Regulatory insights on advanced CAR-T cell products, AAV-based Gene therapies, and medical care/practice in cell and Gene therapies: Report from the 6th Asia partnership conference of regenerative medicine- April 20, 2023.

The 6th Asia Partnership Conference of Regenerative Medicine (APACRM) was held in person with online on April 20, 2023, to promote the regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region and the underlying rationales are important initial steps toward harmonizing regulations. The 6th APACRM featured an open dialog regarding non-clinical evaluation for advanced CAR-T products, regulation of clinical trials for AAV-based gene therapies, and cell and gene therapies provided to patients as medical care/medical practices without market authorization through presentations from the industry and panel discussions with regulatory agencies.

Secretoglobin 3A2 peptides have therapeutic potential for allergic airway inflammation.

Three isoforms of secretoglobin (SCGB) 3A2, namely type A, B, and C, are endogenously produced through alternative splicing. SCGB3A2 type A, the correctly spliced major type, begins to be expressed from embryonic day 11.5 in mice and shows various physiological activities such as promoting lung maturation and bronchial branching, anti-inflammatory effects, and ameliorating induced pulmonary fibrosis.

Posterior Cartilage Endplate Disruption on T1-weighted Magnetic Resonance Imaging as a Predictor for Postoperative Recurrence of Lumbar Disk Herniation.

Study Design: A retrospective cohort study.

Objective: This study aimed to investigate the relationship between disruption of cartilage endplates and postoperative recurrence of lumber disk herniation (LDH) using preoperative T1-weighted magnetic resonance imaging (MRI-T1WI).

Summary Of Background Data: Recurrence of LDH is a relatively common complication after discectomy.

Mortality, Analgesic Use, and Care Requirements After Vertebral Compression Fractures: A Retrospective Cohort Study of 18,392 Older Adult Patients.

Background: Vertebral compression fractures (VCFs) in older adults cause considerable health and socioeconomic burdens due to worsening ability to perform activities of daily living. The long-term effects of VCFs on patient outcomes, particularly prolonged analgesic use and functional decline, remain unknown. The aims of this study were to examine long-term clinical outcomes and to determine the risk factors for persistent pain and functional disability after VCFs.

Calcium transients trigger switch-like discharge of prostaglandin E in an extracellular signal-regulated kinase-dependent manner.

Prostaglandin E (PGE) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin-Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors, we demonstrate that calcium transients in a single cell cause PGE-mediated radial spread of PKA activation (RSPA) in neighboring cells.

Usefulness of the preoperative thoracic inlet angle in comparison to the T1 slope for predicting cervical kyphosis after laminoplasty.

Purpose: Thoracic inlet angle (TIA) is a sagittal radiographic parameter with a constant value regardless of posture and is significantly correlated with the sagittal balance of the cervical spine. However, the practical use of TIA has not been studied. This study aimed to investigate the usefulness of the preoperative TIA for predicting the development of kyphotic deformity after cervical laminoplasty in comparison to the preoperative T1 slope (T1S).

Color vision evolution in egg-laying mammals: insights from visual photoreceptors and daily activities of Australian echidnas.

Egg-laying mammals (monotremes) are considered "primitive" due to traits such as oviparity, cloaca, and incomplete homeothermy, all of which they share with reptiles. Two groups of monotremes, the terrestrial echidna (Tachyglossidae) and semiaquatic platypus (Ornithorhynchidae), have evolved highly divergent characters since their emergence in the Cenozoic era. These evolutionary differences, notably including distinct electrosensory and chemosensory systems, result from adaptations to species-specific habitat conditions.

Reproductive interference between alien species in Veronica.

Reproductive interference can lead to the exclusive distribution of species. Reports on reproductive interference between alien species are scarce, although alien species are becoming more abundant and evaluations of the interference between aliens and its influence on community structure are essential. We therefore investigated the presence of interference in two alien species of Veronica, V.

Refined scan protocol for the evaluation of pulmonary perfusion standardized image quality and reduced radiation dose in dynamic chest radiography.

Purpose: Dynamic chest radiography (DCR) is a novel imaging technique used to noninvasively evaluate pulmonary perfusion. However, the standard DCR protocol, which is roughly adapted to the patient's body size, occasionally causes over- or underexposure, which could influence clinical evaluation. Therefore, we proposed a refined protocol by increasing the number of patient body mass index (BMI) categories from three to seven groups and verified its usefulness by comparing the image sensitivity indicators (S-values) and entrance surface doses (ESDs) of the conventional protocol with those of our refined protocol.

Radiographic Predictors of Subaxial Subluxation After Atlantoaxial Fusion.

Study Design: A retrospective study.

Objective: The aim of this study was to clarify preoperative radiographic predictors associated with the development of subaxial subluxation (SAS) after surgery.

Background: The incidence of atlantoaxial fusion for atlantoaxial instability has been increasing.

Trends in cervical laminoplasty and 30-day postoperative complications: 10-year results from a retrospective, multi-institutional study of 1095 patients.

Purpose: This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications.

Methods: This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications.

Improved Production of Induced Pluripotent Stem Cells Using Dot Pattern Culture Plates.

The rate of cell proliferation is a crucial factor in cell production under good manufacturing practice (GMP) control. In this study, we identified a culture system for induced pluripotent cells (iPSCs) that supports cell proliferation and viability and maintains the cells in an undifferentiated state even at 8 days after seeding. This system involves the use of dot pattern culture plates that have been coated with a chemically defined scaffold which has high biocompatibility.

Performance of dedicated breast PET in breast cancer screening: comparison with digital mammography plus digital breast tomosynthesis and ultrasound.

Objective: To compare the diagnostic performance of dedicated breast positron emission tomography (dbPET) in breast cancer screening with digital mammography plus digital breast tomosynthesis (DM-DBT) and breast ultrasound (US).

Methods: Women who participated in opportunistic whole-body PET/computed tomography cancer screening programs with breast examinations using dbPET, DM-DBT, and US between 2016-2020, whose results were determined pathologically or by follow-up for at least 1 year, were included. DbPET, DM-DBT, and US assessments were classified into four diagnostic categories: A (no abnormality), B (mild abnormality), C (need for follow-up), and D (recommend further examination).

Non-clinical, quality and environmental impact assessments of cell and gene therapy products: Report on the 5th Asia Partnership Conference of Regenerative Medicine - April 7, 2022.

The 5th Asia Partnership Conference of Regenerative Medicine (APACRM) was held online on April 7, 2022 to promote regulatory harmonization of regenerative medicine products throughout Asia. The recognition of domestic regulatory guidelines within each country and region and the underpinning rationales are important initial steps toward the harmonization of regulations. The 5th APACRM featured open dialog regarding non-clinical, quality and environmental impact assessment settings for cell and gene therapy products through presentations from the industry and panel discussions with regulatory agencies.

Smart Gateway for Healthcare Networks Based on Beam Steering Technology.

To ensure high-reliability communication in healthcare networks, this paper presents a smart gateway system that includes an angle-of-arrival (AOA) estimation and a beam steering function for a small circular antenna array. To form a beam toward healthcare sensors, the proposed antenna estimates the direction of the sensors utilizing the radio-frequency-based interferometric monopulse technique. The fabricated antenna was assessed based on the measurements of complex directivity and the over-the-air (OTA) testing in Rice propagation environments using a two-dimensional fading emulator.

Generation of transgenic mice expressing a FRET biosensor, SMART, that responds to necroptosis.

Necroptosis is a regulated form of cell death involved in various pathological conditions, including ischemic reperfusion injuries, virus infections, and drug-induced tissue injuries. However, it is not fully understood when and where necroptosis occurs in vivo. We previously generated a Forster resonance energy transfer (FRET) biosensor, termed SMART (the sensor for MLKL activation by RIPK3 based on FRET), which monitors conformational changes of MLKL along with progression of necroptosis in human and murine cell lines in vitro.

STNM01, the RNA oligonucleotide targeting carbohydrate sulfotransferase 15, as second-line therapy for chemotherapy-refractory patients with unresectable pancreatic cancer: An open label, phase I/IIa trial.

Background: The impact of stroma-targeting therapy on tumor immune suppression is largely unexplored. An RNA oligonucleotide, STNM01, has been shown to repress carbohydrate sulfotransferase 15 (CHST15) responsible for tumor proteoglycan synthesis and matrix remodeling. This phase I/IIa study aimed to evaluate the safety and efficacy of STNM01 in patients with unresectable pancreatic ductal adenocarcinoma (PDAC).

Clinical features, therapeutic outcomes, and recovery period of long COVID.

To characterize the clinical features of long COVID, 286 patients who received care in our outpatient clinic for long COVID from May to December 2021 were surveyed. The recovery periods of each symptom and the key factors contributing to early recovery were statistically analysed. The median age of the patients was 35.

Comparison of guidelines for biological ancillary materials used for the manufacture of gene and cellular therapy products in Asia.

Background Aims: Although biologiocal ancillay materials (AMs) have specific risk associated with their derivations, it plays key role to manufature cell and gene therapy (CGT) products. It is important to understand the regulation relevant to AMs for developers.

Methods: The authors investigated the guidelines and pharmacopeia (hereinafter referred to as "guidelines") for biological AMs used for the manufacture of CGT products in Asia (China, India, Japan, Korea and Taiwan).

Adhesion Characteristics of Human Pancreatic Islets, Duct Epithelial Cells, and Acinar Cells to a Polymer Scaffold.

We reported in 2018 that among several extracellular matrices, fibronectin, type I collagen, type IV collagen, laminin I, fibrinogen, and bovine serum albumin, fibronectin is particularly useful for adhesion of porcine pancreatic tissue. Subsequently, we developed a technology that enables the chemical coating of the constituent motifs of fibronectin onto cell culture dishes. In this experiment, we used islets (purity ≥ 90%), duct epithelial cells (purity ≥ 60%), and acinar cells (purity ≥ 99%) isolated from human pancreas according to the Edmonton protocol published in 2000 and achieved adhesion to the constituent motifs of fibronectin.

Gastric Tube Ulcer that Could Be Saved by Early Conservative Treatment.

The patient was an 81-year-old man who had received subtotal esophagectomy for esophageal cancer reconstructed by a gastric tube via a posterior mediastinal route. He presented to our emergency room with a complaint of epigastric pain and a small amount of hematemesis. Thoracoabdominal computed tomography showed that the reconstructed gastric tube was filled fluid and had irregular wall thickening.

Development of Aging-Related Emphysematous and Lymphoma-Like Lesions is Enhanced by the Lack of Secretoglobin 3A2 in Mouse Lungs.

Background: Secretoglobin (SCGB) 3A2 is a novel bioactive molecule with anti-inflammatory and anti-fibrotic activities. SCGB3A2 also promotes the maturation of bronchial divergence and the lungs during embryonic development. However, much remains unknown concerning the roles of SCGB3A2 in diseases associated with aging.

Neutron imaging with an inertial electrostatic confinement fusion neutron source.

A compact inertial electrostatic confinement (IEC) fusion neutron source was developed. Imaging tests using the cylindrical IEC neutron source were conducted with the indirect imaging plate (IP) method using dysprosium foil and an imaging plate. An array of powder contained in a stainless-steel blade and Cd pins was successfully imaged.

Nonclinical and quality assessment of cell therapy products: Report on the 4th Asia Partnership Conference of Regenerative Medicine, April 15, 2021.

The 4th Asia Partnership Conference of Regenerative Medicine (APACRM) was held online on April 15, 2021, to promote regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region, and their underpinning rationales, is an important initial step toward a convergence of regulations. The 4th APACRM consisted of an open dialog with regulatory agencies regarding nonclinical and quality settings for cell therapy products (CTPs) through industry presentations and panel discussions with regulatory agencies.

A chemically-defined plastic scaffold for the xeno-free production of human pluripotent stem cells.

Clinical use of human pluripotent stem cells (hPSCs) is hampered by the technical limitations of their expansion. Here, we developed a chemically synthetic culture substrate for human pluripotent stem cell attachment and maintenance. The substrate comprises a hydrophobic polyvinyl butyral-based polymer (PVB) and a short peptide that enables easy and uniform coating of various types of cell culture ware.