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Background: Basal cell hyperplasia is commonly observed in nasal polyp epithelium of eosinophilic chronic rhinosinusitis (eCRS). We examined the function and mechanisms of basal cell hyperplasia in the pathophysiology of eCRS. Methods: We found that normal human bronchial epithelial (NHBE) cells obtained basal cell characteristics when cultured with PneumaCult™-Ex Plus Medium. Most of the cells passaged three times expressed basal cell surface markers CD49f and CD271 by flow cytometry, and basal cell nuclear marker p63 by immunohistochemical staining. We named these NHBE cells with basal cell characteristics cultured Basal-like cells (cBC), and NHBE cells cultured with BEGM™ cultured Epithelial cells (cEC). The characteristics of cBC and cEC were examined and compared by RNA sequencing, RT-PCR, ELISA, and cell proliferation studies. Results: RNA sequencing revealed that cBC showed higher gene expression of thymic stromal lymphopoietin (TSLP), IL-8, TLR3, and TLR4, and lower expression of PAR-2 compared with cEC. The mRNA expression of TSLP, IL-8, TLR3, and TLR4 was significantly increased in cBC, and that of PAR-2 was significantly increased in cEC by RT-PCR. Poly(I:C)-induced TSLP production and LPS-induced IL-8 production were significantly increased in cBC. IL-4 and IL-13 stimulated the proliferation of cBC. Finally, the frequency of p63-positive basal cells was increased in nasal polyp epithelium of eCRS, and Ki67-positive proliferating cells were increased in p63-positive basal cells. Conclusions: Type 2 cytokines IL-4 and IL-13 induce basal cell hyperplasia, and basal cells exacerbate type 2 inflammation by producing TSLP in nasal polyp of eCRS.

Abstract Background Work-family enrichment refers to the extent to which experiences in one role improve the quality of life in another role, and the bidirectionality indicates that benefits derived from work can be applied to family and vice versa. Parent nurses, that is, female nurses who are raising preschool children, play a major role at work and in the family. Thus, work-family enrichment is significant for them. The Work-Family Enrichment Scale cannot be generalized to parent nurses. This study was aimed at developing and psychometrically validating a draft Work-Family Enrichment Scale for Parent Nurses. Methods A questionnaire survey was conducted among 1,090 parent nurses who were randomly sampled from hospitals with more than 200 beds in Japan. The survey evaluated (1) a draft Work-Family Enrichment Scale for Parent Nurses, (2) the Japanese version of the Work-Family Enrichment Scale, and (3) the Positive Spillover Scale. The scales were psychometrically evaluated for internal consistency, construct validity, and criterion-related validity. Results Data from 503 participants (age, mean ± standard deviation [range] 35.5 ± 4.96 [23–47] years) were analyzed. Results of exploratory factor analysis, the work to family enrichment direction yielded five factors for 23 items: “emotional fulfillment,” “efficiency,” “ability to lead,” “displaying industriousness,” and “self-growth.” Cronbach’s alpha coefficients ranged from 0.862 to 0.914. In the family-to-work enrichment direction, there were five factors for 28 items: “help-seeking,” “receptiveness,” “expansion of one’s horizon,” “efficiency,” and “emotional fulfillment.” Cronbach’s alpha coefficients ranged from 0.790 to 0.907. Additionally, the correlation coefficients reporting criterion-related validity were 0.685 and 0.619 with regard to the Japanese version of the Work-Family Enrichment Scale and 0.596 and 0.534 with the Positive Spillover Scale for the Work-to-Family Enrichment Scale and the Family-to-Work Enrichment Scale for Parent Nurses, respectively. Conclusions The Work-Family Enrichment Scale for Parent Nurses has adequate reliability and validity and can be used as an effective measure to assess the positive aspects of work and family roles among female parent nurses.

Abstract Lung adenocarcinoma (LUAD) is the most important subtype of lung cancer. It is well known that the gut microbiome plays an important role in the pathophysiology of various diseases, including cancer, but little research has been done on the intestinal microbiome associated with LUAD. Utilizing bioinformatics tools and data analysis, we identified novel potential prognostic biomarkers for LUAD. To integrate differentially expressed genes and clinical significance modules, we used a weighted correlation network analysis system. According to the Peryton database and the gutMGene database, the composition and structure of gut microbiota in LUAD patients differed from those in healthy individuals. LUAD was associated with 150 gut microbiota and 767 gut microbiota targets, with Krüppel-like factor 5 (KLF5) being the most closely related. KLF5 was associated with immune status and correlated well with the prognosis of LUAD patients. The identification of KLF5 as a potential prognostic biomarker suggests its utility in improving risk stratification and guiding personalized treatment strategies for LUAD patients. Altogether, KLF5 could be a potential prognostic biomarker in LUAD. Graphical Abstract

Abstract Although immune checkpoint inhibitors (ICIs) are effective in some patients with salivary gland carcinoma (SGC), biomarkers which predict the efficacy and prognosis of SGC patients treated with pembrolizumab have not been identified. We conducted a multi-institutional retrospective cohort study to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with recurrent and/or metastatic SGC and to determine optimal cut-off values of the combined positive score (CPS) and tumor proportion score (TPS) as numerical expression levels of programmed death-ligand 1 (PD-L1), which predict the efficacy of pembrolizumab. Furthermore, we investigated the association of patient characteristics and hematological markers with clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). From 2016 to 2021, 27 patients were included in the analysis. ORR of SGC was 25.9%. Optimal cut-off values of CPS and TPS were 15 and 25%, respectively. ORRs of CPS-high and TPS-high were 55.6 and 75.0%, respectively, and significantly higher than those of CPS-low and TPS-low. Furthermore, patients with a low platelet-lymphocyte ratio (PLR) had a significantly longer PFS. No grade 4 or greater adverse events were observed. This study demonstrated the efficacy and safety of pembrolizumab monotherapy and identified optimal cut-off values of CPS and TPS.

Abstract Background The objective of this study is to assess whether urethral preservation can be performed safely using frozen section analysis (FSA) of the urethral stump on urethral recurrence after radical cystectomy. Methods Between June 2012 and July 2022, we investigated consecutive male patients who underwent urethral FSA during radical cystectomy for urothelial carcinoma. For FSA‐abnormal cases, urethrectomy was performed, and for FSA‐normal cases, the urethra was preserved. The diagnostic accuracy of FSA was assessed in comparison with the pathological findings of the permanent sections of the same tissue. Postoperatively, computed tomography and urinary cytology were performed as routine surveillance of recurrence. Results Of the 77 patients included in this study, three patients with abnormal FSA underwent concurrent urethrectomy. The negative predictive value of urethral FSA was 100%. With a median postoperative follow‐up of 38 months (interquartile ranges 21–71), no urethral recurrence was observed. Conclusions FSA may be useful in determining the indication for urethrectomy.

Objectives: Pelvic organ prolapse (POP) is a significant health-care problem for older women. We have treated POP surgically using laparoscopic sacrocolpopexy (LSC) or robotic-assisted sacrocolpopexy (RSC). The original LSC and RSC procedures were done with anterior and posterior meshes; however, the use of the single mesh procedure is increasing because of its simplicity and safety. There have been few reports about the change in quality of life (QOL) using the single mesh procedure. Therefore, the present study aimed to retrospectively evaluate the change in QOL by LSC and RSC using a single anterior mesh for women without posterior compartment prolapse. Materials and Methods: We performed LSC or RSC using a single anterior mesh in 52 patients who had POP without posterior vaginal wall prolapse between August 2018 and October 2022. We assessed the QOL before and after surgery using prolapse-QOL (P-QOL) questionnaires. Results: All patients who received LSC or RSC with a single anterior mesh left the hospital as scheduled without severe perioperative complications. There were no instances of wound infection or vaginal mesh extrusion. The recovery rate of questionnaires was 63.5% (33/52). All QOL score domains improved significantly, and there were no questionnaire parameters that worsened. Conclusion: LSC or RSC using only a single anterior mesh improves P-QOL with a low incidence of surgical complications for POP patients who did not have posterior vaginal wall prolapse. LSC or RSC with a single anterior mesh may be a prospective new procedure for POP.

Abstract Large Language Models (LLMs), such as the General Pre-trained Transformer (GPT), have shown remarkable performance in various cognitive tasks. However, it remains unclear whether these models have the ability to accurately infer human perceptual representations. Previous research has addressed this question by quantifying correlations between similarity response patterns of humans and LLMs. Correlation provides a measure of similarity, but it relies pre-defined item labels and does not distinguish category- and item- level similarity, falling short of characterizing detailed structural correspondence between humans and LLMs. To assess their structural equivalence in more detail, we propose the use of an unsupervised alignment method based on Gromov–Wasserstein optimal transport (GWOT). GWOT allows for the comparison of similarity structures without relying on pre-defined label correspondences and can reveal fine-grained structural similarities and differences that may not be detected by simple correlation analysis. Using a large dataset of similarity judgments of 93 colors, we compared the color similarity structures of humans (color-neurotypical and color-atypical participants) and two GPT models (GPT-3.5 and GPT-4). Our results show that the similarity structure of color-neurotypical participants can be remarkably well aligned with that of GPT-4 and, to a lesser extent, to that of GPT-3.5. These results contribute to the methodological advancements of comparing LLMs with human perception, and highlight the potential of unsupervised alignment methods to reveal detailed structural correspondences.

In swash plate type axial piston pumps, slipper/swash plate sliding surfaces is subject to high fluctuating load. Therefore, the slippers are required to provide stable operation and reduce losses due to sliding. The behavior of the slipper fluctuates in a complex manner due to changes in the hydraulic pressure in the cylinder and inertial forces caused by the reciprocating motion of the piston. However, the time variation of the oil film thickness distribution of the slipper has not been measured. Furthermore, there are no measurements of the movement of the spherical joint connecting the slipper and piston, which affects the slipper behavior. In this study, the visualized sliding test rig with a sapphire glass swash plate was developed. The oil film thickness distribution of the slipper and the rotation of the slipper and the piston were measured continuously during one rotation of the pump.

Abstract Acute immune responses with excess production of cytokines, lipid/chemical mediators, or coagulation factors, often result in lethal damage. In addition, the innate immune system utilizes multiple types of receptors that recognize neurotransmitters as well as pathogen-associated molecular patterns, making immune responses complex and clinically unpredictable. We here report an innate immune and adrenergic link inducing lethal levels of platelet-activating factor. Injecting mice with toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS), cell wall N-glycans of Candida albicans, and the α2-adrenergic receptor (α2-AR) agonist medetomidine induces lethal damage. Knocking out the C-type lectin Dectin-2 prevents the lethal damage. In spleen, large amounts of platelet-activating factor (PAF) are detected, and knocking out lysophospholipid acyltransferase 9 (LPLAT9/LPCAT2), which encodes an enzyme that converts inactive lyso-PAF to active PAF, protects mice from the lethal damage. These results reveal a linkage/crosstalk between the nervous and the immune system, possibly inducing lethal levels of PAF.

Abstract Background Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported. Case presentation A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications. Conclusion The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.

Abstract The association of type 2 diabetes with certain cancer risk has been of great interest for years. However, the effect of diabetic medications on cancer development is not fully understood. Prospective clinical trials have not elucidated the long‐term influence of hypoglycemic drugs on cancer incidence and the safety for cancer‐bearing patients with diabetes, whereas numerous preclinical studies have shown that antidiabetic drugs could have an impact on carcinogenesis processes beyond the glycemic control effect. Because there is no evidence of the safety profile of antidiabetic agents on cancer biology, careful consideration would be required when prescribing any medicines to patients with diabetes and existing tumor. In this review, we discuss the potential influence of each diabetes therapy in cancer ‘initiation’, ‘promotion’ and ‘progression’.

Abstract Objectives The aim of present study was to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBOT) as a primary therapy combined with standard systemic corticosteroid treatment for sudden sensorineural hearing loss (SSNHL) compared to treatment without the use of HBOT (non‐HBOT) through clinical data and advanced analytical approaches. Study Design Case–control study. Methods Conducted across three Japanese medical centers involving 298 SSNHL patients diagnosed between 2020 and 2023. Inclusion criteria encompassed first onset and treatment, WHO grade 3 or 4 initial hearing impairment, receipt of systemic corticosteroid therapy within 14 days of symptom onset, and initiation of HBOT within the same timeframe for the case group. The primary outcome measure was the difference in hearing improvement (mean hearing level in decibels, dB) between the two groups, assessed by pure‐tone audiometry at baseline and 3 months post‐treatment, using the inverse probability of treatment weighting (IPTW) method adjusted for covariate differences. Results The study included 67 patients in the HBOT group and 68 in the non‐HBOT group. The HBOT group exhibited significantly greater hearing improvement (IPTW‐adjusted difference: 7.6 dB, 95% CI 0.4–14.7; p = 0.038). Patients without vertigo in the HBOT group demonstrated substantial hearing improvement (11.5 dB, 95% CI 2.3–20.6; p = 0.014), whereas those with vertigo showed no significant improvement (−1.8 dB, 95% CI −11.8–8.3; p = 0.729). The HBOT group also had a significantly higher association with complete recovery (IPTW‐adjusted odds ratio: 2.57, 95% CI 1.13–5.85; p = 0.025). Conclusion In SSHNL, HBOT combination therapy yielded slightly but significantly improved hearing outcomes compared to non‐HBOT treatment. Level of Evidence 4.

The side chain dynamics of poly(quinoxaline-2,3-diyl)s (PQXs) are expected to influence their conformation. To investigate these dynamics experimentally, quasielastic neutron scattering (QENS) was performed for PQXs in deuterated tetrahydrofuran (THF-d8) and deuterated 1,1,2-trichloroethane/THF (1,1,2-TCE-d3/THF-d8), in which they formed right-handed and left-handed helical structures, respectively. The mean-square displacement of the PQX side chains in 1,1,2-TCE-d3/THF-d8 was lower than that in THF-d8. Furthermore, QENS complementary studies and molecular dynamics simulations unraveled a coupling between the main-chain and side chain dynamics of PQXs, suggesting the possibility of controlling the main-chain helical chirality through the dynamics of chiral side chains. These insights present a novel strategy for the design of synthetic helical macromolecules with precise chirality control. [ABSTRACT FROM AUTHOR]

Abstract Mutualism profoundly affects the morphology and ecological evolution of both hosts and symbionts involved. Heterocyathus is a solitary scleractinian coral that lives on soft substrata, and sipunculan worms live symbiotically in the tube-like cavities (orifice) inside the coral skeletons. This habitat provides protection to the sipunculan worms against predators and—owing to the mobility of the worms—prevents the coral from being buried with sediments. The orifice growth is closely related to the symbiont sipunculan worms; however, this has not been previously elucidated. Here, we clarified the growth process of scleractinian coral orifices and the influence of sipunculan activity on this. The orifices were originally formed by rapid accretion deposits. The coral soft tissue enveloping the growth edge of the orifice repeatedly retreated to the outer side due to direct damage to the soft part and/or excessive stress caused by the rubbing of the sipunculan through locomotion, excretion, and feeding behaviour. This resulted in a toppled-domino microskeletal structure appearance and maintenance of the orifice growth. These outcomes demonstrate the first example of the direct influence of symbionts on the skeletal morphogenesis of scleractinian corals. The mutualism between the two organisms is maintained by the beneficial confrontation in forming orifices.

Abstract This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien–Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54–8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23–8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78–34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83–7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14–16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis.

Abstract Due to the synchronous circulation of seasonal influenza viruses and severe acute respiratory coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19), there is need for routine vaccination for both COVID-19 and influenza to reduce disease severity. Here, we prepared individual WPVs composed of formalin-inactivated SARS-CoV-2 WK 521 (Ancestral strain; Co WPV) or influenza virus [A/California/07/2009 (X-179A) (H1N1) pdm; Flu WPV] to produce a two-in-one Co/Flu WPV. Serum analysis from vaccinated mice revealed that a single dose of Co/Flu WPV induced antigen-specific neutralizing antibodies against both viruses, similar to those induced by either type of WPV alone. Following infection with either virus, mice vaccinated with Co/Flu WPV showed no weight loss, reduced pneumonia and viral titers in the lung, and lower gene expression of proinflammatory cytokines, as observed with individual WPV-vaccinated. Furthermore, a pentavalent vaccine (Co/qFlu WPV) comprising of Co WPV and quadrivalent influenza vaccine (qFlu WPV) was immunogenic and protected animals from severe COVID-19. These results suggest that a single dose of the two-in-one WPV provides efficient protection against SARS-CoV-2 and influenza virus infections with no evidence of vaccine interference in mice. We propose that concomitant vaccination with the two-in-one WPV can be useful for controlling both diseases.

It is unknown whether plasma concentrations of a matricellular protein periostin change in association with the development of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In 113 patients with aneurysmal SAH of World Federation of Neurological Surgeons grades 1–3 at admission, plasma periostin concentrations were serially measured at days 1–3, 4–6, 7–9 and 10–12 after SAH onset. Measured periostin levels and clinical variables were compared between patients with and without angiographic vasospasm. Periostin concentrations were significantly higher in patients with angiographic vasospasm at days 4–6 and 7–9. Receiver operating characteristic curve analyses indicated that cutoff plasma periostin values of 54.3 ng/ml at days 4–6 and 58.1 ng/ml at days 7–9 predicted or diagnosed angiographic vasospasm development with a specificity of 66.0 % and a sensitivity of 72.7 %, and a specificity of 75.0 % and a sensitivity of 55.0 %, respectively. Multivariate analyses also revealed that increased plasma periostin concentrations at days 7–9 was independently associated with angiographic vasospasm development. This study showed for the first time that plasma periostin levels were increased in patients with angiographic vasospasm. These findings suggest that plasma periostin can serve as a biomarker and may be a new therapeutic target for angiographic vasospasm after SAH.