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Abstract We derive the new identity in homotopy algebras which directly corresponds to the Schwinger-Dyson equations in quantum field theory. As an application, we derive the Ward-Takahashi identities. We demonstrate that the Ward-Takahashi identities are reproduced in several examples. In general, our formula contains divergence. We mediate this problem by introducing stubs known in the context of string field theory. With the regularization, we can calculate the anomaly such as axial U(1) anomaly in vector-like U(1) gauge theory.

Abstract Background To prevent the progression of diabetic nephropathy, educational programs to improve self-management are important. However, the effectiveness of educational programs to prevent worsening of diabetic kidney disease on renal function and quality of life is under characterised. Objectives The purpose of this study was to conduct a systematic review and meta-analysis to identify effective educational programs for diabetic kidney disease and the impact of educational programs on improving renal function and quality of life in patients with diabetic kidney disease. Design The study design is a systematic review and meta-analysis. Method We systematically collected research papers, and two authors independently selected papers and evaluated them according to the inclusion criteria. The extracted data were entered into Review Manager 5.4, and the standardised mean difference of the delta estimated glomerular filtration rate (ml/min/1.73m2/year) was calculated using a random effect size model for the renal function evaluation. Results Overall, 207 articles were retrieved from five electronic databases and three studies were shortlisted. Data from the two studies on delta estimated glomerular filtration rate (ml/min/1.73 m2/year) were combined, but the results were not significant. The effect on quality of life was observed in only one of the three studies, so they could not be pooled. Conclusions Effective educational programs for self-management of diabetic kidney disease could not be identified because of the small number of studies included. Educational programs reviewed also lacked a significant effect on kidney function, likely related to their short durations. The effect of the education programs on quality of life is unknown because studies could not be pooled.

Abstract Purpose Thermoelastic stress analysis (TSA) was used to evaluate stress changes over the entire surface of a specimen. This study aimed to assess the relationship between femoral stress distribution, analysed using TSA and changes in bone mineral density (BMD) after total hip arthroplasty (THA). Methods Stress changes in the simulated bone before and after taper‐wedge stem insertion were measured using the TSA. Stress changes were compared with BMD changes around the stem 1 year after surgery in a THA patient (58 hips) with the same taper‐wedge stem. Subsequently, we compared the correlation between stress changes and BMD changes. Results TSA revealed significant stress changes before and after stem insertion, with prominent alterations in the proximal medial region. The BMD changes at 1 year post‐THA exhibited a 15%–25% decrease in the proximal zones, while Zones 2–6 showed a −6% to 3% change. Notably, a strong positive correlation (0.886) was found between the stress change rate and BMD change rate. Conclusions This study demonstrated a high correlation between femoral stress distribution assessed using TSA and subsequent BMD changes after THA. The TSA method offers the potential to predict stress distribution and BMD alterations postsurgery, aiding in implant development and clinical assessment. Combining TSA with finite element analysis could provide even more detailed insights into stress distribution. Level of Evidence Case series (with or without comparison).

Abstract Limited information regarding the anatomical and visual prognosis of macular telangiectasia (MacTel) type 2 in the Asian population is currently available. Herein, we conducted a retrospective longitudinal analysis of Japanese patients diagnosed with MacTel type 2. Disease progression was evaluated using the Simple MacTel Classification developed by Chew EY et al. in 2023, and its association with visual changes was analyzed. Sixteen eyes of eight Japanese patients were included in the study, with an average follow-up period of 8.2 ± 3.9 years (range, 2.2–14.0). At the initial visit, 7 (44%) and 5 (31%) eyes were classified as Grade 2 (central ellipsoid zone break) and Grade 3 (noncentral pigment), respectively. The proportion of eyes that progressed by 1 or 2-steps in grade after 1, 3, 5, 8, and 12 years was 0%, 14%, 43%, 70%, and 100%, or 0%, 7%, 7%, 30%, and 75%, respectively. The visual acuity significantly deteriorated during the follow-up period, particularly in the two eyes with full-thickness macular holes (FTMH). Three out of 7 patients exhibited low serum serine concentrations, although no apparent correlation with anatomical or visual outcomes was observed. Overall, this cohort demonstrated chronic disease progression, both anatomically and functionally, in eyes with MacTel type 2, with FTMH potentially associated with greater visual loss.

Background and objectives: The initial symptom that triggers granulomatosis with polyangiitis (GPA) diagnosis is rarely ocular. We describe a case with a single ocular lesion identified as probable GPA due to proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positivity according to the diagnostic criteria of the Ministry of Health in Japan; the lesion repeatedly worsened. Materials and methods: A 25-year-old female visited the Department of Ophthalmology, Asahi General Hospital, with upper eyelid swelling and conjunctival and episcleral hyperemia of the left eye. Both hordeolum and eyelid cellulitis were suspected, as the condition was resistant to treatment with antibiotic eye drops. Episcleritis was suspected due to localized hyperemia in the upper part of the eye. Upon treatment with antibacterial agents and steroid eye drops, the swelling and the hyperemia repeatedly worsened every week. Results: Blood samples were positive for PR3-ANCA, and GPA with an isolated ocular lesion was considered. After oral steroid treatment, the patient had no recurrence for 4 years. There was no systemic involvement in the upper respiratory tract, lungs, or kidneys. Conclusions: Diagnosing GPA with ocular symptoms as initial manifestations is challenging. GPA should be considered in treatment-resistant eyelid, orbital, and episcleral lesions, even at a young age.

Pierisin is a DNA-targeting ADP-ribosyltransferase found in cabbage white butterfly (Pieris rapae). Pierisin transfers an ADP-ribosyl moiety to the 2-amino group of the guanine residue in DNA, yielding N2-(ADP-ribos-1-yl)-2′-deoxyguanosine (N2-ADPR-dG). Generally, such chemically modified DNA is recognized as DNA damage and elicits cellular responses, including DNA repair pathways. In Escherichia coli and human cells, it has been experimentally demonstrated that N2-ADPR-dG is a substrate of the nucleotide excision repair system. Although DNA repair machineries can remove most lesions, some unrepaired damages frequently lead to mutagenesis through DNA replication. Replication past the damaged DNA template is called translesion DNA synthesis (TLS). In vitro primer extension experiments have shown that eukaryotic DNA polymerase κ is involved in TLS across N2-ADPR-dG. In many cases, TLS is error-prone and thus a mutagenic process. Indeed, the induction of G:C to T:A and G:C to C:G mutations by N2-ADPR-dG in the hypoxanthine phosphoribosyltransferase gene mutation assay with Chinese hamster cells and supF shuttle vector plasmids assay using human fibroblasts has been reported. This review provides a detailed overview of DNA repair, TLS and mutagenesis of N2-ADPR-dG induced by cabbage butterfly pierisin-1.

The Receptor Activator Nuclear of κB Ligand (RANKL) plays an important function in immune responses, activating osteoclast cells and unchanged bone resorption, which in turn leads to bone erosion and inflammation. Genetic variants in the promoter region of the RANKL gene could lead to a higher risk of rheumatoid arthritis (RA). Objective: To assess the association of rs9533155 (-693C>G) and rs9533156 (-643T>C) genetic variants with RA risk. Methods: A case–control study was carried out. A total of 94 patients with RA (RA group) and 134 subjects without any rheumatologic disease (control group) were included. Genetic DNA was extracted from peripheral white blood cells (leukocytes). Genetic variant rs9533155 (-693C>G) was screened by an approach based on Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), while rs9533156 (-643T>C) was screened using quantitative polymerase chain reaction (qPCR) with TaqMan probes. RANKL serum levels were measured by ELISA. Results: For rs9533155 (-693C>G), the polymorphic homozygous genotype frequencies (CC) were higher in the RA group (p = 0.006). Individuals carrying the risk genotype presented higher levels of serum RANKL. Carriers of the polymorphic homozygous genotype in the dominant model (CC vs. CG + GG) had an increased risk of developing RA (OR: 1.8, 95% CI 1.04 to 3.1). No association between rs9533156 (-643T>C) and the haplotypes with RA risk was observed. Conclusion: The rs9533155 (-693C>G) genetic variant exhibits a potential role in RA risk. The studied population had no association with the rs9533156 (-643T>C) genetic variant.

Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71–93); specificity, 52% (95%CI: 31–72); positive predictive value, 78% (95%CI: 70–84); and negative predictive value, 62% (95%CI: 44–77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.

Pierisin-1 was serendipitously discovered as a strong cytotoxic and apoptosis-inducing protein from pupae of the cabbage butterfly Pieris rapae against cancer cell lines. This 98-kDa protein consists of the N-terminal region (27 kDa) and C-terminal region (71 kDa), and analysis of their biological function revealed that pierisin-1 binds to cell surface glycosphingolipids on the C-terminal side, is taken up into the cell, and is cleaved to N- and C-terminal portions, where the N-terminal portion mono-ADP-ribosylates the guanine base of DNA in the presence of NAD to induce cellular genetic mutation and apoptosis. Unlike other ADP-ribosyltransferases, pieisin-1 was first found to exhibit DNA mono-ADP-ribosylating activity and show anti-cancer activity in vitro and in vivo against various cancer cell lines. Pierisin-1 was most abundantly produced during the transition from the final larval stage to the pupal stage of the cabbage butterfly, and this production was regulated by ecdysteroid hormones. This suggests that pierisn-1 might play a pivotal role in the process of metamorphosis. Moreover, pierisin-1 could contribute as a defense factor against parasitization and microbial infections in the cabbage butterfly. Pierisin-like proteins in butterflies were shown to be present not only among the subtribe Pierina but also among the subtribes Aporiina and Appiadina, and pierisin-2, -3, and -4 were identified in these butterflies. Furthermore, DNA ADP-ribosylating activities were found in six different edible clams. Understanding of the biological nature of pierisin-1 with DNA mono-ADP-ribosylating activity could open up exciting avenues for research and potential therapeutic applications, making it a subject of great interest in the field of molecular biology and biotechnology.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1β, transforming growth factor-beta (TGF-β), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-β superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1—patients with sepsis treated with conventional treatment without vitamin C; Group 2—patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31–0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Abstract The CRISPR-Cas9 method for generation of knock-in mutations in rodent embryos yields many F0 generation candidates that may have the designed mutations. The first task for selection of promising F0 generations is to analyze genomic DNA which likely contains a mixture of designed and unexpected mutations. In our study, while generating Prlhr-Venus knock-in reporter mice, we found that genomic rearrangements near the targeted knock-in allele, tandem multicopies at a target allele locus, and mosaic genotypes for two different knock-in alleles occurred in addition to the designed knock-in mutation in the F0 generation. Conventional PCR and genomic sequencing were not able to detect mosaicism nor discriminate between the designed one-copy knock-in mutant and a multicopy-inserted mutant. However, by using a combination of Southern blotting and the next-generation sequencing-based RAISING method, these mutants were successfully detected in the F0 generation. In the F1 and F2 generations, droplet digital PCR assisted in establishing the strain, although a multicopy was falsely detected as one copy by analysis of the F0 generation. Thus, the combination of these methods allowed us to select promising F0 generations and facilitated establishment of the designed strain. We emphasize that focusing only on positive evidence of knock-in can lead to erroneous selection of undesirable strains.

Abstract Ruptured retinal arterial macroaneurysm (RAM) can cause sub-inner limiting membrane (ILM) hemorrhage, leading to acute vision loss in the elderly. Vitrectomy has been established as an effective treatment to remove hemorrhage and facilitate visual recovery. Although optical coherence tomography (OCT) is useful for the diagnosis of sub-ILM hemorrhage before surgery, little is known about the postoperative OCT findings. Here, we retrospectively investigated the records of nine eyes of nine patients who underwent surgery for sub-ILM hemorrhage due to RAM rupture. On postoperative OCT, hyperreflectivity throughout the full thickness of the central fovea was observed in eight eyes (88.9%), and disruption of the ellipsoid/interdigitation zone (EZ/IZ) was observed in seven out of eight eyes (87.5%). The widths of the hyperreflectivity and EZ disruption gradually decreased. Visual recovery was least favorable in two eyes, in which the EZ line continuation did not recover until the final follow-up. The OCT findings corresponded to the hemorrhagic staining identified on fundus photographs in at least four eyes; as per the fundus photographs the findings persisted even after the hemorrhage was absorbed. In contrast, the OCT findings resembled the appearance before the development of a full-thickness macular hole, suggesting fragility caused by the RAM rupture.

Background: Primary stability of the femoral stem is important for the long-term results of cementless total hip arthroplasty. Cementless collared stems have been known to have higher stability than collarless stems when there is a contact between the collar and the calcar. The purpose of this study was to compare the stabilities of collared stem and collarless stem in 2 loading conditions: 1) flat walking and 2) stair climbing. Methods: We constructed 3 finite element models. In the first model, the collar had contact with the calcar. The second model had a 1 mm gap between the calcar and the collar. The third model was constructed with a collarless stem. The proximal femur around the stem was divided into 3 zones: the upper zone (Gruen zones 1 and 7), the middle zone (Gruen zones 2 and 6), and the lower zone (Gruen zones 3 and 5). The micromotion at the stem/bone interface was measured at each zone of the 3 models under the 2 loading conditions. Results: The results showed that collared stems were more stable when the collar was in contact with the calcar than when a gap was left between the collar and the calcar. In particular, collar contact was highly effective in suppressing the micromotion proximal to the stem. Conclusions: Compared to the collarless stem, the collared stem had comparable stability when there was a gap at the collar and calcar interface and higher stability when there was contact between the collar and the calcar.