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.
View Article and Find Full Text PDFBackground: We previously reported the relationship between first-pass pulmonary vein isolation (FPI) and pulmonary vein isolation (PVI) durability in ablation index-guided atrial fibrillation ablation. Obesity is a worsening factor for atrial tachyarrhythmia (AT) recurrence. However, the impact of obesity on FPI has been scarcely reported.
View Article and Find Full Text PDFAs our understanding of ophthalmic optics and visual function advances, the intersection between clinical practice and technological innovation becomes increasingly significant in enhancing patient outcomes [...
View Article and Find Full Text PDFSystemic administration of Janus kinase (JAK) inhibitors is effective in treating chronic graft-versus-host disease (cGVHD) but is associated with side effects. Topical drug administration effectively minimizes side effects. We aimed to investigate potential trends of the efficacy of topical delgocitinib administration in a mouse model.
View Article and Find Full Text PDFOptimal decision-making requires consideration of internal and external contexts. Biased decision-making is a transdiagnostic symptom of neuropsychiatric disorders. We created a computational model demonstrating how the striosome compartment of the striatum constructs a context-dependent mathematical space for decision-making computations, and how the matrix compartment uses this space to define action value.
View Article and Find Full Text PDFBackground: The development of chimeric antigen receptor (CAR)-T cell therapies for solid tumors has attracted considerable attention, yet their clinical efficacy remains limited. Therefore, various efforts have been made to improve the efficacy of CAR-T cell therapy. As one promising strategy, incorporating the T-cell receptor (TCR) machinery into CAR structures has been reported to improve the efficacy of CAR-T cells in studies using conventional CARs targeting such as EGFR.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
November 2024
Purpose: The purpose of this study was to investigate biologically meaningful endotypes of open-angle glaucoma (OAG) by applying unsupervised machine learning to plasma metabolites.
Methods: This retrospective longitudinal cohort study enrolled consecutive patients aged ≥20 years with OAG at Tohoku University Hospital from January 2017 to January 2020. OAG was confirmed based on comprehensive ophthalmic examinations.
Purpose: This study explores the application of adipose-derived mesenchymal stromal cells (adMSCs) as a therapy for ocular inflammatory diseases utilizing a chronic GVHD model.
Methods: Human adMSCs were administered via subconjunctival injection into mice with chronic ocular GVHD. Clinical scores and changes in T cell populations were analyzed.
Methods Mol Biol
November 2024
Base editors, CRISPR/Cas-based precise genome editing tools, enable base conversion at a target site without inducing DNA double-strand breaks. The genome editing targetable range is restricted by the requirement for protospacer adjacent motif (PAM) sequence. Cas9 derived from Streptococcus pyogenes (SpCas9)-most widely used for genome editing in many organisms-requires an NGG sequence adjacent to the target site as a PAM.
View Article and Find Full Text PDFThis retrospective study compared postoperative prediction errors of recent formulas using standard- or total keratometry (K or TK) for intraocular lens (IOL) power calculation in post-myopic LASIK patients. It included 56 eyes of 56 patients who underwent uncomplicated cataract surgery, with at least 1-month follow-up at Keio University Hospital in Tokyo or Hayashi Eye Hospital in Yokohama, Japan. Prediction errors, absolute errors, and percentage of eyes with prediction errors within ± 0.
View Article and Find Full Text PDFPurpose: The topical administration of spironolactone, a mineralocorticoid receptor antagonist (MRA) improves dry eye symptoms in patients with ocular graft-versus-host disease (GVHD); however, the detailed mechanism remains unclear. This study aimed to investigate the effects of spironolactone eyedrops on the ocular surface using a chronic GVHD (cGVHD) mouse model and to determine the expression of the mineralocorticoid receptor (MR).
Methods: A cGVHD mouse model was established by allogeneic bone marrow transplantation (BMT) from B10.
Background: Alcohol use, especially at high consumption levels, can lead to irrational decision-making. In humans, this can lead to harmful outcomes often seen in the context of driving under the influence and or aggressive behavior. To date, the field is lacking comprehensive animal models to examine the impact of alcohol use on decision making in rodents, particularly to examine sex differences in choice behavior.
View Article and Find Full Text PDFMyopia is a global public health concern, with a higher prevalence in women than that in male. As the relationship between sex hormone and myopia remains unclear, we aimed to reveal the relationship between sex hormone and myopia by removing the ovaries of mice and measuring changes in ocular parameters related to myopia. Lens-induced myopia (LIM) surgeries were performed on 3-week-old male mice and age-matched female mice to evaluate the effects of sex on myopia development, which indicated a high degree of myopia and rapid progression of axial elongation in male mice.
View Article and Find Full Text PDFHypoxia-inducible factors (HIFs) are transcriptional factors that function as strong regulators of oxygen homeostasis and cellular metabolisms. The maintenance of cellular oxygen levels is critical as either insufficient or excessive oxygen affects development and physiologic and pathologic conditions. In the eye, retinas have a high metabolic demand for oxygen.
View Article and Find Full Text PDFPathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.
View Article and Find Full Text PDFClin Optom (Auckl)
September 2024
Purpose: Risk factors for presbyopia have not been fully determined although previous studies suggested presbyopia was associate with age, dry eye, and retinal ganglion cell complex thickness (GCC). We accessed these signs and common ocular symptoms in the middle-aged population focusing on sex differences when women have drastic hormonal change.
Methods: This cohort study consecutively enrolled 2743 patients aged 36-45 years (n=1000), 46-55 years (n=1000), and 56-65 years (n=743).
JACC Cardiovasc Imaging
October 2024
Aims: The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging based on resting assessments. Exercise echocardiography is often used to unmask abnormalities that develop during exercise, but the diagnostic criteria have not been standardized. This study aimed to elucidate how cardiologists utilize exercise echocardiography to diagnose HFpEF in real-world practice.
View Article and Find Full Text PDFBackground And Aims: The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF.
Methods: Strain surveillance during chemotherapy for improving cardiovascular outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites.
Purpose: There is limited evidence to evaluate the numerical cutoff point for detecting early presbyopia. Thus, we aimed to establish a clinically relevant optimal cutoff value of near visual acuity for detecting early presbyopia.
Study Design: Prospective diagnostic accuracy study.
Unlabelled: Decision-making requires continuous adaptation to internal and external contexts. Changes in decision-making are reliable transdiagnostic symptoms of neuropsychiatric disorders. We created a computational model demonstrating how the striosome compartment of the striatum constructs a mathematical space for decision-making computations depending on context, and how the matrix compartment defines action value depending on the space.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
August 2024