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Objective: Interferon (IFN)‐1 signatures are a hallmark of patients with systemic sclerosis (SSc). However, its significance in clinical stratification and contribution to deterioration still need to be better understood. Methods: For hypothesis generation, we performed single‐cell RNA sequencing (scRNA‐seq) on skin biopsies (four patients with SSc and two controls) using the BD Rhapsody platform. Two publicly available data sets of skin scRNA‐seq were used for validation (GSE138669: 12 patients with diffuse cutaneous SSc [dcSSc] and 10 controls; GSE195452: 52 patients with dcSSc and 41 patients with limited cutaneous SSc [lcSSc] and 54 controls). The IFN‐1 signature was mapped, functionally investigated in a bleomycin plus IFNα‐2 adenovirus‐associated virus (AAV)–induced model and verified in an SSc cohort (n = 61). Results: The discovery and validation data sets showed similar findings. Endothelial cells (ECs) had the most prominent IFN‐1 signature among dermal nonimmune cells. The EC IFN‐1 signature was increased both in patients with SSc versus controls and in patients with dcSSc versus those with lcSSc. Among EC subclusters, the IFN‐1 signature was statistically higher in the capillary ECs of patients with dcSSc, which was higher than those in patients with lcSSc, which in turn was higher than those in healthy controls (HCs). Endothelial‐to‐mesenchymal transition (EndoMT) scores increased in parallel. Deteriorated bleomycin‐induced dermal fibrosis, EndoMT, and perivascular fibrosis and caused blood vessel loss with EC apoptosis. Vascular myxovirus resistance (MX) 1, an IFN‐1 response protein, was significantly increased both in total SSc versus HC skin and in dcSSc versus lcSSc skin. Baseline vascular MX1 performed similarly to skin score in predicting disease progression over 6 to 34 months in total SSc and was superior in the dcSSc subpopulation. Conclusion: The EC IFN‐1 signature distinguished SSc skin subtypes and disease progression and may contribute to vasculopathy and fibrosis. [ABSTRACT FROM AUTHOR]

CD73 plays a critical role in the pathogenesis and immune escape in pancreatic ductal adenocarcinoma (PDAC). AB680, an exceptionally potent and selective inhibitor of CD73, is administered in an early clinical trial, in conjunction with gemcitabine and anti‐PD‐1 therapy, for the treatment of PDAC. Nevertheless, the specific therapeutic efficacy and immunoregulation within the microenvironment of AB680 monotherapy in PDAC have yet to be fully elucidated. In this study, AB680 exhibits a significant effect in augmenting the infiltration of responsive CD8+ T cells and prolongs the survival in both subcutaneous and orthotopic murine PDAC models. In parallel, it also facilitates chemotaxis of myeloid‐derived suppressor cells (MDSCs) by tumor‐derived CXCL5 in an AMP‐dependent manner, which may potentially contribute to enhanced immunosuppression. The concurrent administration of AB680 and PD‐1 blockade, rather than gemcitabine, synergistically restrain tumor growth. Notably, gemcitabine weakened the efficacy of AB680, which is dependent on CD8+ T cells. Finally, the supplementation of a CXCR2 inhibitor is validated to further enhance the therapeutic efficacy when combined with AB680 plus PD‐1 inhibitor. These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC. [ABSTRACT FROM AUTHOR]

Multicentric reticulohistiocytosis (MRH) is a rare systemic disorder characterized by inflammatory histiocytic infiltrates, mainly affecting the synovium, skin, and subcutaneous tissues. More patients are needed to confirm the effectiveness of JAKi treatment; but we suggest JAKi as a promising treatment option for MRH, especially when conventional drugs have failed. Additionally, CD1a and S100 stains are negative, indicating that the histiocytes are not Langerhans cells.[2] As the etiology and pathogenesis of MRH remain unknown, treatment of MRH remains largely empirical. It is more commonly observed in women (female:male ratio of 3:1) with mean presentation age between 40 and 50 years old.[2] Arthropathy is often rapidly progressive and can lead to destructive arthritis in 50% of MRH cases and flexion deformities in 14%.[[2]] Distal interphalangeal joints are the most frequently involved, and are one of the defining characteristics of MRH. [Extracted from the article]

Background: Intraductal papillary mucinous neoplasms (IPMNs) are the precursor lesions of pancreatic cancers, requiring active surgical intervention during cancer development. However, the current criteria for predicting malignant IPMNs remain challenging and limited. Hence, this study aimed to assess the discriminatory performance of circulating cytokines, including TNF‐α, IL‐2R, IL‐6, and IL‐8, then build a novel predictive model to improve the diagnostic accuracy. Method: A total of 131 retrospective (from March 2016 to December 2019) and 53 prospective (from March 2020 to January 2021) patients who were histologically confirmed as IPMNs were consecutively collected and analyzed. Result: The circulating levels of TNF‐α, IL‐2R, IL‐6, and IL‐8 were significantly elevated in malignant IPMNs, and were verified as independent factors for malignant IPMNs (p < 0.05). Then, a novel score, the circulating cytokine score (CCS), was calculated and demonstrated as an independent predictive indicator with a higher area under the curve (AUC) than each cytokine alone (p < 0.001). Besides the CCS, two high‐risk stigmata features, the presence of solid component (PSC), and main pancreatic duct (MPD) dilation ≥10 mm were also demonstrated as independent indicators for predicting malignant IPMNs. Finally, a novel nomogram incorporating the CCS and these two high‐risk stigmata features presented a remarkable diagnostic performance, both in the training and validation cohorts with AUCs of 0.928 and 0.873, respectively. Conclusion: The CCS can be considered a novel independent predictive indicator for malignant IPMNs. Additionally, the formulated nomogram model integrating the CCS, PSC, and MPD ≥10 mm can be a valuable and promising tool for predicting the malignant transformation of IPMNs during long‐term follow‐ups to assist in timely and accurate surgical decisions. [ABSTRACT FROM AUTHOR]

The Sanya incoherent scatter radar (SYISR) is a newly built active digital phased array, all solid‐state transmitting and digital receiving incoherent scatter radar in Sanya (18.3°N, 109.6°E). The radar frequency band is from 430 to 450 MHz. The Sanya site is a low latitude station in China dedicated for ionospheric investigation. Meanwhile, SYISR is also suitable for detecting a wide range of space debris because of its high power and flexible beam steering ability. In this paper, we first calculate the detectable lower limit size of space debris with respect to integration time and range based on SYISR parameters through theoretical simulation. Then, we selected several typical space debris, with a size near the theoretical detectable lower limit, to perform the experiment. We found that the estimated radar cross section versus range accorded well with the theoretical curve, which confirmed our simulation. Specifically, the detectable lower limit size of space debris is ∼8 cm in a range of 1,000 km given a threshold signal‐to‐noise ratio of 14 dB. This value decreases to ∼3 cm if a 200‐ms coherent integration is implemented. We further performed several experiments on objects with different inclinations using signals with 0.3 and 4 MHz under both static staring and tracking modes. In comparison with the two‐line element file predicted raw orbit, the tracking error of 0.3 and 4 MHz are 7 km and 400 m, respectively, without coherent integration in the processing. The study expands the function of the SYISR and should be beneficial to our ionospheric data inversion given the frequent occurrence of space debris around the SYISR. Key Points: Simulation and experiments to evaluate space debris detection performance based on newly built Sanya incoherent scatter radar (SYISR) have been performedThe estimated radar cross section versus range of typical space debris accord well with the theoretical curveThe detectable lower limit size of space debris is ∼8 cm in a range of 1,000 km without integration based on SYISR [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most aggressive diseases in the world due to a lack of early detection, leading to an overall 5‐year survival of only 10%. In recent years, clinical trials targeted pancreatic cancer in efforts to improve survival. These studies introduce new technologies, concepts, and evidence which have instilled new optimism for improving prognosis. This review summarizes the current status of the recent (5‐year) clinical trials and describes contemporary research on pancreatic cancer, including surgical technology, diagnostic skills, traditional chemoradiotherapy, neoadjuvant chemotherapy, immunotherapy, targeted therapy, and precision medicine. Then, the future trend and direction of clinical trials on pancreatic cancer are discussed. [ABSTRACT FROM AUTHOR]

This article discusses a case of Bier spots, which are transient anemic macules that develop on the extremities. The patient, an Asian woman in her 30s, presented with multiple white spots on her palms and soles, which appeared after she had been diagnosed with COVID-19 three months earlier. The article suggests that Bier spots may be a result of post-COVID endothelial dysfunction. The patient was prescribed vasodilators, but no improvement was observed, and the symptoms disappeared gradually after six months. The article emphasizes the importance of early recognition of Bier spots as a dermatologic manifestation associated with COVID-19 to avoid overtreatment. [Extracted from the article]

CD73 is a glycosylphosphatidylinositol (GPI)‐anchored protein that attenuates tumour immunity via cooperating with CD39 to generate immunosuppressive adenosine. Therefore, CD73 blockade has been incorporated into clinical trials for cancers based on preclinical efficacy. However, the biological role and underlying mechanism of CD73 in pancreatic cancer (PC) microenvironment and its prognostic impact have not been comprehensively studied. In this article, we found that the expression of CD73 was up‐regulated in PC tissues and patients with higher CD73 expression had poorer overall survival (OS) and disease‐free survival (DFS) in multiple publicly available databases. Higher CD73 expression was significantly associated with its reduced methylation, and only the hypomethylation of CpG site at cg23172664 was obviously correlated with poorer OS. Then, Metascape analysis and GSEA showed that CD73 may play an important role in PC progression and immune regulations. Notably, CD73 was verified to be negatively correlated with infiltrating levels of CD8+ T cells and γδ+ T cells in both TCGA and GEO cohorts via the CIBERSORT algorithm. In addition, patients with higher CD73 expression also tended to have higher PD‐L1 expression and tumour mutation load. It seemed that CD73 might be a promising biomarker for the response to the anti‐PD‐1/PD‐L1 treatment in PC. In conclusion, these results reveal that CD73 may function as a promotor in cancer progression and a regulator in immune patterns via CD73‐related pathways. Blockade of CD73 might be a promising therapeutic strategy for PC. [ABSTRACT FROM AUTHOR]