Recent advances in identifying and characterizing secretory proteins of Toxoplasma gondii by CRISPR-based screening.

The apicomplexan parasite, Toxoplasma gondii, develops unique secretory organelles, such as micronemes, rhoptries, and dense granules, which do not exist in other well-studied eukaryotic organisms. These secretory organelles are key features of apicomplexan parasites and discharge various proteins that are essential for invasion, replication, egress, host-parasite interactions, and virulence. Many studies have therefore focused on identifying and characterizing the proteins secreted by T.

Significantly smaller lateral extrusion was observed within 24 weeks after all-inside suture repairs of radial tear in the middle segment of lateral meniscus compared to inside-out repairs.

Purpose: To evaluate the postoperative meniscal extrusion between all-inside suture (AIS) and trans-capsular suture (TCS) repair techniques.

Methods: Thirteen patients (mean age, 19.4 years) underwent AIS repairs using only sutures (AIS group) for radial tears in the middle segment of the lateral meniscus (RTMLM), and seven patients (mean age, 20.

Depth of response and treatment outcomes of immune checkpoint inhibitor-based therapy in patients with advanced non-small cell lung cancer and high PD-L1 expression: An exploratory analysis of retrospective multicenter cohort.

The association between depth of response (DpR) and treatment outcomes has been documented across various types of cancer. Immune checkpoint inhibitor (ICI)-based treatment is globally used as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥ 50%. However, in this population, the significance of DpR is not elucidated.

CRISPR screens identify genes essential for virulence among proteins of hyperLOPIT-unassigned subcellular localization in .

The research field to identify and characterize genes essential for virulence in has been dramatically advanced by a series of clustered regularly interspaced short palindromic repeats (CRISPR) screens. Although subcellular localizations of thousands of proteins were predicted by the spatial proteomic method called hyperLOPIT, those of more than 1,000 proteins remained unassigned, and their essentiality in virulence was also unknown. In this study, we generated two small-scale gRNA libraries targeting approximately 600 hyperLOPIT-unassigned proteins and performed CRISPR screens.

Triple combination therapy comprising osimertinib, an AXL inhibitor, and an FGFR inhibitor improves the efficacy of EGFR-mutated non-small cell lung cancer.

We previously reported that combined therapy with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) osimertinib and AXL inhibitor ONO-7475 is effective in preventing the survival of drug-tolerant cells in high-AXL-expressing EGFR-mutated non-small cell lung cancer (NSCLC) cells. Nevertheless, certain residual cells are anticipated to eventually develop acquired resistance to this combination therapy. In this study, we attempted to establish a multidrug combination therapy from the first-line setting to overcome resistance to this combination therapy in high-AXL-expressing EGFR-mutated NSCLC.

High prevalence of hepatitis C virus among criminals in rehabilitation facilities in Japan.

Objective: There is a high prevalence of hepatitis C virus (HCV) carriers in prison in several developed countries, but the situation in Japan has not been well reported. This study aimed to determine the state of HCV infection among criminals in Japan.

Methods: We enrolled 533 criminals in rehabilitation facilities (354 men and 179 women) who underwent a medical check-up from April 2014 to March 2022.

Assessment of P-glycoprotein function using canine intestinal organoid-derived epithelial interfaces.

P-glycoprotein (P-gp), a multidrug efflux pump encoded by the (formerly ) gene, plays a crucial role in limiting drug absorption and eliminating toxic compounds in both humans and dogs. However, species-specific differences in P-gp substrates necessitate the development of canine-specific evaluation systems. Canine intestinal organoids derived monolayers offer a promising platform for studying drug transport, yet P-gp-mediated transport in these models remains unexplored.

Squamous metaplasia is an indicator of acute exacerbation in patients with usual interstitial pneumonia / idiopathic pulmonary fibrosis.

Background: Acute exacerbation (AE) is a potentially lethal event in patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF). However, to date, no pathological predictors of AE have been identified. This retrospective study aimed to elucidate the pathological features that could predict AE in patients with UIP.

Validation of prostate and breast cancer detection artificial intelligence algorithms for accurate histopathological diagnosis and grading: a retrospective study with a Japanese cohort.

Prostate and breast cancer incidence rates have been on the rise in Japan, emphasising the need for precise histopathological diagnosis to determine patient prognosis and guide treatment decisions. However, existing diagnostic methods face numerous challenges and are susceptible to inconsistencies between observers. To tackle these issues, artificial intelligence (AI) algorithms have been developed to aid in the diagnosis of prostate and breast cancer.

Nationwide data from comprehensive genomic profiling assays for detecting driver oncogenes in non-small cell lung cancer.

Driver oncogenes are investigated upfront at diagnosis using multi-CDx systems with next-generation sequencing techniques or multiplex reverse-transcriptase polymerase chain reaction assays. Additionally, from 2019, comprehensive genomic profiling (CGP) assays have been available in Japan for patients with advanced solid tumors who had completed or were expected to complete standard chemotherapy. These assays are expected to comprehensively detect the driver oncogenes, especially for patients with non-small cell lung cancer (NSCLC).

Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of coronavirus disease 2019 (COVID-19) and continues to be a major health concern worldwide. Strategies to protect individuals at high risk of COVID-19 are critical but are currently a largely unmet need. We evaluated the oral antiviral drug ensitrelvir, which specifically targets the SARS-CoV-2 3CL protease, for its efficacy as a pre-exposure prophylactic treatment.

Machine-Learning-Based Classification Model to Address Diagnostic Challenges in Transbronchial Lung Biopsy.

Background: When obtaining specimens from pulmonary nodules in TBLB, distinguishing between benign samples and mis-sampling from a tumor presents a challenge. Our objective is to develop a machine-learning-based classifier for TBLB specimens.

Methods: Three pathologists assessed six pathological findings, including interface bronchitis/bronchiolitis (IB/B), plasma cell infiltration (PLC), eosinophil infiltration (Eo), lymphoid aggregation (Ly), fibroelastosis (FE), and organizing pneumonia (OP), as potential histologic markers to distinguish between benign and malignant conditions.

AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells.

Recently, novel Kirsten rat sarcoma viral oncogene homolog (KRAS) inhibitors have been clinically developed to treat KRAS G12C-mutated non-small cell lung cancer (NSCLC) patients. However, achieving complete tumor remission is challenging. Therefore, the optimal combined therapeutic intervention with KRAS G12C inhibitors has a potentially crucial role in the clinical outcomes of patients.

15-Hydroxyeicosatrienoic acid induces nasal congestion by changing vascular functions in mice.

Background: Nasal congestion in allergic rhinitis (AR) is caused by vascular hyperpermeability and vascular relaxation of the nasal mucosa. We previously detected high levels of a lipoxygenation metabolite of dihomogammalinolenic acid, 15-hydroxy-8Z,11Z,13E-eicosatrienoic acid (15-HETrE) in the nasal lavage fluid of AR model mice. Here, we investigated the effects of 15-HETrE on vascular functions associated with nasal congestion.

Deep-learning reconstruction with low-contrast media and low-kilovoltage peak for CT of the liver.

Aim: To compare images using reduced CM, low-kVp scanning and DLR reconstruction with conventional images (no CM reduction, normal tube voltage, reconstructed with HBIR. To compare images using reduced contrast media (CM), low kilovoltage peak (kVp) scanning and deep-learning reconstruction (DLR) with conventional image quality (no CM reduction, normal tube voltage, reconstructed with hybrid-type iterative reconstruction method [HBIR protocol]).

Materials And Methods: A retrospective analysis was performed on 70 patients with liver disease and three-phase dynamic imaging using computed tomography (CT) from April 2020 to March 2022 at Oita University Hospital.

Association of Stability and Size of Unhealed Area With Failure After Internal Fixation for Osteochondritis Dissecans Lesions of the Knee: Radiological Evaluation Using Computed Tomography.

Background: Open reduction and internal fixation (ORIF) has been widely performed because the osteochondral component of the osteochondritis dissecans (OCD) lesion is the most suitable for reconstructing the joint structure.

Purpose: To evaluate radiological healing in terms of reconstructed bony structure after ORIF with bone graft by computed tomography (CT), to identify preoperative prognostic factors for failure, and to determine the cutoff value of radiological healing for risk of failure.

Study Design: Case-control study; Level of evidence, 3.

Noise reduction by multiple path neural network using Attention mechanisms with an emphasis on robustness against Errors: A pilot study on brain Diffusion-Weighted images.

Purpose: In deep learning-based noise reduction, larger networks offer advanced and complex functionality by utilizing its greater degree of freedom, but come with increased unpredictability, raising the potential risk of unforeseen errors. Here, we introduce a novel denoising model for diffusion-weighted images that intentionally limits the network output freedom by incorporating multiple pathways with varying degrees of freedom, with the aim of minimizing the chance of unintended alterations to the input. The purpose of this pilot study is to assess the model's ability to perform effective denoising under the constraints.

Peptide-to-Small Molecule: Discovery of Non-Covalent, Active-Site Inhibitors of β-Herpesvirus Proteases.

Viral proteases, the key enzymes that regulate viral replication and assembly, are promising targets for antiviral drug discovery. Herpesvirus proteases are enzymes with no crystallographically confirmed noncovalent active-site binders, owing to their shallow and polar substrate-binding pockets. Here, we applied our previously reported "Peptide-to-Small Molecule" strategy to generate novel inhibitors of β-herpesvirus proteases.

[A case of fascioliasis].

A 38-year-old rice farmer visited a hospital for abdominal pain. Computed tomography (CT) showed a liver tumor and magnetic resonance imaging (MRI) revealed a hypovascular tumor, both in segment 4. Thus, he was diagnosed with liver abscess.

Pharmacokinetic and Pharmacodynamic Analysis of the 3CL Protease Inhibitor Ensitrelvir in a SARS-CoV-2 Infection Mouse Model.

The small-molecule antiviral drug ensitrelvir targets the 3C-like protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study evaluated its inhibitory effect on viral replication in a delayed-treatment mouse model and investigated the relationship between pharmacokinetic (PK) parameters and pharmacodynamic (PD) effects. SARS-CoV-2 gamma-strain-infected BALB/c mice were orally treated with various doses of ensitrelvir starting 24 h post-infection.