Stem-like and effector peripheral helper T cells comprise distinct subsets in rheumatoid arthritis.

Peripheral helper T (T) cells can play pathogenic roles in human autoimmune diseases. T cells are proposed to be the major B cell helpers in inflamed joints in rheumatoid arthritis (RA), but whether and how T cells are engaged in tissue inflammation remains unclear. We demonstrate that T cells comprise two subsets in RA: stem-like T (S-T) and effector T (E-T) cells.

Human CD4 T cells regulate peripheral immune responses in rheumatoid arthritis via insulin-like growth factor-like family member 2.

Human CD4 T cells play a central role in the pathogenesis of autoimmune diseases, but their immunoregulatory mechanisms driving pathogenesis remain to be elucidated. We show that human T peripheral helper cells (T cells) regulate peripheral immune responses via insulin-like growth factor-like family member 2 (IGFL2), an inflammatory factor found exclusively in primates. Single-cell RNA sequencing of seropositive rheumatoid arthritis (RA) synovium showed that is specifically expressed by CD4 T cells, predominantly T cells.

Comprehensive Analysis of N6-Methyladenosine (m6A) RNA Methylation Regulators in Soft Tissue Leiomyosarcoma.

N6-methyladenosine (m6A), a widespread RNA modification, plays a vital role in various biological processes, including carcinogenesis, tumor progression, and immune regulation. We conducted this study to investigate the relationship between m6A regulators, such as METTL3, METTL14, WTAP, FTO, ALKBH5, and YTHDF1-3, and their association with c-Myc and programmed death ligand 1 (PD-L1) expression in leiomyosarcoma (LMS). The expression of these epitranscriptome regulator genes was evaluated using the next-generation sequencing data of 53 patients with LMS obtained from an online public database.

Expression of Signal Regulatory Protein Alpha in Tumor Cells is the Key Factor in Intrahepatic Cholangiocarcinoma.

Background: Signal-regulatory protein alpha (SIRPα) has recently garnered attention for its role in the immune system, commonly referred to as the "don't eat me" signal. However, the relationship between SIRPα expression in tumor cells and prognosis in patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) has been scarcely reported.

Patients And Methods: A total of 117 patients who underwent hepatectomy for ICC were enrolled in this study.

Roles of JAK-STAT signaling and granulocyte-macrophage colony-stimulating factor in the development of osteitis and bone microstructure changes in rheumatoid arthritis.

Background: Osteitis on magnetic resonance imaging (MRI) and bone microstructure changes (BMC) on high-resolution peripheral quantitative computed tomography (CT) are the earliest signs of arthritis, preceding the development of bone erosion on X-ray in rheumatoid arthritis (RA). Recently, a Janus kinase (JAK) inhibitor, baricitinib, reportedly suppresses these early changes. This study aimed to elucidate the underlying molecular mechanism of osteitis and BMC using an animal model of RA and human samples.

Multiscale Fusion Models With Genomic, Topological, and Pathomic Features to Predict Response to Radiation Therapy for Non-Small Cell Lung Cancer Patients.

Artificial intelligence models with biomarkers to predict treatment responses to radiation would be necessary to maximize the treatment outcomes of individual patients, especially with histopathology images routinely obtained before treatment. We hypothesized that multiscale features, such as genomic (GM), pathomic (PM), and topological (TP) features, could be associated with the radiation response. We investigated fusion models with multiscale features in histopathology images to predict response to radiation therapy for patients (responders) with non-small cell lung cancer.

[A Case of Rectal Metastasis from Prostate Cancer].

A 78-year-old male was under follow-up after gallbladder cancer surgery when CT imaging revealed thickening of the rectal wall, along with enlarged mesenteric and left-sided lymph nodes. Colonoscopy identified a semi-circumferential, tumor-like lesion in the lower rectum, and biopsy results confirmed a diagnosis of poorly differentiated adenocarcinoma. Pelvic MRI further revealed a separate tumor in the prostate, leading to a diagnosis of concurrent rectal and prostate cancer.

Critical roles of chronic BCR signaling in the differentiation of anergic B cells into age-associated B cells in aging and autoimmunity.

Age-associated B cells (ABCs) with autoreactive properties accumulate with age and expand prematurely in autoimmune diseases. However, the mechanisms behind ABC generation and maintenance remain poorly understood. We show that continuous B cell receptor (BCR) signaling is essential for ABC development from anergic B cells in aged and autoimmune mice.

Differences in Tumor-Infiltrating Lymphocyte Counts in the Peritumoral Area in Patients Undergoing Hepatic Resection After Lenvatinib and Atezolizumab Plus Bevacizumab Therapy for Hepatocellular Carcinoma.

Aim: With advances in systemic therapy, the number of patients with hepatocellular carcinoma (HCC) who can undergo hepatic resection has increased in recent years, but there are no reports evaluating the immune status in the peritumoral area.

Methods: We enrolled 14 patients who underwent hepatic resection after lenvatinib (LEN, n = 7) or atezolizumab plus bevacizumab (ATZ/BEV, n = 5) therapy. Tumor-infiltrating lymphocytes (TILs), including CD3+ and CD8+ TILs, in the peritumoral area were evaluated by hematoxylin and eosin staining and immunohistochemistry.

Impact of Tertiary Lymphoid Structure on Prognosis and Tumor Microenvironment in Undifferentiated Pleomorphic Sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) has a favorable objective response rate to anti-PD-1 drugs compared with other sarcomas. Tertiary lymphoid structure (TLS) is a favorable prognostic factor and a biomarker for immune checkpoint inhibitors (ICIs). Nevertheless, there are limited data on the tumor microenvironment (TME) to support a good response to ICIs in sarcoma.

The Association of Anti-dsDNA Antibodies with Patient-reported Outcomes of Patients with Systemic Lupus Erythematosus in a Two-consecutive Year Prospective Study.

Objectives: To analyse the association of anti-dsDNA Ab with patient-reported outcomes (PROs) in patients with SLE under maintenance treatment, as it has not been clearly understood whether PROs are able to be reflected by anti-dsDNA, which are associated with SLE activities (SLE Disease Activity Index 2000, SLEDAI-2K).

Methods: The SLE symptom checklist (SSC), LupusPRO, Medical Outcomes Study Short Form-36 (SF-36), and patient and physician visual analogue scale (Pt/Ph-VAS) at a time point were evaluated for correlation with anti-dsDNA using the Kyoto Lupus Cohort Registry (n = 310) from 2019 to 2020. Further, associations between changes in anti-dsDNA with those in Pt/Ph-VAS and SSC at two time points of short-term (3 months) or long-term (2 years) time points.

Memory B cells and their transcriptomic profiles associated with belimumab resistance in systemic lupus erythematosus in the maintenance phase.

The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in the maintenance phase are unknown. Here, we collected blood samples from patients with SLE (n=44) treated with belimumab before and three and six months after treatment. RNA-Seq of whole blood was performed, and gene expression was quantified.

Adjunctive diagnostic tool for histopathological classification of congenital mesoblastic nephroma based in molecular genetic findings.

Purpose: Congenital mesoblastic nephromas (CMN) are histologically classified into classical, cellular, and mixed subtypes. Most cellular CMNs harbor ETV6-NTRK3 gene fusions, and classic and mixed CMNs harbor EGFR internal tandem duplications (EGFR-ITDs). Classic CMNs are considered benign, whereas recurrent or metastatic diseases occur in the cellular subtypes.

Deep learning model to diagnose cardiac amyloidosis from haematoxylin/eosin-stained myocardial tissue.

Aims: Amyloid deposition in myocardial tissue is a definitive feature for diagnosing cardiac amyloidosis, though less invasive imaging modalities such as bone tracer cardiac scintigraphy and cardiac magnetic resonance imaging have been established as first steps for its diagnosis. This study aimed to develop a deep learning model to support the diagnosis of cardiac amyloidosis from haematoxylin/eosin (HE)-stained myocardial tissue.

Methods And Results: This single-centre retrospective observational study enrolled 166 patients who underwent myocardial biopsies between 2008 and 2022, including 76 patients diagnosed with cardiac amyloidosis and 90 with other diagnoses.

Loss of SMARCA4 induces sarcomatogenesis through epithelial-mesenchymal transition in ovarian carcinosarcoma.

Ovarian carcinosarcoma (OCS) is a rare and aggressive tumor, and the development of its sarcomatous component is believed to be due to epithelial-mesenchymal transition (EMT). The SWIch/sucrose nonfermentable chromatin remodeling factor (CRF) is closely related to EMT; however, the relationship between CRF and EMT in OCS remains unclear. In this study, we analyzed the protein expression of CRFs, including ARID1A and SMARCA4, and their downstream mRNA expression in 28 OCS cases, two fallopian tube CS cases, and one peritoneal CS case.

Clinical and pathological characteristics of immune checkpoint inhibitor-related fulminant myocarditis.

The advent of immune checkpoint inhibitors (ICIs) has significantly improved cancer treatment. With the increasing use of ICIs, ICI-related myocarditis has been recognized. However, an evidence-based therapeutic strategy has not been established because of the limited knowledge on ICI-related myocarditis.

Factors affecting discrepancies in disease activity evaluation between patients and physicians in systemic lupus erythematosus-The importance of symptoms such as fatigue.

Objectives: There are often discrepancies in the evaluation of disease activity between patients and physicians in systemic lupus erythematosus (SLE). In this study, we examined the factors that affect those evaluations.

Methods: Physician visual analogue scale (Ph-VAS), patient VAS (Pt-VAS), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k), glucocorticoid (GC) usage and dose, age, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and three patient-reported outcomes (SLE symptom checklist [SSC], short-form 36 questionnaire [SF-36], and LupusPRO) were obtained from a study performed in 2019 using 225 SLE outpatients of the Kyoto Lupus Cohort at Kyoto University Hospital.

The Association of Transferrin Receptor with Prognosis and Biologic Role in Intrahepatic Cholangiocarcinoma.

Background: Ferroptosis is a cell death caused by iron-dependent accumulation of lipid peroxidation. Transferrin receptor (TFR) is a ferroptosis-related protein responsible for iron transport. The detailed biologic role of TFR in intrahepatic cholangiocarcinoma (ICC) is not fully elucidated.

Papillary renal neoplasm with reverse polarity has low frequency of alterations in chromosomes 7, 17, and Y.

In papillary renal neoplasm with reverse polarity (PRNRP), the status of chromosomal copy number alterations, especially chromosomes 7/17 gain and chromosome Y loss, has remained controversial. In the literatures, there is a discrepancy among the results of chromosomal alteration in PRNRP depending on the analytical methods. Here, we comprehensively analyzed the status of chromosomal abnormalities in PRNRP.