively, from 2030s to 2090s. However, premature mortality for elderly individuals (>75 years) will increase, causing the contrary trends of improved air quality and increased total PM2.5-related deaths in the four SSPs. Our results emphasize the need for stronger air pollution mitigation measures to offset the future burden posed by population age.

Nickel-Catalyzed Decarboxylative Coupling of Redox-Active Esters with Aliphatic Aldehydes.

The addition of alkyl fragments to aliphatic aldehydes is a highly desirable transformation for fragment couplings, yet existing methods come with operational challenges related to the basicity and instability of the nucleophilic reagents commonly employed. We report herein that nickel catalysis using a readily available bioxazoline (BiOx) ligand can catalyze the reductive coupling of redox-active esters with aliphatic aldehydes using zinc metal as the reducing agent to deliver silyl-protected secondary alcohols. This protocol is operationally simple, proceeds under mild conditions, and tolerates a variety of functional groups. Initial mechanistic studies suggest a radical chain pathway. Additionally, alkyl tosylates and epoxides are suitable alkyl precursors to this transformation providing a versatile suite of catalytic reactions for the functionalization of aliphatic aldehydes.

Total lower lip reconstruction with a double mental neurovascular V-Y island advancement flap.

PURPOSE: To assess the effectiveness of double mental V-Y island advancement flaps for total lower lip reconstructions. MATERIALS AND METHODS: During a 6-year period, from 2006 to 2012, total lower lip reconstruction was performed in 12 patients using double mental V-Y island advanced flaps. The resulting lip function and superiority of each flap were analyzed. To assess any cosmetic implications, patients were asked to answer the Appearance Domain section from the University of Washington Quality of Life Questionnaire at least 12 months after discharge from the hospital. RESULTS: All flaps survived completely and no short-term postoperative complications occurred. The mean follow-up time was 34.5 months (range, 15 to 69 months) and there was no recurrence of disease. All patients were capable of consuming a regular oral diet and no patients complained of an inability to eat in a public setting, drooling, or microstomia. The mean preoperative and postoperative open-mouth widths were 4.1 and 3.7 cm, respectively, and the mean reduced open-mouth width was 10%. The intercommissural width varied from 4.6 to 6.8 cm (mean, 5.5 cm). The mean postoperative 2-point discrimination was 11.2 mm (range, 9 to 13 mm). The mean score for the Appearance Domain section was 93.8 (range, 75 to 100). CONCLUSION: The mental V-Y island advancement flap reconstruction is a reliable procedure for total lower lip reconstruction.

Submental versus platysma flap for the reconstruction of complex facial defects following resection of head and neck tumors.

OBJECTIVE: To compare the platysma flap with submental flap in terms of tumor and flap characteristics, operative properties and the functional outcomes. METHODS: A total of 65 patients presented with tumors of head and neck and underwent curative tumor resection with different neck dissections at the Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology of China Medical University; from March 2005 to December 2012 were included in the study. After radical tumor excision and neck dissection the resultant complex defects were reconstructed with either platysma flap or the submental flap. The extent of surgical resection, the type of neck dissection and choice of flap reconstruction was at the discretion of the surgical team. The functional outcomes, operative time and characteristics of both platysma and submental flaps were compared and the statistical tests of significance were applied accordingly. RESULTS: The mean age was 60 years. The complex facial defects of 30 patients were reconstructed with platysma flap and of 35 patients with submental flap. Mean operation time of submental flap including flap harvesting (5.58±1.96hrs) was shorter than platysma flap (6.2±1.4hrs). The majority of the flaps (88-93%) were taken successfully in both groups. Submental flap was associated with significantly higher patients' satisfaction regarding acceptable functional outcomes (p-value 0.027). The mean reduction in mouth opening was significantly smaller in platysma group (0.37 ±0.18cms) than the submental group (0.47±0.16). CONCLUSION: This study demonstrates that both platysma and submental flap techniques can be used for the reconstruction of complex facial defects with the acceptable functional outcome. The platysma flap can be harvested to medium size defects up to 70cm(2) with good mouth opening. The submental flap is simpler, faster with a wider range of application and more acceptable functional outcomes.

Efficient and robust estimation of single-vehicle crash severity: A mixed logit model with heterogeneity in means and variances.

This study delves into the factors that contribute to the severity of single-vehicle crashes, focusing on enhancing both computational speed and model robustness. Utilizing a mixed logit model with heterogeneity in means and variances, we offer a comprehensive understanding of the complexities surrounding crash severity. The analysis is grounded in a dataset of 39,788 crash records from the UK's STATS19 database, which includes variables such as road type, speed limits, and lighting conditions. A comparative evaluation of estimation methods, including pseudo-random, Halton, and scrambled and randomized Halton sequences, demonstrates the superior performance of the latter. Specifically, our estimation approach excels in goodness-of-fit, as measured by ρ2, and in minimizing the Akaike Information Criterion (AIC), all while optimizing computational resources like run time and memory usage. This strategic efficiency enables more thorough and credible analyses, rendering our model a robust tool for understanding crash severity. Policymakers and researchers will find this study valuable for crafting data-driven interventions aimed at reducing road crash severity.

The application of radiomics machine learning models based on multimodal MRI with different sequence combinations in predicting cervical lymph node metastasis in oral tongue squamous cell carcinoma patients.

BACKGROUND: The purpose of this study was to explore preliminary the performance of radiomics machine learning models based on multimodal MRI to predict the risk of cervical lymph node metastasis (CLNM) for oral tongue squamous cell carcinoma (OTSCC) patients. METHODS: A total of 400 patients were enrolled in this study and divided into six groups according to the different combinations of MRI sequences. Group I consisted of patients with T1-weighted images (T1WI) and FS-T2WI (fat-suppressed T2-weighted images), group II consisted of patients with T1WI, FS-T2WI, and contrast enhanced MRI (CE-MRI), group III consisted of patients with T1WI, FS-T2WI, and T2-weighted images (T2WI), group IV consisted of patients with T1WI, FS-T2WI, CE-MRI, and T2WI, group V consisted of patients with T1WI, FS-T2WI, T2WI, and apparent diffusion coefficient map (ADC), and group VI consisted of patients with T1WI, FS-T2WI, CE-MRI, T2WI, and ADC. Machine learning models were constructed. The performance of the models was compared in each group. RESULTS: The machine learning model in group IV including T1WI, FS-T2WI, T2WI, and CE-MRI presented best prediction performance, with AUCs of 0.881 and 0.868 in the two sets. The models with CE-MRI performed better than the models without CE-MRI(I vs. II, III vs. IV, V vs. VI). CONCLUSIONS: The radiomics machine learning models based on CE-MRI showed great accuracy and stability in predicting the risk of CLNM for OTSCC patients.

Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology.

BACKGROUND: Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC. METHODS: In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization. RESULTS: In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells. CONCLUSIONS: CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages.

CCR7 affects the tumor microenvironment by regulating the activation of naïve CD8+ T cells to promote the proliferation of oral squamous cell carcinoma.

BACKGROUND: Head and neck cancer is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, being one of the leading causes of cancer morbidity and mortality worldwide. CC Chemokine receptor 7(CCR7) is a multifunctional G protein-coupled trans-membrane chemokine that affects immune cell chemotaxis, migration, and cancer progression through its interaction with its ligands C-C motif chemokine ligand 19(CCL19) and C-C motif chemokine ligand 21(CCL21). Numerous studies have demonstrated the involvement of CCR7 in the malignant progression of a variety of cancers, reflecting the pro-cancer properties of CCR7. The Cancer Genome Atlas data suggests CCR7 has elevated expression in oral cancer. Specifically, CCR7 expression in tumor microenvironment (TME) may regulate the ability of some immune cells to engage in anti-tumor immune responses. Since CD8+ T cells have become a key immunotherapeutic target, the role of CCR7 in antitumor immune response of naïve CD8+ T cells in TME has not been thoroughly investigated. METHODS: A CCR7 knockout mouse model was constructed, and the mechanism of ccr7 on the regulation of tumor microenvironment by naïve CD8+ T cells was verified under the guidance of single-cell RNA sequencing combined with in vivo animal experiments and in vitro cell experiments. RESULTS: CCR7 is knocked out with impaired tumor growth and altered CD8+ T cell profiles, revealing the importance of this protein in OSCC. CONCLUSIONS: Inhibition of CCR7 enhances CD8+ T cell activation, proliferation, and anti-tumor function, suggesting its potential as a therapeutic target.

Assessment of the quality of life of patients with oral cancer after pectoralis major myocutaneous flap reconstruction with a focus on speech.

PURPOSE: The aim of the present study was to evaluate the quality of life (QoL) of patients with oral cancer who had undergone resection of the tongue and floor of the mouth and reconstruction with the pectoralis major flap. MATERIALS AND METHODS: The present study assessed 21 patients who had undergone pectoralis major flap reconstruction using the University of Washington QoL, version 4, questionnaire. A nonparametric Mann-Whitney U test was used to analyze the data. RESULTS: Of the 12 disease-specific domains, the best 3 scores from the patients were for pain, saliva, and anxiety, and the worst 3 scores were for taste, chewing, and swallowing. The mean UW-QoL composite score was 73.4. Swallowing was considered to be the most important issue within the previous 7 days, followed by chewing and speech. Those patients who had undergone wider excision had poorer speech. CONCLUSIONS: A significant effect was found on the QoL of patients with oral cancer who had undergone resection of the tongue and floor of the mouth with pectoralis major flap reconstruction.

Clinical reliability of radial forearm free flap in repair of buccal defects.

BACKGROUND: The ideal method for buccal defects should provide good outcome of both function and appearance; our goal is to highlight the reliability of radial forearm flap in buccal reconstruction. METHODS: A retrospective study was conducted. From 2005 to 2012, 20 radial forearm flaps were used to repair the defects. We analyzed the superiority and reliability of the flap; in addition, we reviewed some related literature and made a comparison between radial forearm flap and platysma flap. RESULTS: All radial forearm flaps totally survived, but two flaps suffered venous obstruction, hematoma, respectively. Radial forearm flap preserved the original interincisal distance well. In our follow-up, all patients had sufficient mouth-opening width (mean: 4.3 cm). CONCLUSION: Radial forearm flap is a reliable method for buccal defect reconstruction.

Vertical platysma myocutaneous flap that sacrifices the facial artery and vein.

BACKGROUND: Platysma myocutaneous flap (PMF) is a generally used technique for defect reconstruction after an oral cancer resection. The aim of the study is to present our experience using vertical PMF that sacrificed the facial artery and vein for intraoral reconstruction. METHODS: A retrospective review of the medical records of 54 patients who underwent vertical PMF that sacrificed the facial artery and vein for intraoral reconstruction was performed. A comparison between PMF that sacrificed and that preserved the facial vessels was made, and we also compared PMF that sacrificed the facial vessels with radial forearm free flap (RFFF). Statistics concerning the patients' clinical factors were gathered. RESULTS: The mean age of the 54 patients who underwent PMF that sacrificed the facial artery and vein was 62.0 ± 10.98 years. The co-morbid disease rate of PMF was 53.7%. The flap size ranged from 12 × 5.5 cm to 7 × 5 cm. Survival of the flap was found in all of the cases, with partial necrosis in four cases (7.4%) and total loss in none of the cases. The operation time was 5.7 ± 1.17 h. The complication and success rates were 27.8% and 92.6%, respectively. The 3-year and 5-year survival rates were 77.8% (21/27) and 69.23% (9/13), respectively. The majority of the patients (87.0%) in our series were satisfied with the results of the surgery. There was no significant difference between PMF that sacrificed or that preserved the facial vessels, both in success rate (P = 1) or complication rate (P = 0.72). The patients in the PMF group were older than the patients in the RFFF group (P = 0.011), the operation time was shorter (P < 0.001), and the co-morbid disease rate was higher (P = 0.002). Although the complication rate of PMF (15/54, 27.8%) was higher than that of RFFF (2/34, 5.9%) (P = 0.011), their success rates were similar (92.6%, 94.1%) (P = 1.00). CONCLUSIONS: Vertical PMF that sacrifices the facial artery and vein has specific advantages including in ease preparation and limitations. This technique may provide an effective method for intraoral reconstruction. Our experience in handling the flap may contribute to the success rate.

Comparison studies of different flaps for reconstruction of buccal defects.

Our purpose was to evaluate the feasibility of radial forearm free (RFF) flap, platysma myocutaneous (PM) flap, and anterolateral thigh (ALT) flap in buccal reconstruction. This study consisted of 56 patients who were categorized into 3 groups. The Student t test was used to analyze the variables. Patients in group platysma flap were significantly older, the dissection of platysma flap was easier, and the defect was significantly smaller than those in group radial forearm flap and group ALT flap. The reduction in the widths of mouth opening between group PM, group RFF, and group ALT were compared. However, the reduction of mouth-opening widths in group RFF and group ALT was significantly less than that in group PM. Platysma myocutaneous flap may be more suitable in patients with small to middle-size defect and poor status, although the flap cannot achieve a reliable result; anterolateral thigh flap and radial forearm flap can preserve the interincisal distance well even for large buccal defect, but it takes more time and skills in the operation.

Free fibula flap: assessment of quality of life of patients with head and neck cancer who have had defects reconstructed.

This study investigated the quality of life (QoL) of patients with head and neck cancer undergoing immediate reconstruction of the mandible with free fibula flap. From March 2006 to January 2011, the QoL of 42 patients was assessed using the Medical Outcomes Study Short Form 36 and the University of Washington QoL (version 4) questionnaires. The assessments were performed at least 24 months after surgery. A total of 31 of the 42 questionnaires (73.8%) were returned. The length of harvested fibula varied from 17.5 to 26.1 cm. In the Short Form 36, the lowest-scoring domain was vitality, whereas the highest scores occurred in physical role. According to the University of Washington QoL, the key domains affected by surgery are chewing, speech, and appearance. The domain of pain has the best score. There was a significant effect on the QoL of patients with head and neck cancer with resections of the mandible who had undergone free fibula flap reconstruction. Data from this study may provide useful information for physicians and patients, which may be of value during discussion of treatment modalities for head and neck cancers.

Quality of life in patients younger than 40 years treated for anterior tongue squamous cell carcinoma.

This study investigated the quality of life in patients younger than 40 years with tongue squamous cell carcinoma. We used the University of Washington Head and Neck Quality of Life scale to compare the quality of life outcomes between young and old patients. Cases were patients younger than 40 years who were treated for anterior tongue squamous cell carcinoma. Controls were patients older than 40 years who were matched to the cases regarding diagnosis, sex, and TNM classification. Two controls were matched for each case; thus, 21 cases and 42 controls were selected. Twenty-one of 33 questionnaires (63.6%) were returned. The median follow-up duration was 3.7 years (range, 1-12 y). In the group of young patients, the best-scoring domains were pain, chewing, and swallowing, whereas the lowest scores were for appearance, mood, and anxiety. Young patients (40 years or younger) reported better function, notably regarding activity, recreation, shoulder, taste, and saliva compared with the old patients with anterior tongue squamous cell carcinoma. The patients younger than 40 years tend to have a good quality of life. Most of them were not significantly affected by pain. Quality of life should be used as part of our treatment of anterior tongue squamous cell carcinoma.

Mitigating the impact of outliers in traffic crash analysis: A robust Bayesian regression approach with application to tunnel crash data.

Traffic crash datasets are often marred by the presence of anomalous data points, commonly referred to as outliers. These outliers can have a profound impact on the results obtained through the application of traditional methods such as logit and probit models, commonly used in the domain of traffic safety analysis, resulting in biased and unreliable estimates. To mitigate this issue, this study introduces a robust Bayesian regression approach, the robit model, which utilizes a heavy-tailed Student's t distribution to replace the link function of these thin-tailed distributions, effectively reducing the influence of outliers on the analysis. Furthermore, a sandwich algorithm based on data augmentation is proposed to enhance the estimation efficiency of posteriors. The proposed model is rigorously tested using a dataset of tunnel crashes, and the results demonstrate its efficiency, robustness, and superior performance compared to traditional methods. The study also reveals that several factors such as night and speeding have a significant impact on the injury severity of tunnel crashes. This research provides a comprehensive understanding of the outliers treatment methods in traffic safety studies and offers valuable recommendations for the development of appropriate countermeasures to effectively prevent severe injuries in tunnel crashes.

A predictable prospect of the South Asian summer monsoon.

Prediction of the South Asian summer monsoon (SASM) has remained a challenge for both scientific research and operational climate prediction for decades. By identifying two dominant modes of the SASM, here we show that the unsatisfactory prediction may be due to the fact that the existing SASM indices are mostly related to the less predictable second mode. The first mode, in fact, is highly predictable. It is physically linked to the variation of the Indian monsoon trough coupled with large rainfall anomalies over core monsoon zone and the northern Bay of Bengal. An index is constructed as a physical proxy of this first mode, which can be well predicted one season in advance, with an overall skill of 0.698 for 1979-2020. This result suggests a predictable prospect of the SASM, and we recommend the new index for real-time monitoring and prediction of the SASM.

Impact of different types of entrepreneurial alertness on entrepreneurial opportunities identification.

In the context of resource constraints, how different dimensions of entrepreneurial alertness affect the entrepreneurial opportunity recognition of new ventures is an important issue worth studying. From entrepreneurial cognition theory and bricolage theory perspectives, we systematically investigate the intrinsic relationships among entrepreneurial alertness, entrepreneurial bricolage, entrepreneurial passion, and entrepreneurial opportunity recognition. Further, it explored the intrinsic mechanism of role in exploring entrepreneurial opportunity recognition. This study applied stepwise regression analyses and the Bootstrap method to test the hypotheses on a sample of 295 questionnaires of the new venture. The findings revealed that entrepreneurial alertness is positively related to entrepreneurial opportunity recognition. Entrepreneurial bricolage is positively related to entrepreneurial opportunity recognition. Entrepreneurial bricolage partially mediates between entrepreneurial alertness and entrepreneurial opportunity recognition. Entrepreneurial passion positively moderates the relationship between entrepreneurial bricolage and entrepreneurial opportunity identification. The study guides new ventures to enhance entrepreneurial alertness and reasonably use entrepreneurial bricolage to explore entrepreneurial opportunities.

Core immune cell infiltration signatures identify molecular subtypes and promote precise checkpoint immunotherapy in cutaneous melanoma.

Yutao Wang, China Medical University, ChinaThe tumor microenvironment (TME) has been shown to impact the prognosis of tumors in patients including cutaneous melanoma (CM); however, not all components of TME are important. Given the aforementioned situation, the functional immune cell contents correlated with CM patient prognosis are needed to optimize present predictive models and reflect the overall situation of TME. We developed a novel risk score named core tumor-infiltrating immune cell score (cTICscore), which showed certain advantages over existing biomarkers or TME-related signatures in predicting the prognosis of CM patients. Furthermore, we explored a new gene signature named cTILscore-related module gene score (cTMGs), based on four identified TME-associated genes (GCH1, GZMA, PSMB8, and PLAAT4) showing a close correlation with the cTICscore, which was generated by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis to facilitate clinical application. Patients with low cTMGs had significantly better overall survival (OS, P = 0.002,< 0.001, = 0.002, and = 0.03, respectively) in the training and validating CM datasets. In addition, the area under the curve values used to predict the immune response in four CM cohorts were 0.723, 0.723, 0.754, and 0.792, respectively, and that in one gastric cohort was 0.764. Therefore, the four-gene signature, based on cTICscore, might improve prognostic information, serving as a predictive tool for CM patients receiving immunotherapy.cutaneous melanoma, tumor microenvironment, prognosis, immunotherapy, cTICscore.