A 7-year delayed diagnosis in a case of spinal muscular atrophy.

Background: Most cases of spinal muscular atrophy (SMA) can be diagnosed by copy number analysis of survival motor neuron (SMN) 1. However, a small number of cases of SMA can only be diagnosed by sequencing analysis. We present a case of SMA diagnosed 7 years after the onset of symptoms.

Opportunities for microphysiological systems from the view of Japanese industries.

Regulatory authorities and pharmaceutical companies in Europe and the United States have paid attention to microphysiological systems (MPS), and various consortia and academic societies have been established. They are actively working toward their implementation under individual company or regulatory acceptance. In Japan, some AMED projects, academic societies, and consortia have also been established and activities have begun.

Advancements in Microphysiological systems: Exploring organoids and organ-on-a-chip technologies in drug development -focus on pharmacokinetics related organs.

This study explored the evolving landscape of Microphysiological Systems (MPS), with a focus on organoids and organ-on-a-chip (OoC) technologies, which are promising alternatives to animal testing in drug discovery. MPS technology offers in vitro models with high physiological relevance, simulating organ function for pharmacokinetic studies. Organoids composed of 3D cell aggregates and OoCs mimicking in vivo environments based on microfluidic platforms represent the forefront of MPS.

Development and application of 3D cardiac tissues derived from human pluripotent stem cells.

Recently human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate drug responses for cardiotoxicity testing and disease modeling. Moreover, three-dimensional (3D) cardiac models, such as engineered heart tissues (EHTs) developed by bioengineering approaches, and cardiac spheroids (CSs) formed by spherical aggregation of hPSC-CMs, have been established as useful tools for drug discovery and transplantation. These 3D models overcome many of the shortcomings of conventional 2D hPSC-CMs, such as immaturity of the cells.

Global expansion of microphysiological systems (MPS) and Japan's initiatives: Innovation in pharmaceutical development and path to regulatory acceptance.

Microphysiological systems (MPS) are gaining global attention as potential game-changers in pharmaceutical development. Since 2013, MPS suppliers from university laboratories in the United States and Europe have competed to develop these devices. After the development phase, the focus shifted to the accumulation of applications using MPS for pharmaceutical companies and end users.

Development of intestinal organoids and microphysiological systems and their application to drug discovery.

The intestines are an important organ with a variety of functions. For drug discovery research, experimental animals and Caco-2 cells derived from a human colon carcinoma may be used to evaluate the absorption and safety of orally administered drugs. These systems have issues, such as species differences with humans in experimental animals, variations in gene expression patterns, very low drug-metabolizing activities in Caco-2 cells, and the recent trend toward reduced animal testing.

Micro-physiological system of human lung: The current status and application to drug discovery.

Various attempts have been made to elucidate the mechanisms of human lung development, its physiological functions, and diseases, in the hope of new drug discovery. Recent technological advancements in experimental animals, cell culture, gene editing, and analytical methods have provided new insights and therapeutic strategies. However, the results obtained from animal experiments are often inconsistent with those obtained from human data because of reproducibility issues caused by structural and physiological differences between mice and humans.

Organoids and microphysiological systems for pharmaceutical research of viral respiratory infections.

In the pharmaceutical research of viral respiratory infections, cell culture models have traditionally been used to evaluate the therapeutic effects of candidate compounds. Although cell lines are easy to handle and cost-effective, they do not fully replicate the characteristics of human respiratory organs. Recently, organoids and microphysiological systems (MPS) have been employed to overcome this limitation for in vitro testing of drugs against viral respiratory infections.

Multi-SpinX: An advanced framework for automated tracking of mitotic spindles and kinetochores in multicellular environments.

SpinX, an AI-guided spindle tracking software, allows the 3-dimensional (3D) tracking of metaphase spindle movements in mammalian cells. Using over 900 images of dividing cells, we create the Multi-SpinX framework to significantly expand SpinX's applications: a) to track spindles and cell cortex in multicellular environments, b) to combine two object tracking (spindle with kinetochores marked by centromeric probes) and c) to extend spindle tracking beyond metaphase to prometaphase and anaphase stages where spindle morphology is different. We have used a human-in-the-loop approach to assess our optimisation steps, to manually identify challenges and to build a robust computational pipeline for segmenting kinetochore pairs and spindles.

Co-precipitating calcium phosphate as oral detoxification of cadmium.

Bone-eating (also known as osteophagia), found in wild animals, is primarily recognized as a means to supplement phosphorus and calcium intake. Herein, we describe a novel function of bone-eating in detoxifying heavy metal ions through the dissolution and co-precipitation of bone minerals as they travel through the gastrointestinal (GI) tract. In this study, cadmium (Cd), a heavy metal ion, served as a toxic model.

New treatments for adult T-cell leukemia/lymphoma.

Adult T cell leukemia lymphoma (ATL) is a mature T cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). ATL is endemic in specific geographic regions of the world closely related to areas with high prevalence of HLTV-1 infection, including Southwestern Japan, the Caribbean Basin, Central Africa, South America, Northern and Central Australia. HLTV-1 is primarily transmitted through breastmilk in asymptomatic carriers with a long latency period before transformation into ATL in 3 - 5 % of carriers after acquisition of multiple leukemogenic mutations.

Cognitive assessment in patients with acute stroke: Exploring early intervention for dementia.

Background: Early detection of cognitive impairment in patients with acute stroke could improve dementia treatment; however, such testing is uncommon. This study aimed to assess cognitive testing feasibility in patients with acute stroke and identify patient characteristics associated with testing ability.

Methods: 291 patients with suspected acute stroke were admitted to our hospital between December 2016 and May 2017.

Evidence for successful gastric perfusion computed tomography with low-radiation dose.

Objective: To investigate how the blood flow analysis changes by varying the radiation dose of gastric perfusion CT (PCT) and to prove that a low-radiation dose of PCT is feasible.

Methods: 5 Beagle dogs were used in a crossover study with 6 groups of varying radiation doses. Iodixanol was IV administered at 3.

Quantitative Evaluation of 99mTc-Galactosyl Human Serum Albumin SPECT/CT for the Prediction of Posthepatectomy Liver Failure.

Purpose: To evaluate the predictive ability of 99mTc-galactosyl human serum albumin SPECT/CT quantitative parameters for posthepatectomy liver failure (PHLF).

Methods: Sixty-eight patients who underwent 99mTc-galactosyl human serum albumin scintigraphy as a preoperative examination for hepatectomy between July 2021 and December 2023 were prospectively evaluated. The patients were divided into PHLF and non-PHLF groups.

Treatment of Focal Thoracic Ossification of the Ligamentum Flavum by Percutaneous Posterolateral Transforaminal Endoscopic Surgery Under Local Anesthesia: A Case Series Study.

Introduction: Minimally invasive techniques, such as percutaneous endoscopic discectomy, are increasingly utilized for treating focal thoracic ossification of the ligamentum flavum (TOLF), where their safety and efficacy needs to be further confirmed. The purpose of this study was to investigate the safety and efficacy of percutaneous posterolateral transforaminal endoscopic surgery under local anesthesia for treating focal TOLF.

Methods: This case series study reviewed medical records of 12 cases diagnosed with focal TOLF who underwent percutaneous posterolateral transforaminal endoscopic surgery under local anesthesia from December 2016 to July 2019 at Fuzhou Second Hospital.

Claudins as diagnostic tools and therapeutic targets-Glimpse of the horizon.

Claudins (CLDNs) play a crucial and indispensable role as fundamental components within the structure of tight junctions. Due to the distinct and unique distribution pattern exhibited by CLDNs in both normal and malignant tissues, these proteins have garnered significant attention as pivotal targets for systemic anti-cancer therapy and as noteworthy diagnostic markers. This review provides a comprehensive and detailed elucidation of the fundamental understanding surrounding CLDNs, their intricate expression patterns, the potential role they play in cancer diagnosis and therapeutic potentials; all encapsulated within a succinct summary of the cutting-edge advancements and the information derived from various clinical trials.

Light-Harvesting Spin Hyperpolarization of Organic Radicals in a Metal-Organic Framework.

Light-driven spin hyperpolarization of organic molecules is a crucial technique for spin-based applications such as quantum information science (QIS) and dynamic nuclear polarization (DNP). Synthetic chemistry provides the design of spins with atomic precision and enables the scale-up of individual spins to hierarchical structures. The high designability and extended pore structure of metal-organic frameworks (MOFs) can control interactions between spins and guest molecules.

Effectiveness of Oral Prophylactic Antibiotics for Diagnostic Bronchoscopy: A Nationwide Database Study.

Rationale: Although the guidelines generally omit routine antibiotic prophylaxis for diagnostic bronchoscopy, this recommendation is primarily based on studies with relatively small sample sizes conducted at single institutions. Moreover, the applicability of recent technical and procedural advancements to these guidelines remains uncertain.

Objectives: To evaluate whether oral prophylactic antibiotic administration for diagnostic bronchoscopy reduces post-bronchoscopy infections among non-infectious diseases in the current setting.

Mpox drug wins approval in Japan-but it doesn't work.

Europe previously approved tecovirimat for mpox, based on animal data; the U.S. has stockpiled it for smallpox.

DECODE enables high-throughput mapping of antibody epitopes at single amino acid resolution.

Antibodies are extensively used in biomedical research, clinical fields, and disease treatment. However, to enhance the reproducibility and reliability of antibody-based experiments, it is crucial to have a detailed understanding of the antibody's target specificity and epitope. In this study, we developed a high-throughput and precise epitope analysis method, DECODE (Decoding Epitope Composition by Optimized-mRNA-display, Data analysis, and Expression sequencing).

Comparison of actionable alterations in cancers with kinase fusion, mutation, and copy number alteration.

Kinase-related gene fusion and point mutations play pivotal roles as drivers in cancer, necessitating optimized, targeted therapy against these alterations. The efficacy of molecularly targeted therapeutics varies depending on the specific alteration, with great success reported for such therapeutics in the treatment of cancer with kinase fusion proteins. However, the involvement of actionable alterations in solid tumors, especially regarding kinase fusions, remains unclear.

Preparation of Hydroxyapatite-Aligned Collagen Sheets and Their Evaluation for Fibroblast Adhesion and Collagen Secretion.

The structure of many native tissues consists of aligned collagen (Col) fibrils, some of which are further composited with dispersed hydroxyapatite (HAp) nanocrystals. Accurately mimicking this inherent structure is a promising approach to enhance scaffold biocompatibility in tissue engineering. In this study, biomimetic sheets composed of highly aligned Col fibrils were fabricated using a plastic compression and tension method, followed by the deposition of HAp nanocrystals on the surface via an alternate soaking method.

Characteristics and treatment patterns in patients with multiple myeloma in Japan: A retrospective cohort analysis.

Background: Approval of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies (mAbs), such as daratumumab, has reshaped treatment patterns in patients with multiple myeloma (MM) in Japan. This retrospective study evaluated patient characteristics, treatment patterns, and trends in MM patients using Medical Data Vision, the largest electronic health records database in Japan with anonymous inpatient and outpatient health information.

Methods: Patients aged ≥18 years, with ≥2 records of an MM diagnostic and disease code and ≥1 record of MM treatment between 01 April 2008 and 30 June 2023 were included.