Long-term immunogenicity and safety of heterologous boosting with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants who had received two or three doses of inactivated vaccine.

The emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs booster vaccination. We evaluated the long-term safety and immunogenicity of heterologous boosting with a SARS-CoV-2 messenger RNA vaccine SYS6006. A total of 1000 participants aged 18 years or more who had received two (Group A) or three (Group B) doses of SARS-CoV-2 inactivated vaccine were enrolled and vaccinated with one dose of SYS6006 which was designed based on the prototype spike protein and introduced mutation sites. Adverse events (AEs) through 30 days and serious AEs during the study were collected. Live-virus and pseudovirus neutralizing antibody (Nab), binding antibody (immunoglobulin G [IgG]) and cellular immunity were tested through 180 days. Solicited all, injection-site and systemic AEs were reported by 618 (61.8%), 498 (49.8%), and 386 (38.6%) participants, respectively. Most AEs were grade 1. The two groups had similar safety profile. No vaccination-related SAEs were reported. Robust wild-type (WT) live-virus Nab response was elicited with peak geometric mean titers (GMTs) of 3769.5 (Group A) and 5994.7 (Group B) on day 14, corresponding to 1602.5- and 290.8-fold increase versus baseline, respectively. The BA.5 live-virus Nab GMTs were 87.7 (Group A) and 93.2 (Group B) on day 14. All participants seroconverted for WT live-virus Nab. Robust pseudovirus Nab and IgG responses to wild type and BA.5 were also elicited. ELISpot assay showed robust cellular immune response, which was not obviously affected by virus variation. In conclusion, SYS6006 heterologous boosting demonstrated long-term good safety and immunogenicity in participants who had received two or three doses of SARS-CoV-2 inactivated vaccine.

Safety and immunogenicity of heterologous boosting with a bivalent SARS-CoV-2 mRNA vaccine (XBB.1.5/BQ.1) in Chinese participants aged 18 years or more: A randomised, double-blinded, active-controlled phase 1 trial.

Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants urges the development of new vaccines. We assessed the safety and immunogenicity of SYS6006.32, a bivalent vaccine (XBB.1.5/BQ.1), in healthy adults who had received SARS-CoV-2 primary vaccination. In a randomised, double-blinded, active-controlled trial, 200 participants were randomised to receive one dose of SYS6006.32 (N = 100) or a prototype-based, monovalent control vaccine SYS6006 (N = 100). Adverse events (AEs) were collected through the study. Immunogenicity was assessed by live-virus neutralising antibody (Nab) and pseudovirus Nab. 61 (61.0 %) and 60 (60.0 %) participants reported AE in the SYS6006.32 and SYS6006 groups, respectively. Most AEs were grade 1 or 2. Pain and fever were the most common injection-site and systemic AEs, respectively. No serious AEs were observed. SYS6006.32 heterologous boosting induced robust Nab responses against BA.5, XBB.1.5 and EG.5 with live-virus Nab geometric mean titres (GMTs) increased by 17.1-, 34.0-, and 48.0-fold, and pseudovirus Nab GMTs increased by 12.2-, 32.0-, and 35.1-fold, respectively, 14 days after vaccination. SYS6006.32 demonstrated a superior immunogenicity to SYS6006. SYS6006.32 also induced robust pseudovirus Nab responses against XBB.1.16, XBB.2.3, and BA.2.86, with GMTs 3- to 6-fold higher than those induced by SYS6006. In conclusion, SYS6006.32 showed good safety profile and superior immunogenicity to the monovalent vaccine SYS6006.

100-Phones: A Large VI-SLAM Dataset for Augmented Reality Towards Mass Deployment on Mobile Phones.

Visual-inertial SLAM (VI-SLAM) is a key technology for Augmented Reality (AR), which allows the AR device to recover its 6-DoF motion in real-time in order to render the virtual content with the corresponding pose. Nowadays, smartphones are still the mainstream devices for ordinary users to experience AR. However the current VI-SLAM methods, although performing well on high-end phones, still face robustness challenges when deployed on a larger stock of mid- and low-end phones. Existing VI-SLAM datasets use either very ideal sensors or only a limited number of devices for data collection, which cannot reflect the capability gaps that VI-SLAM methods need to solve when deployed on a large variety of phone models. This work proposes 100-Phones. the first VI-SLAM dataset covering a wide range of mainstream phones in the market. The dataset consists of 350 sequences collected by 100 different models of phones. Through analysis and experiments on the collected data, we conclude that the quality of visual-inertial data vary greatly among the mainstream phones, and the current open source VI-SLAM methods still have serious robustness issues when it comes to mass deployment on mobile phones. We release the dataset to facilitate the robustness improvement of VI-SLAM and to promote the mass popularization of AR. Project page: https://github.com/zju3dv/100-Phones.

Oral mucosal changes in tight junction proteins in patients with oral lichen planus.

OBJECTIVE: This study aimed to investigate the expression of tight junction, its distribution pattern in oral lichen planus samples and its potential association with the severity of oral lichen planus. MATERIALS AND METHODS: Cross-sectional study designs were conducted. Transcriptome sequencing was conducted using oral mucosal tissues from 22 patients with oral lichen planus and 11 healthy controls. Immunohistochemistry and quantitative reverse transcription PCR were performed to verify the expression of claudin-1, claudin-4, occludin and zonula occludens-1 in oral mucosal tissues from another 30 patients with oral lichen planus and 26 healthy controls. The relationship between tight junction protein expression and oral lichen planus severity was explored using correlation analysis. RESULTS: 5603 and 2475 differentially expressed genes were upregulated and downregulated respectively, in oral lichen planus tissues. KEGG analysis showed that tight junctions including CLDN1, CLDN4, OCLN and TJP1 were downregulated in oral lichen planus. Claudin-1, claudin-4, occludin and zonula occludens-1 expression was verified to be significantly lower in oral lichen planus. Furthermore, correlation analyses showed that decreased occludin expression was positively related to oral lichen planus severity. CONCLUSION: Decreased expression of TJ barrier proteins may be associated with the development of oral lichen planus.

[Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through transcriptome sequencing].

OBJECTIVE: To detect key genes of local glucocorticoid therapy in oral lichen planus (OLP) through transcriptome sequencing. METHODS: The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa, Peking University Hospital of Stomatology from November 2019 to March 2023. Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min, 3 times daily for 4 weeks. The patients' signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome. Their mucosa samples were collected before treatment. After isolating total RNA, transcriptome sequencing was performed. The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software, and the Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes (DEGs), accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone. RESULTS: After 4 weeks treatment by topical dexamethasone, 13 cases of the 28 OLP patients responding well with the sign score reducing from 7.0 (4.5, 9.0) to 5.0 (3.0, 6.3), pain score decreasing from 5.0 (2.0, 5.5) to 2.0 (0.0, 3.5), oral health impact profile lessening from 5.0 (3.5, 9.0) to 1.0 (0.0, 5.0) significantly (P<0.01) were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group. There were no significant differences of demographic and baseline levels of clinical features, especially disease severity between these two groups. A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between effective group and ineffective group. KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8, CTNNA3, MYL2 and MYLPF were associated with leukocyte transendothelial migration, while downregulated genes were significantly enriched in tumor necrosis factor (TNF), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB) signaling pathways, and cortisol synthesis and secretory. CONCLUSION: High expressions of CLDN8, CTNNA3, MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone, while patients with high expression genes of inflammation pathway such as TNF, IL-17, NF-κB and cortisol synthesis and secretion received poor effect.

Examining the relationship between nutritional status and wound healing in head and neck cancer treatment: A focus on malnutrition and nutrient deficiencies.

The research was conducted to examine the correlation between nutritional status and wound healing in individuals who were receiving treatment for head and neck cancer. Specifically, this study sought to identify crucial nutritional factors that influenced both the recovery process and efficacy of the treatment. From February 2022 to September 2023, this cross-sectional study was undertaken involving 300 patients diagnosed with head and neck cancer who were treated at Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. In order to evaluate nutritional status, body mass index (BMI), serum protein levels and dietary intake records were utilized. The assessment of wound healing was conducted using established oncological wound healing scales, photographic documentation and clinical examinations. After treatment, we observed a noteworthy reduction in both BMI (p < 0.05) and serum albumin levels (p < 0.05). There was slightly increased prevalence of head and neck cancer among males (61.0%, p < 0.05). Over the course of 6 months, significant enhancement in wound healing scores was noted, exhibiting overall improvement of 86% in the healing process. An inverse correlation was identified between nutritional status and wound healing efficacy through multivariate analysis. A logistic regression analysis revealed a significant positive correlation (p < 0.05) between elevated levels of serum protein and total lymphocytes and enhanced wound healing. Conversely, negative correlation (p < 0.05) was observed between larger wound size at baseline and healing. The research findings indicated noteworthy association between malnutrition and impaired wound repair among individuals diagnosed with head and neck cancer. The results underscored the significance of integrating nutritional interventions into therapeutic protocol in order to enhance clinical results. This research study provided significant contributions to the knowledge of intricate nature of head and neck cancer management by advocating for multidisciplinary approach that incorporates nutrition as the critical element of patient care and highlighted the importance of ongoing surveillance and customized dietary approaches in order to optimize wound healing and treatment efficacy.

Immunogenicity and safety of a SARS-CoV-2 mRNA vaccine (SYS6006) in healthy Chinese participants: A randomized, observer-blinded, placebo-controlled phase 2 clinical trial.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine enables quick upgrade of antigen sequence to combat emerging new variants. In an observer-blinded, randomized, placebo-controlled phase 2 trial, immunologically naïve 300 adults and 150 older participants were enrolled and randomized (1:1:1) to receive two doses of 20 µg or 30 µg of a SARS-CoV-2 mRNA vaccine (SYS6006) or placebo. Adverse events (AEs) were recorded through 30 days after the second dose. Live virus neutralizing antibody (Nab), S1 protein-specific binding antibody (S1-IgG) and cellular immunity were tested. Results showed that robust wild-type Nab response was elicited with geometric mean titers of 91.3 and 84.9 in the adults, and 74.0 and 115.9 in the elders, 14 days following the second dose (Day 35) in the 20-µg and 30-µg groups, respectively. All seroconverted for wild-type Nab except two participants. Nab against Omicron BA.5 was mild. Robust wild-type S1-IgG response was induced with geometric mean concentrations of 2751.0 and 3142.2 BAU/mL in adults, and 2474.1 and 2993.5 BAU/mL in elders at Day 35 in the 20-µg and 30-µg groups, respectively. S1-IgG against Omicron BA.2 was induced. Cellular immunity was elicited, particularly in enzyme-linked immunospot assay. The most frequent AEs were injection-site pain and fever. Most reported AEs were grade 1 or grade 2. The AE incidences were similar following the first dose and second dose. No vaccination-associated serious AE was reported. In conclusion, two-dose vaccination with SYS6006 demonstrated good safety, tolerability and immunogenicity in immunologically naïve healthy participants aged 18 years or more.

Development of Antibacterial Peptides with Membrane Disruption and Folate Pathway Inhibitory Activities against Methicillin-Resistant Staphylococcus aureus.

Antimicrobial peptides (AMPs) offer an opportunity to overcome multidrug resistance. Here, novel peptides were designed based on AMP fragments derived from sea cucumber hemolytic lectin to enhance anti-methicillin-resistant Staphylococcus aureus (MRSA) activity with less side effects. Two designed peptides, CGS19 (LARVARRVIRFIRRAW-NH2) and CGS20 (RRRLARRLIFFIRRAW-NH2), exhibited strong antibacterial activities against clinically isolated MRSA with MICs of 3-6 µM, but no obvious cytotoxicity was observed. Consistently, CGS19 and CGS20 exerted rapid bactericidal activity and effectively induced 5.9 and 5.8 log reduction of MRSA counts in mouse subeschar, respectively. Further, CGS19 and CGS20 kill bacteria not only through disturbing membrane integrity but also by binding formate-tetrahydrofolate ligase, a key enzyme in the folate metabolism pathway, thereby inhibiting the folate pathway of MRSA. CGS19 and CGS20 are promising lead candidates for drug development against MRSA infection. The dual mechanisms on the identical peptide sequence or scaffold might be an underappreciated manner of treating life-threatening pathogens.

Preclinical Study on a Novel Fluoroderivative of Dabigatran Etexilate in Animal Models.

ABSTRACT: Here, the fluorinated derivative, R1, was synthesized from the fluorinated dabigatran derivative (R0). The in vivo pharmacokinetic characteristics of orally administered R1, R0 injection, and dabigatran etexilate in rats were compared. Safety evaluation results showed no significant changes in the QRS wave or PR and QT intervals in rat lead II electrocardiograms. The possible toxicity of R1 was studied using the limit test method, and no obvious toxicity occurred in mice after the acute oral administration of R1. R1 inhibited thrombin-induced platelet aggregation in a dose-dependent manner, had an inhibitory effect on platelet aggregation induced by arachidonic acid and adenosine diphosphate, could significantly prolong prothrombin time and activated partial thromboplastin time, and increased fibrinogen levels. R1 is the optimal candidate compound from among more than 100 candidate compounds designed and synthesized by our research group. It was first selected through preliminary in vitro anticoagulant activity screening and further through in vivo mouse activity testing. A systematic pharmacodynamic study showed that R1 was superior to the raw material drug dabigatran ester; particularly, the absolute bioavailability of R1 increased by 206%, and this can overcome the low bioavailability defect associated with the marketed drug dabigatran ester. Another safety assessment of R1 indicated that there were no risks of acute poisoning in rats and cardiac toxicity in mice or rats. Therefore, R1 can be considered a new candidate anticoagulant compound with great potential and significance for further clinical research.

A Unified Particle-Based Solver for Non-Newtonian Behaviors Simulation.

In this article, we present a unified framework to simulate non-Newtonian behaviors. We combine viscous and elasto-plastic stress into a unified particle solver to achieve various non-Newtonian behaviors ranging from fluid-like to solid-like. Our constitutive model is based on a Generalized Maxwell model, which incorporates viscosity, elasticity and plasticity in one non-linear framework by a unified way. On the one hand, taking advantage of the viscous term, we construct a series of strain-rate dependent models for classical non-Newtonian behaviors such as shear-thickening, shear-thinning, Bingham plastic, etc. On the other hand, benefiting from the elasto-plastic model, we empower our framework with the ability to simulate solid-like non-Newtonian behaviors, i.e., visco-elasticity/plasticity. In addition, we enrich our method with a heat diffusion model to make our method flexible in simulating phase change. Through sufficient experiments, we demonstrate a wide range of non-Newtonian behaviors ranging from viscous fluid to deformable objects. We believe this non-Newtonian model will enhance the realism of physically-based animation, which has great potential for computer graphics.

Safety and immunogenicity of primary vaccination with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants aged 18 years or more: Two randomized, observer-blinded, placebo-controlled and dose-escalation phase 1 clinical trials.

Vaccination plays a key role in preventing morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the safety and immunogenicity of a SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine SYS6006. In the two randomized, observer-blinded, placebo-controlled phase 1 trials, 40 adult participants aged 18-59 years and 40 elderly participants aged 60 years or more were randomized to receive two doses of SYS6006 or placebo (saline). Adverse events (AEs) were collected through 30 days post the second vaccination. Immunogenicity was assessed by live-virus neutralizing antibody (Nab), spike protein (S1) binding antibody (S1-IgG), and cellular immunity. The result showed that 7/15, 9/15 and 4/10 adult participants, and 9/15, 8/15 and 4/10 elderly participants reported at least one AE in the 20-µg, 30-µg and placebo groups, respectively. Most AEs were grade 1. Injection-site pain was the most common AE. Two adults and one elder reported fever. No vaccination-related serious AE was reported. SYS6006 elicited wild-type Nab response with a peak geometric mean titer of 232.1 and 130.6 (adults), and 48.7 and 66.7 (elders), in the 20-µg and 30-µg groups, respectively. SYS6006 induced moderate-to-robust Nab response against Delta, and slight Nab response against Omicron BA.2 and BA.5. Robust IgG response against wild type and BA.2 was observed. Cellular immune response was induced. In conclusion, two-dose primary vaccination with SYS6006 demonstrated good safety and immunogenicity during a follow-up period of 51 days in immunologically naive population aged 18 years or more. (Trial registry: Chictr.org.cn ChiCTR2200059103 and ChiCTR2200059104).

Barriers to clinical nurse participation in the internet-based home visiting program: a qualitative study.

BACKGROUND: Home visits are an important part of home care. With increasing demand and the rapid development of information technology, an increasing number of regions are experimenting with the use of information technology in home visits, hoping to meet the needs of more patients through technological interventions. However, most of the current studies have focused on patient health improvement through home visits, neglecting to consider the actual experience of nurses as service providers in participating in Internet-based programs. Thus, the purpose of this research is to explore what is holding nurses back from participating after the Internet has been added to traditional home visiting programs. METHODS: This research was designed with an exploratory-descriptive qualitative analysis method. Semistructured interviews were used to collect information on barriers to nurses' participation in the Internet-based home visiting program. Participants included 16 clinical nurses working in various hospitals in Nanjing, China. The thematic analysis method was used to analyze the information. RESULTS: This research identified three themes and twelve subthemes that hinder clinical nurse engagement in the Internet-based home visiting program. The three themes included multiple barriers to individuals, different service modes, and emerging organizational problems. CONCLUSIONS: As a new form of traditional home visiting program in information society, Internet-based home visiting has many shortcomings in the overall program design and service management specifications. For more patients living at home to receive quality care services, it is necessary to take more effective measures to encourage nurses' participation at three levels: nurse demand, service process, and organizational management.

Characteristics of lactate metabolism phenotype in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, and more effective prognostic markers are needed. Lactic acid has been proved to be an important metabolite involved in cancer development, metastasis, and the tumor microenvironment, affecting the prognosis of patients. The role of lactic acid metabolism regulators (LAMRs) in HCC is still unclear. In this study, we analyzed the status of LAMRs, a gene list containing lactate from Molecular Signatures database, in HCC and consensus clustering was performed based on these LAMRs. Cluster B showed higher infiltrations of immune cells, higher TME scores, and a poorer prognosis. We further constructed a risk score based on DEGs using LASSO and COX regression analysis between two clusters, which could effectively predict the prognosis of TCGA-LIHC patients. The GSE14520 cohort confirmed the result. We also examined the correlation of risk scores with clinical characteristics, genetic mutations, drug sensitivity, immune checkpoint inhibitors(ICIs), and immunotherapy. In conclusion, our findings will facilitate a further understanding of the role of partial lactate metabolism related genes in HCC and suggest a new risk score to predict prognosis.

A preparation method for mRNA-LNPs with improved properties.

The properties of mRNA lipid nanoparticles (mRNA-LNPs), including size, empty particles, morphology, storage stability, and transfection potency, are critically dependent on the preparation methods. Here, a Two-step tangential-flow filtration (TFF) method was successfully employed to improve the properties of mRNA-LNPs during the preparation process. This method involves an additional ethanol removal step prior to the particle fusion process. Notably, this innovative approach has yielded mRNA-LNPs with larger particles, a reduced proportion of empty LNPs, optimized storage stability (at least 6 months at 2-8 °C), improved in vitro transfection efficiency, and minimized distribution in the heart and blood in vivo. In summary, this study represents the implementation of the innovative Two-step TFF method in the preparation of mRNA-LNPs. Our findings indicate substantial enhancements in the properties of our mRNA-LNPs, specifically with regard to the percentage of empty LNPs, stability, transfection efficiency, and in vivo distribution. These improvements have the potential to optimize their industrial applicability and expand their clinical use.

Hydroxychloroquine is effective in oral lichen planus: A multicenter, randomized, controlled trial.

OBJECTIVES: This study was aimed to evaluate the safety and benefit of short-term application of hydroxychloroquine in the management of atrophic/erosive/ulcerative oral lichen planus (OLP). METHODS: This multicenter, randomized, controlled, evaluator-blinded, prospective clinical trial was performed from October 1, 2019, to September 1, 2022. A total of 99 patients were randomized to receive systemic use of hydroxychloroquine (n = 50), or topical use of 0.05% dexamethasone (n = 49) for 4 weeks. The response to both treatment modalities was evaluated according to reticulation, hyperemic, and ulceration (RHU) score and visual analog scale (VAS) score. RESULTS: After 4 weeks of medication, both groups showed substantial reduction in RHU and VAS score (p < 0.05). In hydroxychloroquine group, the average of RHU score was reduced from 10.60 to 7.68 (dropped 27.49%), and the average of VAS score was reduced from 3.74 to 2.47 (dropped 34.09%). There were no differences between the two groups in reduction of RHU score and VAS score (p > 0.05). Single factor analysis found hyperemic area (p = 0.019) and erosive/ulcerative area (p = 0.024) had impacts on drug efficacy of hydroxychloroquine, and logistic regression revealed that no factors (p > 0.05) influenced its efficacy. CONCLUSION: These findings indicate hydroxychloroquine is a safe and effective agent in treating atrophic/erosive/ulcerative OLP.

Potential relationship of dyslipidemia with dietary patterns in oral lichen planus patients-A case-control study.

Background/purpose: Dyslipidemia and a high fat diet may increase the predisposition for accumulating body fat in patients with oral lichen planus (OLP). This study aimed to investigate the risk factors obesity, dietary patterns, and lipid metabolism. Materials and methods: A population-based case-control study was conducted between September 2020 and October 2021, recruiting 275 pairs of OLP cases and controls. Information on lipid profiles, diet frequency and waist circumference were gathered. Principal component and factor analysis were used to analyze the semi-quantitative dietary frequency survey data of patients to extract specific dietary patterns. Results: Univariate analysis showed that total cholesterol, triglycerides, and low-density lipoprotein were significantly higher in the OLP group than the control and other oral mucosal disease groups (P < 0.05, P < 0.001, and P < 0.001, respectively). Compared with the baseline group, obese and overweight patients were more common in the OLP group. Dyslipidemia was more common in the OLP group (68%) compared to the healthy mucosa group (32%; P < 0.001, OR = 4.52, 95% CI = 2.49-8.18). Four dietary patterns were described among the subjects. The traditional prone animal food pattern (OR: 24.81, 95% CI: 6.05-101.71, P < 0.001) and animal food pattern (OR: 28.77, 95% CI: 8.10-102.15, P = 0.001) were associated with an increased risk of OLP. Conclusion: The results indicated that a high-fat diet, dyslipidemia and obesity were strongly linked to disease progression in OLP. A diet high in processed food and fat could increase the risk of OLP.

Roles of IL-33 in the Pathogenesis of Cardiac Disorders.

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family and is believed to play important roles in different diseases by binding to its specific receptor suppression of tumorigenicity 2 (ST2). In the heart, IL-33 is expressed in different cells including cardiomyocytes, fibroblasts, endothelium, and epithelium. Although many studies have been devoted to investigating the effects of IL-33 on heart diseases, its roles in myocardial injuries remain obscure, and thus further studies are mandatory to unravel the underlying molecular mechanisms. We highlighted the current knowledge of the molecular and cellular characteristics of IL-33 and then summarized its major roles in different myocardial injuries, mainly focusing on infection, heart transplantation, coronary atherosclerosis, myocardial infarction, and diabetic cardiomyopathy. This narrative review will summarize current understanding and insights regarding the implications of IL-33 in cardiac diseases and its diagnostic and therapeutic potential for cardiac disease management.

Severe cutaneous adverse reactions associated with immune checkpoint inhibitors therapy and anti-VEGF combination therapy: a real-world study of the FDA adverse event reporting system.

BACKGROUND: Immune checkpoint inhibitors (ICIs) therapy combined with anti-vascular endothelial growth factor (anti-VEGF) regimens showed new hope for cancer patients and considered as future pillar of cancer therapy. However, severe cutaneous adverse reactions (SCARs) in patients with ICIs and anti-VEGF combined therapy raise a serious concern and remain thoroughly assessed in clinics. RESEARCH DESIGN AND METHODS: Data retrieved from the first quarter of 2004 to the third quarter of 2022 in FAERS database underwent disproportionality analysis and Bayesian analysis were utilized to detect and assess the SCAR signals of ICIs and ICIs and anti-VEGF combined therapy for comparison. RESULTS: In total, 854 (1.10%) and 80 (1.06%) reports on SCARs associated with ICIs and a combination of ICIs and anti-VEGF therapy, respectively, were analyzed. Most of SCARs reports were associated with the use of pembrolizumab (36.01%), nivolumab (23.97%) and a combination of ipilimumab and nivolumab (19.71%). A use of atezolizumab and bevacizumab combined therapy (60.00%) caused the most SCARs records out of ICIs and anti-VEGF combined therapies. CONCLUSIONS: Treatment with joint therapy of ICIs and anti-VEGF agents may cause severe cutaneous adverse events. It is vital to identify ICI-related SCARs early, and to manage them appropriately.

An RDL Modeling and Thermo-Mechanical Simulation Method of 2.5D/3D Advanced Package Considering the Layout Impact Based on Machine Learning.

The decreasing-width, increasing-aspect-ratio RDL presents significant challenges to the design for reliability (DFR) of an advanced package. Therefore, this paper proposes an ML-based RDL modeling and simulation method. In the method, RDL was divided into blocks and subdivided into pixels of metal percentage, and the RDL was digitalized as tensors. Then, an ANN-based surrogate model was built and trained using a subset of tensors to predict the equivalent material properties of each block. Lastly, all blocks were transformed into elements for simulations. For validation, line bending simulations were conducted on an RDL, with the reaction force as an accuracy indicator. The results show that neglecting layout impact caused critical errors as the substrate thinned. According to the method, the reaction force error was 2.81% and the layout impact could be accurately considered with 200 × 200 elements. For application, the TCT maximum temperature state simulation was conducted on a CPU chip. The simulation indicated that for an advanced package, the maximum stress was more likely to occur in RDL rather than in bumps; both RDL and bumps were critically impacted by layouts, and RDL stress was also impacted by vias/bumps. The proposed method precisely concerned layout impacts with few resources, presenting an opportunity for efficient improvement.