NPS: A Framework for Accurate Program Sampling Using Graph Neural Network

With the end of Moore's Law, there is a growing demand for rapid architectural innovations in modern processors, such as RISC-V custom extensions, to continue performance scaling. Program sampling is a crucial step in microprocessor design, as it selects representative simulation points for workload simulation. While SimPoint has been the de-facto approach for decades, its limited expressiveness with Basic Block Vector (BBV) requires time-consuming human tuning, often taking months, which impedes fast innovation and agile hardware development. This paper introduces Neural Program Sampling (NPS), a novel framework that learns execution embeddings using dynamic snapshots of a Graph Neural Network. NPS deploys AssemblyNet for embedding generation, leveraging an application's code structures and runtime states. AssemblyNet serves as NPS's graph model and neural architecture, capturing a program's behavior in aspects such as data computation, code path, and data flow. AssemblyNet is trained with a data prefetch task that predicts consecutive memory addresses. In the experiments, NPS outperforms SimPoint by up to 63%, reducing the average error by 38%. Additionally, NPS demonstrates strong robustness with increased accuracy, reducing the expensive accuracy tuning overhead. Furthermore, NPS shows higher accuracy and generality than the state-of-the-art GNN approach in code behavior learning, enabling the generation of high-quality execution embeddings

Anti-BP180 Autoantibodies Are Present in Stroke and Recognize Human Cutaneous BP180 and BP180-NC16A

Objective: Current evidence has revealed a significant association between bullous pemphigoid (BP) and neurological diseases (ND), including stroke, but the incidence of BP autoantibodies in patients with stroke has not previously been investigated. Our study aimed to assess BP antigen-specific antibodies in stroke patients.Design: One hundred patients with stroke and 100 matched healthy controls were randomly selected for measurement of anti-BP180/BP230 IgG autoantibodies by enzyme-linked immunosorbent assay (ELISA), salt-split indirect immunofluorescence (IIF), and immunoblotting against human cutaneous BP180 and BP180-NC16A.Results: Anti-BP180 autoantibodies were found in 14 (14.0%) patients with stroke and 5 (5.0%) of controls by ELISA (p < 0.05). Sera from 13 (13.0%) patients with stroke and 3 (3.0%) controls reacted with 180-kDa proteins from human epidermal extract (p < 0.05). 11 (11.0%) of stroke and 2 (2.0%) of control sera recognized the human recombinant full length BP180 and NC16A (p < 0.05). The anti-BP180-positive patients were significantly younger than the negative patients at the time of stroke (p < 0.001).Conclusion: Development of anti-BP180 autoantibodies occurs at a higher frequency after stroke, suggesting BP180 as a relatively common autoantigen after stroke and providing novel insights into BP pathogenesis in aging

Advances in the diagnosis and treatment of cutaneous T-cell lymphoma

Mycosis fungoides (MF) and Sezary syndrome (SS) are important representatives of the heterogeneous group of cutaneous T-cell lymphoma. The diagnosis of MF/SS is based on the clinical, histopathologic and immunohistochemical findings, flow cytometric analysis of peripheral blood and T-cell receptor gene rearrangement, as well as other genetic analysis. The treatments for MF/SS are always stage-oriented and are classified into topical (skin-directed) and systemic therapies. Chinese and international experts in this field have updated recommendations and guidelines for the diagnosis and treatment of MF/SS. There are tremendous evolvements in the diagnosis of MF/SS, including molecular diagnostic methods, molecular biomarkers, dermoscopic imaging and artificial intelligence. Novel disease-specific targeted therapy, biologic therapy and immunomodulatory drugs have emerged. This review summarizes advances in the diagnosis and treatments of MF/SS, which may provide a reference for clinical practice and future research

Reduction of Methyltransferase-like 3-Mediated RNA N6-Methyladenosine Exacerbates the Development of Psoriasis Vulgaris in Imiquimod-Induced Psoriasis-like Mouse Model

N6-methyladenosine (m6A) methylation is the most pervasive and intensively studied mRNA modification, which regulates gene expression in different physiological processes, such as cell proliferation, differentiation, and inflammation. Studies of aberrant m6A in human diseases such as cancer, obesity, infertility, neuronal disorders, immune diseases, and inflammation are rapidly evolving. However, the regulatory mechanism and physiological significance of m6A methylation in psoriasis vulgaris are still poorly understood. In this study, we found that m6A methylation and Methyltransferase-like 3 (METTL3) were both downregulated in psoriatic skin lesions and were negatively correlated with Psoriasis Area and Severity Index (PASI) scores. Inhibiting m6A methylation by knocking down Mettl3 promoted the development of psoriasis and increased its severity in imiquimod-induced psoriasis-like model mice. Our results indicate a critical role of METTL3- mediated m6A methylation in the pathogenesis of psoriasis vulgaris

Research progress of metabolomics in psoriasis

Abstract. Psoriasis is a chronic inflammatory skin disease with significant physical and psychological burdens. The interplay between the innate and adaptive immune systems is thought to contribute to the pathogenesis; however, the details of the pathogenesis remain unclear. In addition, reliable biomarkers for diagnosis, assessment of disease activity, and monitoring of therapeutic response are limited. Metabolomics is an emerging science that can be used to identify and analyze low molecular weight molecules in biological systems. During the past decade, metabolomics has been widely used in psoriasis research, and substantial progress has been made. This review summarizes and discusses studies that applied metabolomics to psoriatic disease. These studies have identified dysregulation of amino acids, carnitines, fatty acids, lipids, and carbohydrates in psoriasis. The results from these studies have advanced our understanding of: (1) the molecular mechanisms of psoriasis pathogenesis; (2) diagnosis of psoriasis and assessment of disease activity; (3) the mechanism of treatment and how to monitor treatment response; and (4) the link between psoriasis and comorbid diseases. We discuss common research strategies and progress in the application of metabolomics to psoriasis, as well as emerging trends and future directions

Systemic monotherapy with acitretin for erythrodermic psoriasis: results of a retrospective study of 81 patients

Background: Erythrodermic psoriasis (EP) remains challenging to manage because it is rare and has complex complications. Although acitretin is recommended as an appropriate choice for EP, there is a lack of large-scale evidence. Objectives: This study aims to assess the efficacy and safety of acitretin as systemic monotherapy in EP patients. Design: We retrospectively analyzed data from patients with EP who received at least 3 months of acitretin as systemic monotherapy during hospitalization and out-patient follow-up from January 2005 to May 2021 at the Peking Union Medical College Hospital, China. Methods: The efficacy was clinically evaluated after 1, 2, 4, and 12 weeks of treatment, which was classified as a good response (>75% of lesions cleared), partial response (50%–75% cleared), moderate response (25–50% cleared), or no response (<25% cleared). Safety was assessed on the basis of physical examination results and significant changes in laboratory examination results after 12 weeks of treatment. Results: Overall, 81 patients (79.0% men; mean age, 47.9 years) were included. The acitretin dose ranged from 20 to 60 mg/day (0.3 to 0.8 mg/kg/day). The rates of good, partial, and moderate responses were 0.0%, 2.5%, and 42.0% at 1 week; 3.7%, 34.6%, and 61.7% at 2 weeks; 29.6%, 58.0%, and 12.4% at 4 weeks; and 85.2%, 13.6%, and 1.2% at 12 weeks after treatment initiation, respectively. EP patients transformed from psoriasis vulgaris showed a higher good/partial response rate compared with that of EP patients that developed from pustular or articular psoriasis (44.6% vs. 14.3%, p  = 0.035). Patients with concurrent infection showed a lower rate of good/partial response compared with that of those without concurrent infection (16.7% vs. 44.4%, p  = 0.049). Adverse effects were seen in 45 (55.6%) patients in 12 weeks, and dyslipidemia ( n  = 31; 38.3%), xerosis ( n  = 24; 29.6%), and elevated liver enzymes ( n  = 6; 7.4%) were most commonly reported. Twenty-three patients were followed up for over 3 years, and six (26.1%) patients had EP recurrence. Conclusions: Acitretin as a systemic monotherapy showed satisfactory effectiveness for EP, especially in patients developed from psoriasis vulgaris and without infection