Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing.

In vivo genome editing holds great therapeutic potential for treating monogenic diseases by enabling precise gene correction or addition. However, improving the efficiency of delivery systems remains a key challenge. In this study, we investigated the use of lipid nanoparticles (LNPs) for in vivo knock-in of ectopic DNA.

Long-term follow-up study of Kudo Type-5 elbow prosthesis in patients with rheumatoid arthritis: minimum 10-year clinical outcomes.

Objectives: Rheumatoid arthritis often leads to debilitating damage in the elbow joint, which may require total elbow arthroplasty (TEA). The Kudo TEA is one of the unlinked type prostheses with reportedly favorable outcomes. However, there is limited information available regarding its long-term performance.

The health-economic impact of urine albumin-to-creatinine ratio testing for chronic kidney disease in Japanese patients with type 2 diabetes.

Aims/introduction: This analysis seeks to evaluate the cost-effectiveness of urine albumin-to-creatinine ratio testing compared with urine protein-creatinine ratio testing and no urine testing for the identification of kidney damage in individuals with type 2 diabetes who have, or are at risk of, chronic kidney disease in Japan.

Materials And Methods: A health-economic model estimated the clinical and economic consequences of different tests to evaluate kidney damage in line with Japanese guidelines, taking a Japanese healthcare perspective. Differences in the diagnostic performance of tests were considered by the integration of real-world Japanese data.

A Food Intake Estimation System Using an Artificial Intelligence-Based Model for Estimating Leftover Hospital Liquid Food in Clinical Environments: Development and Validation Study.

Background: Medical staff often conduct assessments, such as food intake and nutrient sufficiency ratios, to accurately evaluate patients' food consumption. However, visual estimations to measure food intake are difficult to perform with numerous patients. Hence, the clinical environment requires a simple and accurate method to measure dietary intake.

How do question-answer exchanges among generations matter for children's happiness?

Intergenerational exchange plays an increasing role in realizing sustainable societies. Question-answer exchanges are the trigger for individuals to initiate some intergenerational relations, and the literature has established that inquisitiveness (curiosity about something and someone different) contributes to people's generativity and happiness. However, little is known about how children's inquisitiveness influences their generative concern and happiness.

Histopathological Confirmation of Axonal Sprouting in Regenerative Peripheral Nerve Interface.

Symptomatic neuroma represents a debilitating complication after major limb amputation. The regenerative peripheral nerve interface (RPNI) has emerged as a reproducible and practical surgery aimed at mitigating the formation of painful neuroma. Although previous animal studies revealed axonal sprouting, elongation, and synaptogenesis of proximal nerve stump within the muscle graft in RPNI, there is a lack of reports confirming these physiological reactions at the histopathological level in human samples.

Evolution of genetic architecture and gene regulation in biphenyl/PCB-degrading bacteria.

A variety of bacteria in the environment can utilize xenobiotic compounds as a source of carbon and energy. The bacterial strains degrading xenobiotics are suitable models to investigate the adaptation and evolutionary processes of bacteria because they appear to have emerged relatively soon after the release of these compounds into the natural environment. Analyses of bacterial genome sequences indicate that horizontal gene transfer (HGT) is the most important contributor to the bacterial evolution of genetic architecture.

A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses α-tocopherol component.

Background: Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models.

A bacterial sulfoglycosidase highlights mucin O-glycan breakdown in the gut ecosystem.

Mucinolytic bacteria modulate host-microbiota symbiosis and dysbiosis through their ability to degrade mucin O-glycans. However, how and to what extent bacterial enzymes are involved in the breakdown process remains poorly understood. Here we focus on a glycoside hydrolase family 20 sulfoglycosidase (BbhII) from Bifidobacterium bifidum, which releases N-acetylglucosamine-6-sulfate from sulfated mucins.

Diversity and Evolution of Integrative and Conjugative Elements Involved in Bacterial Aromatic Compound Degradation and Their Utility in Environmental Remediation.

Integrative and conjugative elements (ICEs) are mobile DNA molecules that can be transferred through excision, conjugation, and integration into chromosomes. They contribute to the horizontal transfer of genomic islands across bacterial species. ICEs carrying genes encoding aromatic compound degradation pathways are of interest because of their contribution to environmental remediation.

Extension contracture stiff knee in haemophilia: Surgical timing and procedure for total knee arthroplasty.

Introduction: Total knee arthroplasty (TKA) for a stiff knee of patients with haemophilia (PWH) represents a challenge for orthopaedic surgeons for the difficulties of exposing the knee and high complication rate compared to a flexible knee.

Aim: To optimize the surgical exposure in primary TKA for PWH and to propose a threshold angle of extension contracture in treating haemophilic knee joints, retrospectively.

Methods: Sixty-seven primary TKAs for PWH (mean age, 48 years) were performed, and incisional approaches to joint were standard (58 cases) and V-Y quadricepsplasty (V-Y) (9 cases).

Priority effects shape the structure of infant-type Bifidobacterium communities on human milk oligosaccharides.

Bifidobacteria are among the first colonizers of the infant gut, and human milk oligosaccharides (HMOs) in breastmilk are instrumental for the formation of a bifidobacteria-rich microbiota. However, little is known about the assembly of bifidobacterial communities. Here, by applying assembly theory to a community of four representative infant-gut associated Bifidobacterium species that employ varied strategies for HMO consumption, we show that arrival order and sugar consumption phenotypes significantly affected community formation.

Comprehensive Analysis of Lipid Composition in Human Foremilk and Hindmilk.

Precision nutrition, also referred to as personalized nutrition, focuses on the individual to determine the individual's most effective eating plan to prevent or treat disease. A precision nutrition for infants requires the determination of the profile of human milk. We compared the lipid profiles of the foremilk (i.

Accuracy of an Artificial Intelligence-Based Model for Estimating Leftover Liquid Food in Hospitals: Validation Study.

Background: An accurate evaluation of the nutritional status of malnourished hospitalized patients at a higher risk of complications, such as frailty or disability, is crucial. Visual methods of estimating food intake are popular for evaluating the nutritional status in clinical environments. However, from the perspective of accurate measurement, such methods are unreliable.

Transcription Factor Hematopoietically Expressed Homeobox Protein (Hhex) Negatively Regulates Osteoclast Differentiation by Controlling Cyclin-Dependent Kinase Inhibitors.

We investigated the role of hematopoietically expressed homeobox protein (Hhex) in osteoclast development. Trimethylation of lysine 27 of histone H3 at the -regulatory element of was maintained and that of lysine 4 was reduced during receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis, which was associated with a reduction of expression. Overexpression of in bone marrow-derived macrophages inhibited, whereas suppression promoted, RANKL-induced osteoclastogenesis in vitro.

How does inquisitiveness matter for generativity and happiness?

Inquisitiveness (curiosity & acceptance to something and someone different) is the main engine for one person to initiate some relation, and the literature has established that maintaining nice relationships with friends, family and general others contributes to generativity and happiness. However, little is known about how generativity and happiness are characterized by inquisitiveness. We hypothesize that inquisitiveness is a fundamental determinant for generativity and happiness, empirically examining the relationships along with cognitive, noncognitive and sociodemographic factors.

Changes in intracellular activation-related gene expression and induction of Akt contribute to acquired resistance toward nelarabine in CCRF-CEM cell line.

Drug resistance is a major problem in treatment with nelarabine, and its resolution requires elucidation of the underlying mechanisms. We established two nelarabine-resistant subclones of the human T-cell lymphoblastic leukemia cell line CCRF-CEM. The resistant subclones showed changes in the expression of several genes related to nelarabine intracellular activation and inhibition of apoptosis.

A New ICE Subfamily Integrative and Conjugative Element Responsible for Horizontal Transfer of Biphenyl and Salicylic Acid Catabolic Pathway in the PCB-Degrading Strain KF716.

Integrative and conjugative elements (ICEs) are chromosomally integrated self-transmissible mobile genetic elements. Although some ICEs are known to carry genes for the degradation of aromatic compounds, information on their genetic features is limited. We identified a new member of the ICE family carrying biphenyl catabolic genes and salicylic acid catabolic genes from the PCB-degrading strain KF716.

Diversification of a Fucosyllactose Transporter within the Genus .

Human milk oligosaccharides (HMOs), which are natural bifidogenic prebiotics, were recently commercialized to fortify formula milk. However, HMO assimilation phenotypes of bifidobacteria vary by species and strain, which has not been fully linked to strain genotype. We have recently shown that specialized uptake systems, particularly for the internalization of major HMOs (fucosyllactose [FL]), are associated with the formation of a -rich gut microbial community.

Outcomes of Scarf and Akin Osteotomy with Intra-Articular Stepwise Lateral Soft Tissue Release for Correcting Hallux Valgus Deformity in Rheumatoid Arthritis.

Background: The effectiveness of scarf and Akin osteotomy with intra-articular lateral soft tissue release for the correction of hallux valgus (HV) in patients with rheumatoid arthritis (RA) has not been elucidated.

Methods: A total of 36 feet in 28 patients with RA who had scarf and Akin osteotomy with intra-articular stepwise lateral soft tissue release between 2015 and 2020 at a single institute were investigated retrospectively, with a mean follow-up period of 32.0 ± 16.

Clinical Outcomes After First Metatarsophalangeal Joint Arthrodesis by Flat Cut Joint Preparation With Individual Adjustment for Sagittal Alignment.

Sagittal misalignment is a major cause of patient dissatisfaction and re-operation after first metatarsophalangeal (MTP) joint arthrodesis. The stereotypical application of the fixed angle would be undesirable, especially in cases of flat or cavus foot. We retrospectively reviewed 31 cases (27 patients) in which first MTP joint arthrodesis was performed using the flat cut joint preparation technique with reference to the plantar clearance beneath the pulp of the toe while simulating weightbearing by pushing a board against the sole.

An Electrical Stimulation Culture System for Daily Maintenance-Free Muscle Tissue Production.

Low-labor production of tissue-engineered muscles (TEMs) is one of the key technologies to realize the practical use of muscle-actuated devices. This study developed and then demonstrated the daily maintenance-free culture system equipped with both electrical stimulation and medium replacement functions. To avoid ethical issues, immortal myoblast cells C2C12 were used.