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.

Epoxide hydrolases JHEH1 and JHEH2 deficiency impairs glucose metabolism in Drosophila.

Epoxide hydrolases (EHs) play pivotal roles in detoxification, catabolism, and signaling by converting epoxides into diols and have been implicated in several diseases, such as cancers and diabetes. EH homologs in insects are designated as Juvenile hormone epoxide hydrolases (JHEHs) due to their catalytic activity toward Juvenile hormone (JH). However, the biological function of JHEHs has been controversial in the fruit fly Drosophila melanogaster.

The pericellular function of Fibulin-7 in the adhesion of oligodendrocyte lineage cells to neuronal axons during CNS myelination.

Myelin is an electrical insulator that enables saltatory nerve conduction and is essential for proper functioning of the central nervous system (CNS). It is formed by oligodendrocytes (OLs) in the CNS, and during OL development various molecules, including extracellular matrix (ECM) proteins, regulate OL differentiation and myelination; however, the role of ECM proteins in these processes is not well understood. Our present work is centered on the analyses of the expression and function of fibulin-7 (Fbln7), an ECM protein of the fibulin family, in OL differentiation.

Effect of fezolinetant on patient-reported quality-of-life outcomes: Data from a phase 3b study (DAYLIGHT) of the treatment of moderate to severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy.

Objective: To report patient-reported quality-of-life (QOL) outcomes in the DAYLIGHT study.

Study Design: DAYLIGHT was a phase 3b, randomized, double-blind, 24-week, placebo-controlled study. Participants were women aged ≥40 to ≤65 years with moderate to severe vasomotor symptoms (VMS) considered unsuitable for hormone therapy (HT) (contraindications, caution, stoppers, or averse) randomized 1:1 to placebo or fezolinetant 45 mg once daily.

A combination treatment with a water extract from Euglena gracilis and anti-PD-1 antibody strongly inhibits growth of lung cancer in mice through stimulating tumor-infiltrating lymphocytes.

Here, we investigated the relationship between the attenuation of lung cancer growth due to oral administration of Euglena gracilis water extract (EWE) and T cell stimulation. Orally administered EWE was revealed to increase PD-1 and PD-L1 mRNA and proteins primarily in tumor-infiltrating lymphocytes (TILs), which was correlated with a significant decrease in the tumor weights in mice. A combination treatment with EWE and anti-PD-1 antibody significantly decreased the growth of murine lung tumors more than treatment with either alone by increasing the number of TILs and attenuating T cell exhaustion.

Healthcare burden of narcolepsy in Japan: A retrospective analysis of health insurance claims from the Japan Medical Data Center.

Background: Narcolepsy is a chronic disorder that requires lifelong management; however, few studies have evaluated disease burden of narcolepsy. We estimated the healthcare burden of narcolepsy in Japan using data from the Japan Medical Data Center health insurance claims database.

Methods: This was a retrospective analysis of clinical burden, healthcare resource utilization, and costs among incident narcolepsy cases and matched controls identified between January 1, 2014 and December 31, 2019.

Multi-Scale Pyramid Squeeze Attention Similarity Optimization Classification Neural Network for ERP Detection.

Event-related potentials (ERPs) can reveal brain activity elicited by external stimuli. Innovative methods to decode ERPs could enhance the accuracy of brain-computer interface (BCI) technology and promote the understanding of cognitive processes. This paper proposes a novel Multi-Scale Pyramid Squeeze Attention Similarity Optimization Classification Neural Network (MS-PSA-SOC) for ERP Detection.

Morphology and functionality in biomimetic cultured meat produced from various cellular origins.

Alternative meat production technologies offer the potential to alleviate many of the ethical, environmental, and public health concerns associated with conventional meat production. Cultured meat produced using cell culture technology promises to become a viable alternative to animal-raised meat for the future of the food industry. The process of cultured meat production relies on cell sources harvested from livestock such as bovine, swine, and chicken.

Firm ownerships matter in measuring carbon footprints and its driving forces in China's domestic value chains.

Some research has studied the carbon footprints of the multinational enterprises (MNEs) in the global value chains (GVCs). However, currently there are few studies have studied the carbon footprints of the foreign invested firms (FIFs) distributed in different provinces in China's domestic value chains (DVCs). This paper has used China's inter-provincial input-output table distinguishing domestically owned enterprises (DEs), Hong Kong, Macao, and Taiwan (HMTs) invested enterprises and other foreign invested enterprises (FIEs) to study the carbon footprints of the FIFs in China's DVCs and further analyzed the driving factors of the carbon footprints change.

Grids designed for tomography: Stereovision transmission electron microscopy makes it easy to determine the winding handedness of helical nanocoils.

Determining the handedness of helical nanocoils using transmission electron microscopy (TEM) has traditionally been challenging due to the deep depth of field and transmission nature of TEM, complementary techniques are considered necessary and have been practiced such as low angle rotary shadowing, scanning electron microscopy (SEM), or atomic force microscopy (AFM). These methods require customized sample preparation, making direct comparison difficult. Inspired by the need to identify the helical winding direction from TEM images alone, we developed a specialized tomography grid to capture stereo-pair images, enabling stereopsis.

Modeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics.

Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay.

In vitro activity of omadacycline against geographically diverse rapidly growing nontuberculous mycobacteria (NTM) clinical isolates.

Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens with limited treatment options due to resistance to multiple antibiotic classes. This study aimed to evaluate the in vitro activity of omadacycline and comparator antibiotics against rapidly growing mycobacteria (RGM) clinical isolates. Minimum inhibitory concentration (MIC) evaluation of RGM clinical isolates was performed by two independent laboratories (EU and Japan).

Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic.

Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients.

Impacts of donor age and HLA mismatch on HCT outcomes differ according to the donor CMV serostatus in unrelated allo-HCT.

In unrelated allogeneic hematopoietic cell transplantation (allo-HCT), older and/or HLA-mismatched donors are known risk factors for survival outcomes. In healthy individuals, cytomegalovirus (CMV) seropositivity is associated with impaired adaptive immune systems. We assessed whether the adverse effects of donor risk factors are influenced by the donor CMV serostatus.

Antiseizure Medications in Poststroke Seizures: A Systematic Review and Network Meta-Analysis.

Background And Objectives: The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS.

Methods: We systematically searched electronic databases for studies on patients with PSS on ASMs.

Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Influence of Axial Rotation Between the Femoral Neck and Ankle Joint on Kinematics in Normal Knees: A Cross-Sectional Study.

Background: The effect of axial rotation between the femoral neck and ankle joint (total rotation [TR]) on normal knees is unknown. Therefore, this study aimed to investigate the TR effect on normal knee kinematics.

Methods: Volunteers were divided into groups large (L), intermediate (I), and small (S), using hierarchical cluster analysis based on TR in the standing position.

The mosquito evolves two types of prophenoloxidases with diversified functions.

Insect phenoloxidase, presented as an inactive precursor prophenoloxidase (PPO) in hemolymph, catalyzes melanin formation, which is involved in wound healing, pathogen killing, reversible oxygen collection during insect respiration, and cuticle and eggshell formation. Mosquitoes possess 9 to 16 PPO members across different genera, a number that is more than that found in other dipteran insects. However, the reasons for the redundancy of these PPOs and whether they have distinct biochemical properties and physiological functions remain unclear.

Ankle muscle strength and activation are associated with walking patterns in preschool and school-age children.

Walking patterns can differ between children and adults, both kinematically and kinetically. However, the detailed nature of the ankle pattern has not been clarified. We investigated musculature, biomechanics, and muscle activation strategies and their relevance to walking performance in preschool (PS) and school children (SC), with adults (AD) as reference.

Maternal Gut Inflammation Aggravates Acute Liver Failure Through Facilitating Ferroptosis via Altering Gut Microbial Metabolism in Offspring.

Microbial transmission from mother to infant is important for offspring microbiome formation and health. However, it is unclear whether maternal gut inflammation (MGI) during lactation influences mother-to-infant microbial transmission and offspring microbiota and disease susceptibility. In this study, it is found that MGI during lactation altered the gut microbiota of suckling pups by shaping the maternal microbiota in the gut and mammary glands.

The Association Between COVID-19 Vaccination Uptake and Information-Seeking Behaviors Using the Internet: Nationwide Cross-Sectional Study.

Background: The COVID-19 pandemic, declared in March 2020, profoundly affected global health, societal, and economic frameworks. Vaccination became a crucial tactic in combating the virus. Simultaneously, the pandemic likely underscored the internet's role as a vital resource for seeking health information.

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.

Clinical utility of tumor-infiltrating lymphocyte evaluation by two different methods in breast cancer patients treated with neoadjuvant chemotherapy.

Purpose: The aim of this study was to examine the clinical utility of tumor-infiltrating lymphocytes (TILs) evaluated by "average" and "hot-spot" methods in breast cancer patients.

Methods: We examined 367 breast cancer patients without neoadjuvant chemotherapy (NAC) by average and hot-spot methods to determine the consistency of TIL scores between biopsy and surgical specimens. TIL scores before NAC were also compared with the pathological complete response (pCR) rate and clinical outcomes in 144 breast cancer patients that received NAC.

Tetraspanins CD63 and CD81 as potential prognostic biomarkers in breast cancer.

Exosome markers, CD63 and CD81, belong to the tetraspanin family and are expressed in solid tumors. It has been reported that these tetraspanin family members are prognostic factors in some cancers. However, the expression of CD63 and CD81 in pathological breast cancer specimens has not been reported.

Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity.

To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.