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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.

Superconducting (SC) tokamak JT-60SA plays an essential role in fusion research and development by supporting and complementing the ITER project, providing directions to the DEMO design activity and fostering next generation scientists and engineers. Since the short circuit incident at the terminal joints of equilibrium field coil #1 during the integrated commissioning (IC) in March 2021, both EU and JA implementing agencies (IAs) have examined how to ensure safe operation of JT-60SA by mitigating the risk of possible discharge occurrence inside the cryostat. Based on the experience of the global Paschen tests, the IAs have established a strategy of risk mitigation measures, which is a combination of (i) reinforcement of insulation, (ii) avoiding unnecessary voltage application to the coil systems and (iii) immediate de-energization of the coils when deteriorated vacuum conditions are detected. Thanks to the considerable efforts of the Integrated Project Team members, the IC restarted in May 2023. After confirmation of the SC state of the coil systems (TF, EF and CS), the coil energization test and the plasma operation phase 1 (OP-1) started. The first plasma was successfully achieved on 23 October 2023 with a limited value of voltage and current applied to the coils. The plasma configuration control was also confirmed with low plasma current and low auxiliary heating power conditions. Based on the IO–F4E–QST collaboration, activities of JT-60SA have been shared with the IO and provided an important lesson for ITER assembly and commissioning, and will provide an outstanding contribution to fusion research at large. After OP-1, maintenance & enhancement phase 1 (M/E-1) starts from January 2024, in which in-vessel components are installed, and heating and diagnostic systems are extensively upgraded to allow a high power heating experiment planned in OP-2. In order to make the best use of JT-60SA, a newly organized JT-60SA experiment team will refine the research plan for the future high heating power operation phase.

Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted from the bladder epithelia of rats treated with AAs, including acetoacet-o-toluidine (AAOT) and o-toluidine (OTD), and adductome analysis was performed. Principal component analysis–discriminant analysis revealed that OTD and AAOT observed in urinary bladder hyperplasia could be clearly separated from the controls and other AAs. After confirming the intensity of each adduct, four adducts were screened as having characteristics of the OTD/AAOT treatment. Comparing with the in-house DNA adduct database, three of four candidates were identified as oxidative DNA adducts, including 8-OH-dG, based on mass fragmentation together with high-resolution accurate mass (HRAM) spectrometry data. Therefore, findings suggested that oxidative stress may be involved in the toxicity of rat bladder epithelium exposed to AAs. Consequently, the administration of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, in six-week-old rats fed with 0.6% OTD in their diet resulted in simple hyperplastic lesions in the bladder that were suppressed by apocynin. The labeling indices of Ki67, γ-H2AX, and 8-OHdG were significantly decreased in an apocynin concentration-dependent manner. These findings indicate that oxidative stress may have contributed to the development of urinary cancer induced by OTD.

Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic strains that are primarily transmitted through the consumption of undercooked pork or game meat. They also cause asymptomatic infections, acute hepatitis, acute-on-chronic liver failure, chronic hepatitis, and extrahepatic manifestations. Here, we report a man in his 80s who had chronic hepatitis B, took entecavir for it, and presented with higher levels of alanine aminotransferase (ALT) and jaundice. An abdominal computed tomography scan revealed choledocholithiasis with cholecystolithiasis. Although endoscopic papillary balloon dilatation was performed for the removal of a common bile duct stone, the abnormal liver function tests, including jaundice, were prolonged. After other viral hepatitis and other causes of the liver injury were ruled out, as his serum was positive for immunoglobulin A anti-HEV and HEV genotype 3b RNA, we diagnosed him as having acute hepatitis E. In this case, with chronic hepatitis B and a common bile duct stone, the prolonged abnormal results for the liver function tests seemed to be caused by HEV infection. In conclusion, in cases with high ALT levels after removing choledocholithiasis, other factors, including HEV infection, should be considered to determine the cause of abnormal liver function test results. The further examination of hepatitis D virus infection and high ALT levels may be needed in HBV-infected individuals.

Abstract To provide quantitative feedback on surgical progress to ophthalmologists practicing inner limiting membrane (ILM) peeling, we developed an artificial eye module comprising a quartz crystal resonator (QCR) force sensor and a strain body that serves as a uniform force transmitter beneath a retinal model. Although a sufficiently large initial force must be loaded onto the QCR force sensor assembly to achieve stable contact with the strain body, the highly sensitive and wide dynamic-range property of this sensor enables the eye module to detect the slight forceps contact force. A parallel-plate strain body is used to achieve a uniform force sensitivity over the 4-mm-diameter ILM peeling region. Combining these two components allowed for a measurable force range of 0.22 mN to 29.6 N with a sensitivity error within −11.3 to 4.2% over the ILM peeling area. Using this eye module, we measured the applied force during a simulation involving artificial ILM peeling by an untrained individual and compensated for the long-term drift of the obtained force data using a newly developed algorithm. The compensated force data clearly captured the characteristics of several types of motion sequences observed from video recordings of the eye bottom using an ophthalmological microscope. As a result, we succeeded in extracting feature values that can be potentially related to trainee skill level, such as the mean and standard deviation of the pushing and peeling forces, corresponding, in the case of an untrained operator, to 122.6 ± 95.2 and 20.4 ± 13.2 mN, respectively.

Abstract This paper describes results and analysis of experiment of compression behavior parallel to grain of glulam (Norway Spruce, Japanese cedar, and Japanese cypress), especially in damage zones near loading plates and joints. To investigate the influence factors of physical properties and the mechanism of the damage zone near the loading plates or the joints, compression tests on 90 specimens and surface-measurement tests on 48 specimens were performed. As a result, it was observed that damage zones existed near the loading plates and the joints. The lengths of the damage zone of wood–wood joints are larger than that of wood–steel joints. The length of the damage zone was independent of the load and the height of the specimens. However, the length of the damage zone and its scatter increase as the width of the cross-section increases, as does the roughness on the contact surface. It was considered that the cause of the damage zone is the roughness on the contact surface and the length of the damage zone depends on the roughness on the contact surface. Therefore, the length of the damage zone depends on the processing accuracy on the contact surface and has an increasing trend as the contact-surface area increases. There was the size effect of the height of the specimens on the compressive strength because of knots.

Abstract There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = − 0.42, p 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3–20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti‐HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post‐transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection. [ABSTRACT FROM AUTHOR]

Background and Objectives: Muscle cramps are often observed in patients with liver diseases, especially advanced liver fibrosis. The exact prevalence of muscle cramps in outpatients with liver diseases in Japan is unknown. Patients and Methods: This study examined the prevalence of, and therapies for, muscle cramps in outpatients with liver diseases in Tokyo, Japan. A total of 238 outpatients with liver diseases were retrospectively examined. We investigated whether they had muscle cramps using a visual analog scale (VAS) (from 0, none, to 10, strongest), and also investigated their therapies. Results: Muscle cramps were observed in 34 outpatients with liver diseases (14.3%); their mean VAS score was 5.53. A multivariate analysis demonstrated that older age (equal to or older than 66 years) was the only significant factor as-sociated with muscle cramps. The prevalence of muscle cramps among patients with liver diseases seemed not to be higher. The problem was that only 11 (32.4%) of 34 outpatients received therapy for their muscle cramps. Conclusions: Only age is related to muscle cramps, which is rather weak, and it is possible that this common symptom may not be limited to liver disease patients.

Facial skin aging is the most visible manifestation of aging in the body. In this study, we aimed to rejuvenate aging skin via a one-time intradermal injection of autologous adipose-derived stem cells (ADSCs). Eight patients were enrolled for study. Photographs of patients taken immediately before and 1, 3, 6, and 12 months after ADSC injections were comparatively evaluated for visible skin manifestations. ADSCs were cultured from the abdominal-skin-derived subcutaneous fat tissue, and 1 × 108 cultured ADSCs were injected intradermally into the facial skin. Cultured myoblasts were incubated with the supernatant derived from ADSCs, and the effect was evaluated via glucose consumption and lactic acid production in the medium. Eight cases showed the shallowing and disappearance of wrinkles, including those of the glabella, lower eyelids, crow`s feet, and forehead and nasolabial grooves, a month to several months after treatment. Double eyelids became prominent, and facial pores significantly reduced in size. These effects lasted for over one year. Myoblasts cultured in the presence of an ADSC-derived exosome were activated compared to that of ADSCs cultured without supernatant. The result supports the role of muscle in ADSC skin rejuvenation. The present study first reports that a single intradermal administration of cultured ADSCs rejuvenates aged facial skin over the course of one year. Further, patients exhibited definite double eyelids and pore shrinkage, strongly indicating the active involvement of muscle, which was supported by an in vitro study. Our study also suggested the important role of biological factors delivered from injected stem cells, although the detailed mechanism of rejuvenation effects of ADSC skin injection remains to be clarified.

Abstract This paper describes results and analysis of experimental testing of entire and partial compression strength and stiffness parallel to the grain of solid timber (Japanese cedar). To investigate the spreading effects, the size effect of strength and stiffness, and the mechanism of the damage zone located close to the loading plates, tests on 90 specimens were performed. As a result, it was observed that damage zones existed near the loading plates. The observed spreading effects in the compression parallel to the grain were very small which justifies neglecting them regarding strength and stiffness. Although a presence of a size effect of the compression strength parallel to the grain of glulam specimens with knots was reported, the compression strength parallel to the grain of solid wood specimens without knots does not have a size effect. The height and width of the cross-section of the specimens have an influence on the damage zones and, hence, on the effective modulus of elasticity of the full height of the specimens. The compression strength has a correlation with the density of the timber and the width of the annual rings.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. Methods: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. Results: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. Conclusions: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.