Mutation Analysis of TMB-High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications.

Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed.

Efficacy of anifrolumab on systemic lupus erythematosus patients with serological manifestations: A post hoc analysis of the Japan subgroup of the TULIP-2 Trial.

Objectives: To describe the efficacy of anifrolumab vs. placebo in Japanese systemic lupus erythematosus (SLE) patients with low complement (C3 or C4) and/or who are positive for anti-double stranded DNA (anti-dsDNA) antibodies.

Methods: This was a descriptive post hoc analysis of Japanese SLE patients with serological manifestations in the TULIP-2 trial who received either anifrolumab or placebo.

2024 Update of the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis - secondary publication.

Objectives: To update the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis (CPG for RA).

Methods: The recommendations were developed based on the evidence published until the end of June 2022 using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The steering committee, CPG panel, systematic review (SR) group, and SR support team were organised.

Spirometry estimation of central airway dysanapsis on computed tomography in healthy subjects without active lung diseases.

The original concept of the airway-to-lung size mismatch, termed dysanapsis, was introduced on spirometry and was extended by computed tomography (CT) evaluation of the central airways. CT-assessed dysanapsis allows a risk estimation of lung disease development in healthy subjects, although radiation exposure limits its use, particularly for younger subjects. This study investigated which spirometry indices can be used to estimate CT-assessed central airway dysanapsis in healthy subjects.

Anatomical analysis of the periosteal blood supply system of the fibula using fresh cadavers.

A vascularized free fibula flap is often used to reconstruct bone defects. However, bone resorption within the osteotomized segment is often observed. This may be attributed to damage to bone blood flow supplied by nonpenetrating periosteal vessels (NPPVs); however, there are few studies on NPPVs in the fibula.

First-line pembrolizumab-axitinib versus sunitinib in metastatic RCC: subgroup analysis of patients enrolled in the phase 3 KEYNOTE-426 in Eastern Asia.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).

Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off).

Recent trends in scientific research in chest radiology: What to do or not to do? That is the critical question in research.

Hereby inviting young rising stars in chest radiology in Japan for contributing what they are working currently, we would like to show the potentials and directions of the near future research trends in the research field. I will provide a reflection on my own research topics. At the end, we also would like to discuss on how to choose the themes and topics of research: What to do or not to do? We strongly believe it will stimulate and help investigators in the field.

Ethical considerations regarding the treatment of extremely preterm infants at the limit of viability: a comprehensive review.

Advancements in perinatal care have improved survival rates of extremely preterm infants born at 22 to 23 weeks of gestation, thus introducing new ethical challenges associated with their treatment. Therefore, we reviewed the epidemiological prognosis, treatment evolution, and ethical considerations associated with the care of preterm infants at the limit of viability. We comprehensively searched PubMed to find relevant English-language articles published between January 2014 and July 2024.

Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring.

Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation.

Novel triangle papilla access approach for interdental bone defect regeneration: A case study.

Background: Successful periodontal regeneration depends on primary wound closure and interdental papilla preservation. In this case study, we introduce a novel triangle papilla access approach (T-PAA) performed under a surgical microscope for treating interdental bone defects. In this novel approach, buccal incisions were used to access root surfaces and bone defects, avoiding interdental papilla incisions and preventing papillary collapse and necrosis.

-A152T mutation drives neuronal hyperactivity through Fyn-NMDAR signaling in human iPSC-Derived neurons: Insights into Alzheimer's pathogenesis.

Introduction: Tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and in regulating neuronal excitability. Among tau-coding microtubule associated protein tau () gene mutations, the A152T mutation is reported to increase the risk of AD and neuronal excitability in mouse models.

Methods: To investigate the effects of gene expression and its mutations on neuronal activity in human neurons, we employed genome editing technology to introduce the A152T or P301S mutations into induced pluripotent stem cells (iPSCs).

Empirical design of population health strategies accounting for the distribution of population health risks.

Recent discussions in epidemiology have emphasised the need to estimate the heterogeneous effects of risk factors across the distribution of health outcomes for better aetiological understanding of the determinants of population health. We propose using quantile regression-based decomposition to expand the empirical discussion on population health intervention strategies for health equity by incorporating population homogeneity/heterogeneity in the risk-outcome association. We theorised that the 'proportionate universalism' approach presumes population homogeneity in the risk-outcome association with varying risk intensities, which decomposition analysis shows as the 'covariates part' between groups.

-Linked Parkinson Syndrome in Female Heterozygotes Is Associated With PET-Detectable Tau Pathology.

Background And Objectives: A previous postmortem study of men with Christianson syndrome, a disorder caused by loss-of-function mutations in the gene , reported a mechanistic link between pathologic tau accumulation and progressive symptoms such as cerebellar atrophy and cognitive decline. This study aimed to characterize the relationships between neuropathologic manifestations and tau accumulation in heterozygous women with mutation.

Methods: We conducted a multimodal neuroimaging and plasma biomarker study on 3 middle-aged heterozygous women with mutations (proband 1: mid-50s; proband 2: early 50s; proband 3: mid-40s) presenting with progressive extrapyramidal symptoms.

Creatinine production rate is an integrative indicator to monitor muscle status in critically ill patients.

Background: Both quantitative and qualitative aspects of muscle status significantly impact clinical outcomes in critically ill patients. Comprehensive monitoring of baseline muscle status and its changes is crucial for risk stratification and management optimization. However, repeatable and accessible indicators are lacking.

A first-in-human clinical study of an allogenic iPSC-derived corneal endothelial cell substitute transplantation for bullous keratopathy.

A first-in-human investigator-initiated clinical study of a corneal endothelial cell substitute (CLS001) derived from a clinical-grade induced pluripotent stem cell (iPSC) line shows improvement of visual acuity and corneal stromal edema, with no adverse events for up to 1 year after surgery for the treatment of bullous keratopathy. While preclinical tests, including multiple whole-genome analysis and tumorigenicity tests adhering to the Food and Drug Administration (FDA) draft guidelines, are negative, an additional whole-genome analysis conducted on transplanted CLS001 cells reveals a de novo in-frame deletion of exon22 in the EP300 gene. No adverse events related to the mutation are observed.

Electronic Patient-Reported Outcome System Implementation in Outpatient Cardiovascular Care: A Randomized Clinical Trial.

Importance: The integration of patient-reported outcome (PRO) assessments in cardiovascular care has encountered considerable obstacles despite their established clinical relevance.

Objective: To assess the impact of a physician- and patient-friendly electronic PRO (ePRO) monitoring system on the quality of cardiovascular care in clinical practice.

Design, Setting, And Participants: This open-label, multicenter, pilot randomized clinical trial was phase 2 of a multiphase study that was conducted from October 2022 to October 2023 and focused on the implementation and evaluation of an ePRO monitoring system in outpatient clinics in Japan.

Tenascin-X deficiency causing classical-like Ehlers Danlos syndrome type 1 in humans is a significant risk factor for GI and tracheal ruptures.

Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of Ehlers Danlos Syndrome (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX is an extracellular matrix protein needed for collagen stability. Previous publications propose that individuals with clEDS1 might be at risk for gastrointestinal (GI) tract perforations and/or tracheal ruptures.

HIF1α Plays a Crucial Role in the Development of TFE3-Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis.

Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α.

Significance of Endoscopic Redness of Duodenum in Health Checkup.

Background And Aim: It is important for endoscopist to diagnose the lesion redness. In this study, we focused on the redness of duodenal bulb. We objectively analyzed the changes in redness of the duodenal bulb using linked color imaging (LCI) with chromatic indicators.

ENDOTHELIAL PROX1 INDUCES BLOOD-BRAIN BARRIER DISRUPTION IN THE CENTRAL NERVOUS SYSTEM.

The central nervous system (CNS) parenchyma has conventionally been believed to lack lymphatic vasculature, likely due to a non-permissive microenvironment that hinders the formation and growth of lymphatic endothelial cells (LECs). Recent findings of ectopic expression of LEC markers including Prospero Homeobox 1 (PROX1), a master regulator of lymphatic differentiation, and the vascular permeability marker Plasmalemma Vesicle Associated Protein (PLVAP), in certain glioblastoma and brain arteriovenous malformations (AVMs), has prompted investigation into their roles in cerebrovascular malformations, tumor environments, and blood-brain barrier (BBB) abnormalities. To explore the relationship between ectopic LEC properties and BBB disruption, we utilized endothelial cell-specific overexpression mutants.

Asian Pacific Society of Cardiology Position Statement on the Use of Transcatheter Aortic Valve Implantation in the Management of Aortic Stenosis.

Transcatheter aortic valve implantation (TAVI) has been established as an effective treatment modality in patients with severe aortic stenosis (AS) and the uptake of TAVI is rapidly growing in the Asia-Pacific region. However, there exist a heterogeneity in the management of aortic stenosis and the use of TAVI among countries in the region. Reasons for these differences include anatomic variations, disparity in healthcare resources and infrastructure, and the lack of consensus on the optimal management of AS in the Asia-Pacific region.