Glucocorticoid tapering pace in microscopic polyangiitis and granulomatosis with polyangiitis in Japanese real-world practice: A propensity score-matched retrospective cohort study from the J-CANVAS registry.

Objective: To assess the prevalence and outcomes among regimens of glucocorticoid tapering for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in real-world practice.

Methods: We retrospectively examined the Japan Collaborative Registry of ANCA-associated Vasculitis (J-CANVAS) registry, and evaluated the prevalence of glucocorticoid tapering regimens in the PEXIVAS trial. In patients with newly diagnosed MPA and GPA, we compared outcomes among standard and reduced pace regimens.

Ancient genomics support deep divergence between Eastern and Western Mediterranean Indo-European languages.

The Indo-European languages are among the most widely spoken in the world, yet their early diversification remains contentious. It is widely accepted that the spread of this language family across Europe from the 5th millennium BP correlates with the expansion and diversification of steppe-related genetic ancestry from the onset of the Bronze Age. However, multiple steppe-derived populations co-existed in Europe during this period, and it remains unclear how these populations diverged and which provided the demographic channels for the ancestral forms of the Italic, Celtic, Greek, and Armenian languages.

Olig2+/NG2+/BLBP+ astrocyte progenitors: a novel component of the neurovascular unit in the developing mouse hippocampus.

Astrocytes are key components of the neurovascular unit. While we have recently identified Olig2+ astrocyte progenitors (ASPs) in the developing mouse dentate gyrus (DG), their molecular signature remains incompletely characterized. Here we demonstrate that Olig2+ ASPs predominantly express brain lipid-binding protein (BLBP), while only a small population of them expresses -GFP.

Overlap of Sjögren's Syndrome and Immune-Mediated Necrotizing Myopathy With Interstitial Lung Disease: A Case Report.

Immune-mediated necrotizing myopathy (IMNM), an inflammatory muscle disease, typically presents as severe muscle weakness due to immunologic mechanisms. Some cases also show cutaneous manifestations, interstitial lung disease, and sicca symptoms. In this report, we present a unique case of an elderly man with a history of mild and stable Sjögren's syndrome (SS) for over 10 years, who later developed interstitial lung disease and myositis, leading to a diagnosis of IMNM confirmed by the presence of anti-signal recognition particle antibodies.

Exploring RNA-guided DNA scissors in eukaryotes: Are Fanzors counterparts of CRISPR-Cas12s?

Fanzors are recently characterized RNA-guided DNA endonucleases found in eukaryotic organisms. In this issue of Cell, Xu, Saito et al. reveal the structural diversity of Fanzors and identify key features shared with TnpB and Cas12 proteins, providing a comprehensive perspective on their molecular function and evolution.

Differentiation stage-specific expression of transcriptional regulators for epithelial mesenchymal transition in dentate granule progenitors.

During the development of the mouse dentate gyrus (DG), granule neuronal progenitors (GNPs) arise from glial fibrillary acidic protein (GFAP)-expressing neural stem cells in the dentate notch. However, the transcriptional regulators that control their stepwise differentiation remain poorly defined. Since neurogenesis involves epithelial-to-mesenchymal transition (EMT)-like processes, we investigated the spatio-temporal expression profiles of the EMT transcription factors Zeb1, Scratch2 (Scrt2) and Nkx6-2 in relation to known GNP markers.

Effectiveness and safety of rituximab in severely relapsed antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective analysis of a Japanese multicentre cohort from the J-CANVAS.

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24.

Structural basis for pegRNA-guided reverse transcription by a prime editor.

The prime editor system composed of Streptococcus pyogenes Cas9 nickase (nSpCas9) and engineered Moloney murine leukaemia virus reverse transcriptase (M-MLV RT) collaborates with a prime editing guide RNA (pegRNA) to facilitate a wide variety of precise genome edits in living cells. However, owing to a lack of structural information, the molecular mechanism of pegRNA-guided reverse transcription by the prime editor remains poorly understood. Here we present cryo-electron microscopy structures of the SpCas9-M-MLV RTΔRNaseH-pegRNA-target DNA complex in multiple states.

Deciphering the association between biopsy-confirmed systemic small vessel vasculitis and Epstein-Barr virus-positive polymorphic B-cell lymphoproliferation.

The Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders (LPD). Additionally, EBV infection has correlated with diverse autoimmune diseases. However, the association between EBV and systemic small vessel vasculitis (SVV) remains controversial.

PurA is the main target of aurodox, a type III secretion system inhibitor.

Anti-microbial resistance (AMR) is one of the greatest threats to global health. The continual battle between the emergence of AMR and the development of drugs will be extremely difficult to stop as long as traditional anti-biotic approaches are taken. In order to overcome this impasse, we here focused on the type III secretion system (T3SS), which is highly conserved in many Gram-negative pathogenic bacteria.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

Objectives: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).

Methods: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.

Exploring the Role of Platelets in Virus-Induced Inflammatory Demyelinating Disease and Myocarditis.

Theiler's murine encephalomyelitis virus (TMEV) infection has been used as a mouse model for two virus-induced organ-specific immune-mediated diseases. TMEV-induced demyelinating disease (TMEV-IDD) in the central nervous system (CNS) is a chronic inflammatory disease with viral persistence and an animal model of multiple sclerosis (MS) in humans. TMEV infection can also cause acute myocarditis with viral replication and immune cell infiltration in the heart, leading to cardiac fibrosis.

Imaging features of mucinous carcinoma arising from mature teratoma showing cytokeratin 7+ and cytokeratin 20+ expression profile: A case report.

Ovarian mature teratomas are benign, but malignant transformation can occur infrequently, especially in women of advanced age. The tissue that undergoes malignant change is mostly squamous cell carcinoma, although adenocarcinoma has been reported in a small number of cases. The immunostaining results of adenocarcinoma usually show a cytokeratin (CK)7-/CK20+ expression profile, corresponding to lower gastrointestinal tract origin.

Embodied bidirectional simulation of a spiking cortico-basal ganglia-cerebellar-thalamic brain model and a mouse musculoskeletal body model distributed across computers including the supercomputer Fugaku.

Embodied simulation with a digital brain model and a realistic musculoskeletal body model provides a means to understand animal behavior and behavioral change. Such simulation can be too large and complex to conduct on a single computer, and so distributed simulation across multiple computers over the Internet is necessary. In this study, we report our joint effort on developing a spiking brain model and a mouse body model, connecting over the Internet, and conducting bidirectional simulation while synchronizing them.

Optimal dose of intravenous cyclophosphamide during remission induction therapy in ANCA-associated vasculitis: A retrospective cohort study of J-CANVAS.

Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis.

Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model.

PSmad3+/Olig2- expression defines a subpopulation of GFP+/Sox9+ neural progenitors and radial glia-like cells in mouse dentate gyrus through embryonic and postnatal development.

In mouse dentate gyrus, radial glia-like cells (RGLs) persist throughout life and play a critical role in the generation of granule neurons. A large body of evidence has shown that the combinatorial expression of transcription factors (TFs) defines cell types in the developing central nervous system (CNS). As yet, the identification of specific TFs that exclusively define RGLs in the developing mouse dentate gyrus (DG) remains elusive.

An AsCas12f-based compact genome-editing tool derived by deep mutational scanning and structural analysis.

SpCas9 and AsCas12a are widely utilized as genome-editing tools in human cells. However, their relatively large size poses a limitation for delivery by cargo-size-limited adeno-associated virus (AAV) vectors. The type V-F Cas12f from Acidibacillus sulfuroxidans is exceptionally compact (422 amino acids) and has been harnessed as a compact genome-editing tool.

Anti-Glycolipid Antibody Examination in Five EAE Models and Theiler's Virus Model of Multiple Sclerosis: Detection of Anti-GM1, GM3, GM4, and Sulfatide Antibodies in Relapsing-Remitting EAE.

Anti-glycolipid antibodies have been reported to play pathogenic roles in peripheral inflammatory neuropathies, such as Guillain-Barré syndrome. On the other hand, the role in multiple sclerosis (MS), inflammatory demyelinating disease in the central nervous system (CNS), is largely unknown, although the presence of anti-glycolipid antibodies was reported to differ among MS patients with relapsing-remitting (RR), primary progressive (PP), and secondary progressive (SP) disease courses. We investigated whether the induction of anti-glycolipid antibodies could differ among experimental MS models with distinct clinical courses, depending on induction methods.

Detection of the Vesical Arteries Using Three-dimensional Digital Subtraction Angiography Relevant to Intra-arterial Infusion Chemotherapy for Bladder Cancer Using Double-balloon Catheters.

Purpose: This study aims to assess and measure the origin of the superior vesical artery and its distance from the anterior trunk of the internal iliac artery, to which the anticancer drug is infused via double-balloon-occluded arterial infusion bladder-preserving therapy for locally invasive bladder cancer.

Material And Methods: The 160 pelvic sides of 80 patients were analyzed. Double-balloon catheters were bilaterally introduced into the contralateral superior gluteal artery via the internal iliac arteries using a bilateral transfemoral approach.

A Novel Orthognathic Surgery With a Half-Millimeter Accuracy for the Maxillary Positioning Using Prebent Plates and Computer-Aided Design and Manufacturing Osteotomy Guide.

This retrospective study aimed to assess the accuracy of prebent plates and computer-aided design and manufacturing osteotomy guide for orthognathic surgery. The prebent plates correspondent to the planning model were scanned with a 3-dimensional printed model for guide design and used for fixation. Forty-two patients who underwent bimaxillary orthognathic surgery using computer-aided design and manufacturing intermediate splint with the guide (guided group: 20 patients) or with conventional fixation under straight locking miniplates (SLMs) technique (SLM group: 20 patients) were analyzed.

Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model.

COVID-19, caused by SARS-CoV-2 infection, is currently among the most important public health concerns worldwide. Although several effective vaccines have been developed, there is an urgent clinical need for effective pharmaceutical treatments for treatment of COVID-19. Ivermectin, a chemical derivative of avermectin produced by Streptomyces avermitilis, is a macrocyclic lactone with antiparasitic activity.