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摘要： Objective: In order to examine the usefulness of anti-β2GPI/HLA-DR antibody (neoself antibody) test in infertility and recurrent miscarriage, we analyzed the results of the neoself antibody test performed at our clinic and the subsequent treatment...

关键词： Clinical phenotypes   Juvenile dermatomyositis   Myositis-specific autoantibodies   Targeted therapies   Type 1 IFNs  

摘要： Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is associated with significant morbidity despite therapeutic advances. Distinct clinical phenotypes have emerged, which can correlate with myositis-specific antibodies. Because translational data solidify the role of type I IFNs in JDM disease pathogenesis, integration of clinical and molecular phenotyping may impact the choice of targeted therapy. This paper reviews clinical and molecular phenotyping in JDM and translational insights into immune pathogenesis that have created emerging options for targeted therapy. Targeted therapies, Type 1 IFNs

关键词： adolescents   mental health   mental illness   validation   well-being  

摘要： AimThe Mental Health Continuum-Short Form (MHC-SF) is an assessment tool used worldwide to assess emotional, social, and psychological well-being. This study examined the structure, reliability, and validity of the Japanese version of the MHC-SF among adolescents. MethodsIn total, 1588 adolescents aged 15-18 years completed the assessment (54.8% female;age mean +/- standard deviation = 16.3 +/- 0.94 years). The factor structure of the MHC-SF was evaluated using confirmatory factor analyses. The internal consistency, concurrent validity, and measurement invariance across sex and age were examined. ResultsA three-factor model of the MHC-SF yielded the best fit compared with the one- and two-factor models. Internal consistency was confirmed by a Cronbach's alpha (>0.8). Measurement invariance was observed across sex and age. Convergent and divergent validity were demonstrated by assessing the relationships with other measurements. ConclusionThis study established a three-factor model of the MHC-SF in Japanese adolescents. We confirmed the reliability and validity of the Japanese version of the MHC-SF for assessing emotional, social, and psychological well-being in adolescents.

关键词： Cytomegalovirus   Epstein-Barr virus   Thymoglobulin   Adult T -cell leukemia/lymphoma   Letermovir  

摘要： We retrospectively analyzed early post-transplant infections in high-risk hematological malignancy patients who underwent HLA-mismatched HSCT using low-dose thymoglobulin (ATG), and the results were compared with patients underwent HSCT without ATG. There were no significant between-group differences in the incidence of viral or fungus infections. However, earlier CMV reactivation and higher incidence of EBV viremia were observed in ATG patients. Background: In vivo T-cell depletion with antithymocyte globulin (ATG), especially at high-doses has been shown to be associated with increased incidence of infections after allogeneic hematopoietic stem cell transplantation (HSCT). However, it remains unclear whether ATG, even at low-doses increases the risk of posttransplant infections in the high-risk HSCT setting. Patients and Methods: We conducted a single-center retrospective study of viral and fungal infections early after transplantation, using the data from 82 patients with hematological malignancies. Among them, 42 underwent HLA-mismatched HSCT using low-dose (2.5 mg/kg n = 41, 2.0 mg/kg n = 1) thymoglobulin (ATG patients), and 40 control patients received HSCT without ATG (non-ATG patients) during the same period. Cord blood transplantation patients were excluded. All ATG patients had hematological malignancies not in remission at the time of transplantation, and were considered to be at high-risk for posttransplant infections. Results: There were no appreciable between-group differences in the incidence of clinically significant cytomegalovirus infection (csCMVi), late-onset CMV reactivation after discontinuation of letermovir, invasive fungal diseases or Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. Peak values of CMV antigenemia were almost equal in ATG and non-ATG patients. The prevention of csCMVi with letermovir was constant in the 2 groups. However, ATG patients showed earlier reactivation of CMV and higher incidence of EB

关键词： TOP1   Microglial activation   YY1   Sleep deprivation   Neopterin   Hippocampus  

摘要： Introduction: Sleep deprivation (SD) is a common disorder in modern society. Hippocampus is an important region of the brain for learning, memory, and emotions. Dysfunction of hippocampus can lead to severe learning and memory disorder, significantly affecting quality of life. SD is accompanied by hippocampal microglia activation and a surge in inflammatory factors, but the precise mechanism remains unclear. Moreover, the ongoing unknown persists regarding how activated microglia in SD lead to neuronal damage. Topoisomerase 1 (TOP1) plays an essential role in the inflammatory process, including the tumor system and viral infection. In this study, we observed a significant elevation in TOP1 levels in the hippocampus of mice subjected to SD. Therefore, we hypothesize that TOP1 may be implicated in SD-induced microglia activation and neuronal damage. Objectives: To investigate the role of TOP1 in SD-induced microglial activation, neuronal damage, and neurobehavioral impairments, and the molecular basis of SD-induced elevated TOP1 levels. Methods: TOP1-specific knockout mice in microglia were used to study the effects of TOP1 on microglial activation and neuronal damage. Transcription factor prediction, RNA interference, ChIP-qPCR, ChIP-seq database analysis, and luciferase reporter assays were performed to explore the molecular mechanisms of YY1 transcriptional activation. Untargeted metabolic profiling was employed to investigate the material basis of YY1 transcriptional activation. Results: Knockdown of TOP1 in hippocampal microglia ameliorates SD-induced microglial activation, inflammatory response, and neuronal damage. Mechanistically, TOP1 mediates the release of IL-6 from microglia, which consequently leads to neuronal dysfunction. Moreover, elevated TOP1 due to SD were associated with neopterin, which was attributed to its promotion of elevated levels of H3K27ac in the TOP1 promoter region by disrupting the binding of YY1 and HDAC1. Conclusion: The present study

关键词： Outcome measures   Safety   biological DMARD   Observational studies/ registry  

关键词： Advanced epithelial ovarian cancer   IL-12   Gene therapy   Immunotherapy  

摘要： Objective. OVATION-2, a randomized, controlled, open label phase 1/2 study, evaluated the safety and efficacy of IMNN-001, an IL-12 immune gene therapy, with neo/adjuvant chemotherapy (N/ACT) compared to N/ACT in newly-diagnosed advanced epithelial ovarian cancer (EOC). Methods. IMNN-001 is an immunotherapeutic nanoparticle comprising a DNA plasmid encoding the IL-12 gene encased in a lipopolymer. High-grade EOC patients were randomized 1:1 to carboplatin/paclitaxel IV every 21 days for 3 cycles, before and after interval debulking surgery (IDS) or to intraperitoneal (IP) IMNN-001, given weekly concurrently with chemotherapy for 8 weeks before and 9 weeks after IDS. Results. 54 and 58 patients with predominantly Stage IIIC/IV EOC were evaluated in the control and experimental arm, respectively. Primary endpoints were safety and PFS. Overall, the experimental arm was well tolerated with gastrointestinal and cytopenias as the most common TEAEs with no CRS or elevated risk of immune events. PFS was 14.9 months (mo) for the experimental arm vs 11.9 mo;HR 0.79 (95% CI: 0.51-1.23). Secondary endpoints included OS (46.0 mo for experimental arm vs 33.0 mo;HR 0.69 (CI: 0.40-1.19)) and surgical response R0 rate (64.6% experimental arm vs 52.1 %). For patients who received PARPi maintenance, PFS was 33.8 mo vs 22.1 mo;HR 0.80 (CI: 0.31-2.12) and OS was NE vs 37.1 mo with a HR of 0.38 (CI: 0.13-1.06) both favoring the experimental arm. Conclusion. The addition of IMNN-001 to N/ACT shows a promising numerical 13-mo benefit on survival with an acceptable safety profile in patients with newly-diagnosed advanced EOC. (c) 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// ***/licenses/by/4.0/).

关键词： biological DMARD   Targeted synthetic drugs   Comorbidities   Biomarkers  

关键词： major histocompatibility complex   HLA   transplantation   physical crossmatch   virtual crossmatch   histocompatibility testing  

摘要： Pretransplantation human leukocyte antigen antibody testing is necessary to assess compatibility between donor and recipient pairs. Over the past decade, the virtual crossmatch (VXM) has replaced the physical crossmatch (PXM) as the main assessment of pretransplant histocompatibility. At our center, most transplants have proceeded based solely on the VXM, followed by a retrospective PXM. In this study, we sought to determine whether VXMs alone are sufficient and if routine retrospective PXMs can be discontinued. A review of PXMs for single solid organ transplant cases between May 19, 2020, and December 9, 2022, was performed to examine the concordance between the PXM and VXM (including predictions of the PXM made in the VXM report). The relationship between PXM results and donor-specific antibody (DSA) mean fluorescence intensity values was also examined. The overall PXM prediction/PXM result concordance rate was 99.7% based on PXMs attributed to human leukocyte antigen antibody. Furthermore, DSA mean fluorescence intensity values can guide clinical decisions on whether to perform a PXM. The data confirm that, in the era of the VXM, routine PXMs performed for all transplants are not warranted. However, a PXM may still be informative in select cases where low-tointermediate strength DSAs are present or when the virtual assessment is ambiguous.

关键词： TNF   PTPRT   Goat   InDel   Brucella  

摘要： Brucella, an intracellular facultative coccidia, causes brucellosis, which poses a significant threat to livestock farming and public health, and screening for candidate genes associated with resistance to brucellosis is considered an effective strategy for controlling the transmission and infection of this disease. In this context, we detected InDel genetic variants of the tumor necrosis factor (TNF) and protein tyrosine phosphatase receptor T (PTPRT) genes in the Shaanbei White Cashmere (SWBC) goat and analyzed the correlation between their polymorphisms and the risk of brucellosis infection in goats. The results indicated that the TNF rs669191919 and PTPRT rs639317914 loci were polymorphic in the examined goat populations. Both loci exhibited a 13 bp InDel deletion and resulted in three genotypes: insertion/insertion (II), insertion/deletion (ID), and deletion/deletion (DD), with II genotypes and I alleles occurring at higher frequencies. The polymorphism information content (PIC) values suggested that both InDel variant loci were moderately polymorphic (0.25 < PIC <0.50). Furthermore, association analysis revealed that none of the four established genetic models codominant, dominant, recessive, and allele showed an association between the polymorphisms at the rs669191919 and rs639317914 loci and the risk of brucellosis in goats (P > 0.05). Bioinformatics analyses indicated that the rs669191919 and rs639317914 loci specifically bind to the transcription factors upstream transcription factor 1 (USF1) and nescient helix-loop-helix 1 (NHLH1), respectively. In summary, our findings suggest that polymorphisms at the TNF rs669191919 and PTPRT rs639317914 loci do not influence resistance to brucellosis in goats. However, investigations into the specific binding of these polymorphic loci to transcription factors may represent a novel avenue for exploring the mechanisms underlying resistance to brucellosis in livestock.