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Rheumatoid arthritis (RA) is a common chronic, systemic autoimmune disease characterized by erosive arthritis, with a global prevalence of 0.25% to 1.00%, which may ultimately lead to joint deformity and loss of function. Antinuclear antibody (ANA) refers to auto-antibodies that target various components of eukaryotic cells. Although ANA may be frequently detected in RA patients, with a positive rate of 30% to 60%, the significance of ANA in the diagnosis and treatment of RA remains unclear. Nuclear patterns in RA population are dominated by speckled and homogeneous patterns, mainly at low titres. The detection rate of extractable nuclear antibodies is usually lower than that of ANA. The serum levels of rheumatoid factor and anti-cyclic citrullinated peptide antibody in ANA-positive RA patients are much higher than ANA-negative ones, and joint erosion of ANA-positive RA patients had more severe joint erosion on imaging as well. Therefore, ANA is a potential predictor of severe joint injury. ANA-positive RA patients are more likely to have extra-articular manifestations [such as subcutaneous nodules(82% vs 46%), ocular lesions(38% vs 6%), and infections(38% vs 12%)].In terms of RA comorbidities, compared to the ANA negative group, the ANA positive group had higher levels of moderate and severe anemia (16.04% vs 6.9%; 6.6% vs 0.07%), Sjogren's syndrome (19.5% vs 4.1%), and vasculitis (29% vs 7%). In addition, ANA positivity is an independent risk factor for elderly RA patients with carotid intimal thickening (HR=4.089) and adverse pregnancy outcomes in female RA (OR=3.268, P=0.045), respectively. Attention should be paid to high-titre ANA-positive RA patients for preventive measures. In terms of treatment, RA patients who are ANA-positive when given tumour necrosis factor-α inhibitor (TNFi) treatment got much poorer therapeutic response than ANA-negative ones, especially those with high titres were more prone to generating anti-drug antibodies. Increase of ANA titer induced by TNFi is associated with no response to TNFi treatment, thus monitoring the change of ANA may predict the long-term efficacy of TNFi. The most common adverse event of TNFi is drug-induced lupus. Although it has been confirmed that the induction of anti-double-stranded DNA antibodies is associated with poor efficacy of TNFi, large-scale studies are still needed to confirm the correlation between the increase of ANA titer or ocurence of dsDNA antibody and the induction of drug-induced lupus. In conclusion, this paper reviews the research progress on ANA characteristics in RA population, clinical manifestations of ANA-positive RA, and the association between ANA and TNFi prognosis. The potential of ANA as a new biomarker of RA needs to be further studied.

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]

Neutrophils, the most prevalent innate immune cells in humans, have garnered significant attention in recent years due to their involvement in cancer progression. This comprehensive review aimed to elucidate the important roles and underlying mechanisms of neutrophils in cancer from the perspective of their whole life cycle, tracking them from development in the bone marrow to circulation and finally to the tumor microenvironment (TME). Based on an understanding of their heterogeneity, we described the relationship between abnormal neutrophils and clinical manifestations in cancer. Specifically, we explored the function, origin, and polarization of neutrophils within the TME. Furthermore, we also undertook an extensive analysis of the intricate relationship between neutrophils and clinical management, including neutrophil-based clinical treatment strategies. In conclusion, we firmly assert that directing future research endeavors towards comprehending the remarkable heterogeneity exhibited by neutrophils is of paramount importance. [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]

Breast cancer is the most prevalent cancer in the world. Currently, the main treatments for breast cancer are radiotherapy, chemotherapy, targeted therapy and surgery. The treatment measures for breast cancer depend on the molecular subtype. Thus, the exploration of the underlying molecular mechanisms and therapeutic targets for breast cancer remains a hotspot in research. In breast cancer, a high level of expression of DNMTs is highly correlated with poor prognosis, that is, the abnormal methylation of tumor suppressor genes usually promotes tumorigenesis and progression. MiRNAs, as non-coding RNAs, have been identified to play key roles in breast cancer. The aberrant methylation of miRNAs could lead to drug resistance during the aforementioned treatment. Therefore, the regulation of miRNA methylation might serve as a therapeutic target in breast cancer. In this paper, we reviewed studies on the regulatory mechanisms of miRNA and DNA methylation in breast cancer from the last decade, focusing on the promoter region of tumor suppressor miRNAs methylated by DNMTs and the highly expressed oncogenic miRNAs inhibited by DNMTs or activating TETs. [ABSTRACT FROM AUTHOR]

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]

Electrochromic devices are the preferred devices for smart windows because they work independently of uncontrollable environmental factors and rely more on the user's personal feelings to adjust actively. However, in practical applications, the ambient temperature still has an impact on device performance, such as durability, reversibility and switching performance, etc. These technical issues have significantly slowed down the commercialization of electrochromic devices (ECDs). It is necessary to investigate the main reasons for the influence of temperature on the device and make reasonable optimization to enhance the effectiveness of the device and extend its lifetime. In recent years, with the joint efforts of various outstanding research teams, the performance of electrochromic devices has been rapidly improved, with a longer lifetime, richer colors, and better color contrast. This review highlights the important research on temperature–dependent electrochromic properties in recent years. Also, the reported structures, mechanisms, characteristics, and methods for improving electrochromic properties are discussed in detail. In addition, the challenges and corresponding strategies in this field are presented in this paper. This paper will inspire more researchers to enrich the temperature–dependent properties of ECDs and their related fields with innovative means and methods to overcome the technical obstacles faced. [ABSTRACT FROM AUTHOR]

In the present work, the momentum fluxes of gravity wave (GW) around the mesopause are estimated, using the decadal continuous observations by meteor radar at Mohe (53.5°N, 122.3°E). Applying the Hocking's (2005) approach with the modified-composite-day (MCD) analysis, the GW momentum fluxes of short-periods (less than 2 h) are estimated month by month. As the first step, several experiments are designed to evaluate the accuracy and uncertainty in the estimation. The results show that Mohe meteor radar has the ability to give reasonable estimations on the GW momentum fluxes at a height of 82–94 km, in which errors are generally less than 5 m2/s2. The uncertainty induced by different angular information of the detected meteor in each month achieves ~2 m2/s2. It is inferred that the variability of the GW momentum fluxes over 2 m2/s2 can be distinguished in the observation. The interannual variation of the estimated GW momentum fluxes show a significant enhancement in 2012, and a depression in 2013, with a fluctuation over ±10 m2/s2 at 82 km. However, no obvious quasi-biennial oscillation (QBO) -like signal has been found in the Lomb–Scargle periodogram. [ABSTRACT FROM AUTHOR]

Space objects around the Earth are a potential pollution source for ground-based radio observations. 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), with the main purpose of ionospheric monitoring and investigations. In this study, we presented the effect of the greatly increased number of space objects on ionospheric observations through SYISR. Firstly, we showed the space object pollution on the range-time-intensity (RTI), autocorrelation function (ACF)/power spectra, and ionosphere parameter of SYISR measurements. An altitude of around 600 km is the region where space objects occur most frequently. Then, we eliminated the space object pollution using the traditional smallest of constant-false-alarm-rate (SO-CFAR) algorithm. However, pollution from smaller space objects remains, whose reflected echo is comparable to or lower than the background ionosphere, which results in unrealistic retrieved ionospheric electron density. Furthermore, we quantitatively assessed the space object effect based on the current space object orbit database and simulation. The pollution should linearly increase with the increase in the number of space objects in the future. Among the space objects, whose radar cross section (RCS) and orbit information are now published, there still exist ~9000 (~37% of the total number) space objects, whose effect is difficult to eliminate. This study is beneficial to the data process of SYISR and has implications for similar types of ionospheric observations by radar. [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]

To extend existing distance metrics in the $L^{p}$ space, we define a novel distance, named relative Euclidean distance (RED), and prove that it is positive definite, symmetric, and satisfies the triangle inequality. This distance has a value range of [0, 1]. We prove a uniqueness of it in the $L^{p}$ space. The technique for order preference by similarity to ideal solution (TOPSIS) is widely used for multiple-attribute decision problems. The commonly used relative closeness measure in the TOPSIS is not a mathematical distance and thus does not have all the nice properties of such a distance. To improve the TOPSIS, particularly its relative closeness measure, we propose two measures, named optimistic distance (OD) and pessimistic distance (PD), based on our RED, and use them to measure the relative closeness in the TOPSIS. Both measures are positive definite, symmetric, and satisfy the triangle inequality. The best choice in OD (or PD) is on the Pareto frontier. Three examples of performance ranking are given to illustrate the usefulness of the TOPSIS with our proposed measures. [ABSTRACT FROM AUTHOR]

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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]

This article discusses a case of Adie's tonic pupil in a 37-year-old Asian woman with primary Sjögren syndrome. The patient presented with symptoms of dry eyes, dry mouth, bilateral dilated pupils, and blurred vision. Further examination revealed irregular shaped pupils and a sluggish response to light. The presence of Adie's tonic pupil was confirmed through pharmacological testing. The article emphasizes the importance of recognizing this rare manifestation of Sjögren syndrome for early diagnosis and proper management. [Extracted from the article]

In conclusion, we present the first case of JAK inhibitor treatment for a patient with sarcoidosis who also had glaucoma, a relative contraindication to corticosteroids. This is the first case to provide significant evidence that JAK inhibitor is an effective treatment for both subcutaneous and pulmonary sarcoidosis, and it is also the first case in which tofacitinib was used in a patient who has a contraindication for corticosteroid therapy. [Extracted from the article]

Background: Radiofrequency ablation (RFA) is widely used in palliative therapy of malignant cancers. Several studies have shown its applicability and safety for locally advanced pancreatic cancer (LAPC). The objective of this study was to modify the current regimen to improve its therapeutic effect. Methods: Immune cell subtypes and related cytokines were quantified to uncover the immune pattern changes post-RFA treatment. Then, high-throughput proteome analysis was performed to identify differentially expressed proteins associated with RFA, which were further validated in in vitro and in vivo experiments. Finally, a combined therapy was tested in a murine model to observe its therapeutic effect. Results: In preclinical murine models of RFA treatment, no significant therapeutic benefit was observed following RFA treatment. However, the proportion of tumor-infiltrating CD8+ T cells was significantly increased, whereas that of regulatory T cells (Tregs) was decreased post-RFA treatment, which indicated a beneficial anti-tumor environment. To identify the mechanism, high-throughput mass spectrum was obtained that identified heat shock protein 70 (HSP70) as the top differentially expressed protein. HSP70 expression in residual cancer cells was significantly increased post-RFA treatment, which notably promoted pancreatic cancer growth. Elevated HSP70 promoted cell proliferation by activating AKT–mTOR signaling. Finally, RFA treatment combined with an mTOR inhibitor exerted a synergetic repressive effect on tumor growth in the preclinical murine cancer model. Conclusions: RFA treatment in combination with mTOR signaling blockade can not only promote tumor immune response, but also restrain residual cancer cell proliferation. Such a combination may be a promising and effective therapeutic strategy for LAPC patients. [ABSTRACT FROM AUTHOR]

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]

On examination, we saw puffy fingers, periungual erythema, dilated capillaries and hemorrhages of the proximal nail folds in all fingers except her thumbs. To observe nail fold capillaries more clearly, placing a dermatoscope on the proximal nail fold can show capillaries appearing as small red dots or loops. [2] Nail fold capillary abnormalities, especially hemorrhages and giant capillaries, are sometimes visible to the unaided eye. [Extracted from the article]

Given multiple statistical estimators, how to rank their performance is a worthwhile problem. We propose an approach to estimation performance ranking based on pairwise comparison. Because ranking is about two or more estimators and is relative, pairwise comparison (e.g., Pitman’s measure of closeness) suits the needs. However, pairwise comparison cannot guarantee transitivity, which is needed for ranking. To get around this problem, we propose a ranking vector (RV) approach based on pairwise comparison. Here, an RV is obtained by using pairwise comparison results without using pairwise ranks directly. An RV provides ordinal information determining the rank and also supplementary cardinal information exhibiting how much one estimator is better than another. Ordinal information is more important and thus is guaranteed by using an order-preserving mapping in obtaining an RV. Our RV approach based on pairwise comparison is also applied to multiple-attribute decision problems. The approach is easily applicable and it does not need data normalization. [ABSTRACT FROM AUTHOR]

Background: The prognosis of pancreatic carcinoma (PC) remains poor and the American Joint Committee on Cancer (AJCC) 8th staging system for survival prediction in PC patients after curative resection is still limited. Thus, the aim of this study is to refine a valuable prognostic model and novel staging system for PC with curative resection. Methods: The data of 3,458 patients used in this study were retrieved from the Surveillance, Epidemiology, and End Results database registry of National Cancer Institute. The prognostic value of lymph node ratio (LNR) was analyzed in the primary cohort and prognostic nomogram based on the LNR was established to create a novel staging system. Then, analyses were conducted to evaluate the application of the formulated nomogram staging system and the AJCC 8th staging system. The predictive performance of model was further validated in the internal validation cohort. Results: Significant positive correlations were found between LNR and all factors except for surgical procedures. The results of univariate and multivariate analyses showed that LNR was identified as an independent prognostic indicator for overall survival (OS) in both primary and validation cohorts (all P < 0.001). A prognostic nomogram based on the LNR was formulated to obtain superior discriminatory abilities. Compared with the AJCC 8th staging system, the formulated nomogram staging system showed higher hazard ratios of stage II, III, and IV disease (reference to stage I disease) that were 1.637, 2.300, and 3.521, respectively, by univariate analyses in the primary cohort and the distinction between stage I, II, and III disease at the beginning or end of the survival curves was more apparent. All these results were further verified in the validation cohort. Conclusion: LNR can be considered as a useful independent prognostic indicator for PC patients after curative resection regardless of the surgical procedures. Compared with the AJCC 8th staging system, the formulated nomogram showed superior predictive accuracy for OS and its novel staging system revealed better risk stratification. [ABSTRACT FROM AUTHOR]