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Abstract This study aimed to evaluate the safety and efficacy of camrelizumab combined with chemotherapy during preoperative neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) of clinical Stages II and III. The patients received camrelizumab plus chemotherapy regimen on Day 1 for up to three to four cycles (3 weeks per cycle). The probabilities of overall survival (OS) were 55.6% at 12 months and 35.6% at 18 months (45 patients). The disease‐free survival (DFS) rates were 70.0% at 12 months and 63.3% at 18 months (30 patients). The median OS and DFS were not reached. The proportion of patients at postneoadjuvant pathological tumor stages ypT0, ypT2, and ypT3 were 10 (33.3%), 14 (46.7%), and 6 (20.0%), respectively, and those at stages ypN0 and ypN1 were 19 (63.3%) and 11 (36.7%), respectively. Additionally, the pathological complete response rate was 33.3% (95% confidence interval [CI]: 0.154–0.512), and the major pathologic response rate was 46.7% (95% CI: 0.277–0.656). Grade ≥3 adverse events (AEs) were reported in five patients (11.1%), with vomiting being the most common AE (three patients; 3.3%). Other common AEs of any grade included decreased lymphocyte count (48.9%), reactive capillary endothelial proliferation (46.7%), decreased white blood cell count (40.0%), anemia (31.1%), and vomiting (31.1%). The combination of camrelizumab and neoadjuvant chemotherapy in patients with locally advanced resectable ESCC demonstrated promising efficacy and acceptable safety.

The interleukin 1 (IL-1) receptor family, whose members contain three immunoglobulin-like domains (D1-D3) in the extracellular region, is responsible for transmitting pleiotropic signals of IL-1 cytokines. The inter-domain flexibility of IL-1 receptors and its functional roles have not been fully elucidated. In this study, we used small-angle X-ray scattering to show that ligand-binding primary receptors and co-receptors in the family all have inherent inter-domain flexibility due to the D2/D3 linker. Variants of the IL-1RAcP and IL-18Rβ co-receptors with mutated D2/D3 linkers cannot form a cytokine-receptor complex and mediate signaling. Our analysis further revealed that these mutated co-receptors exhibited a changed conformational ensemble, suggesting that loss of function is due to the alteration of receptor dynamics. Taken together, our results demonstrate that the D2/D3 linker is a critical functional determinant of IL-1 receptor and underscore the important roles of the inter-domain flexibility in cytokine/receptor binding and signaling.

Background: Psoriatic arthritis (PSA) is an inflammatory joint disease associated with psoriasis (PSO) that can be easily missed. Existing PSA screening tools ignore objective serologic indicators. The aim of this study was to develop a disease screening model and the Psoriatic Arthritis Inflammation Index (PSAII) based on serologic data to enhance the efficiency of PSA screening. Method: A total of 719 PSO and PSA patients from the National Health and Nutrition Examination Survey (NHANES) (as training set and test set) and 135 PSO and PSA patients who were seen at The First Affiliated Hospital of Zhejiang Chinese Medical University (as external validation set) were selected, 31 indicators for these patients were collected as potential input features for the model. Least Absolute Shrinkage and Selection Operator (LASSO) was used to identify PSA-related features. Five models of logistic regression (LR), random forest, k-nearest neighbor, gradient augmentation and neural network were developed in the training set using quintuple cross validation. And we developed PSAII based on the results of LASSO regression and weights of logistic model parameters. All performance metrics are derived on the test set and the external validation set. Results: Five variables were selected to build models, including age, lymphocyte percentage, neutrophil count, eosinophilic count, and C-reactive protein. In all established models, the LR model performed the best, with an Area Under Curve (AUC) of 0.87 (95% confidence interval (CI): 0.83-0.90) on the test set; on the external validation set the AUC was 0.82 (95%CI: 0.74-0.90). The PSAII formula was PSAII = percentage of lymphocytes × C-reactive protein/(neutrophil count × eosinophilic count × 10). The AUC of PSAII in the test is 0.93 (95%CI: 0.88-0.97), and the cutoff value is 18. The AUC of the external validation set is 0.81 (95%CI: 0.72-0.89). Conclusions: This study developed and validated five models to assist screening for PSA by analyzing serum data from NHANES and Chinese populations. The LR model demonstrated the best performance. We created PSAII for PSA screening. However, the high false positive rate of PSAII makes it necessary to combine it with other PSA screening tools when applied. [ABSTRACT FROM AUTHOR]

The past two decades have seen widespread efforts being directed toward the development of nanoscale lasers. A plethora of studies on single such emitters have helped demonstrate their advantageous characteristics such as ultrasmall footprints, low power consumption, and room-temperature operation. Leveraging knowledge about single nanolasers, the next phase of nanolaser technology will be geared toward scaling up design to form arrays for important applications. In this review, we discuss recent progress on the development of such array architectures of nanolasers. We focus on valuable attributes and phenomena realized due to unique array designs that may help enable real-world, practical applications. Arrays consisting of exactly two nanolasers are first introduced since they can serve as a building block toward comprehending the behavior of larger lattices. These larger-sized lattices can be distinguished depending on whether or not their constituent elements are coupled to one another in some form. While uncoupled arrays are suitable for applications such as imaging, biosensing, and even cryptography, coupling in arrays allows control over many aspects of the emission behavior such as beam directionality, mode switching, and orbital angular momentum. We conclude by discussing some important future directions involving nanolaser arrays.