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Abstract Fecal microbiota transplantation (FMT) is a therapeutic modality for treating neonatal calf diarrhea. Several practical barriers, including donor selection, fecal collection, and a limited timeframe for FMT, are the main constraints to using fresh feces for implementing on-farm FMT. We report the utility of FMT with pretreated ready-to-use frozen (F) or freeze-dried (FD) microorganisms for treating calf diarrhea. In total, 19 FMT (F-FMT, n = 10 and FD-FMT, n = 9) treatments were conducted. Both FMT treatments were 100% clinically effective; however, multi-omics analysis showed that FD-FMT was superior to F-FMT. Machine learning analysis with SourceTracker confirmed that donor microbiota was retained four times better in the recipient calves treated with FD-FMT than F-FMT. A predictive model based on receiver operating characteristic curve analysis and area under the curve showed that FD-FMT was more discriminative than F-FMT of the observed changes in microbiota and metabolites during disease recovery. These results provide new insights into establishing methods for preparing fecal microorganisms to increase the quality of FMT in animals and may contribute to FMT in humans.

Abstract The serotonergic system modulates the neural circuits involved in jaw movement; however, the role of serotonin (5-HT) neurons in masticatory movement remains unclear. Here, we investigated the effect of selective activation of 5-HT neurons in the dorsal raphe nucleus (DRN), or the raphe obscurus nucleus (ROb), on voluntary masticatory movement using transgenic mice expressing the channelrhodopsin-2 (ChR2) mutant (C128S) in central 5-HT neurons. During voluntary mastication, DRN blue light illumination increased masticatory frequency and decreased the root mean square peak amplitude of electromyography (EMG) in the masseter muscles. DRN blue light illumination also decreased EMG burst duration in the masseter and digastric muscles. These changes were blocked by a 5-HT2A receptor antagonist. Conversely, ROb blue light illumination during voluntary mastication did not affect masticatory frequency and EMG bursts in the masseter and digastric muscles. DRN or ROb blue light illumination during the resting state did not induce rhythmic jaw movement such as mastication but induced an increase in EMG activity in masseter and digastric muscles. These results suggest that both DRN and ROb 5-HT neurons may facilitate jaw movement. Furthermore, DRN 5-HT neuron may contribute to changes in masticatory patterns during the masticatory sequence.

Abstract The management of eosinophilic esophagitis (EoE) has not been completely established yet. There is a controversy over the universal maintenance therapy for EoE to prevent esophageal fibrostenotic complications. Using an employer-based insurance claim database from January 2005 to September 2022, we investigated the treatment patterns of EoE and the occurrence of esophageal complications. The treatment patterns were analyzed at a 6-month interval from the diagnosis of EoE. The time to treatment discontinuation of proton pump inhibitor (PPI)/potassium-competitive acid blocker (P-CAB) was evaluated by the Kaplan–Meier method. Of 15,200,895 individuals, 615 patients with EoE were ultimately analyzed with the median follow-up time from the index date of 700 days. PPI/P-CAB and swallowed topical steroids accounted for 80% and 4.6% of the initial therapy, respectively. PPI/P-CAB use rapidly decreased by 40% in the first 6 months and afterwards reinitiation was rarely seen. The median time to treatment discontinuation were 172 days (95% CI 147–206 days) for PPI/P-CAB. Only 1 EoE patient developed esophageal fibrostenotic complications after the diagnosis. With the low incidence of esophageal complications, the universal maintenance therapy may not be necessary for mild EoE patients often seen in Japan.

Abstract Exophiala dermatitidis (E. dermatitidis), which causes skin or respiratory disease, is occasionally fatal in immunocompromised patients. Here, we report the unique antifungal potency of terbinafine (TRB), which targets squalene epoxidase, against E. dermatitidis (SQLEED) using various in vitro approaches. The versatile antifungal activities, including fungicidal activity, biofilm formation inhibition, biofilm eradication activity, and the combination effect of TRB, posaconazole (PSC), and amphotericin B (AmB) with great antifungal potency against E. dermatitidis were evaluated using crystal violet and cell viability assay. TRB formed an H-bond through Y102 in SQLEED in the binding model. E. dermatitidis hyphae elongated and attached to a cell scaffold, forming a membrane-like biofilm. TRB and PSC showed more potent antibiofilm activities than AmB, and exhibited post-antifungal effects without incubation against E. dermatitidis conidia, reducing growth at lower concentrations. In contrast, AmB exhibited strong dose- and time-dependent killing and biofilm-eradication activities. The combination of TRB and PSC was more effective than that of TRB and AmB or PSC and AmB. Although the tissue migration of TRB must be considered, these data suggest that TRB and PSC may be useful agents and a potent combination in severely immunocompromised patients with refractory and systemic E. dermatitidis infection.

Abstract The Ogasawara Islands, one of the UNESCO World Natural Heritage Site located about 1000 km south of Japan’s main island, harbor numerous endemic species, many of which are as endangered. One of the endemic plant species, Lobelia boninensis, found in the Mukojima, Chichijima, and Hahajima archipelagoes, is endangered due to predation. As part of conservation efforts, translocation is now underway, especially on Chichijima. However, we lack essential information, such as the genetic population structure, to develop appropriate translocation strategies for both wild and planted individuals. Here, we aimed to identify the conservation units and the origin of planted individuals by estimating the genetic population structure and phylogenetic relationships across all habitats of this species. We identified two distinct genetic clusters, indicating genetic differentiation between the northern and southern populations. The genetic population components detected at an isolated site on Chichijima showed a mixture of these distinct clusters, probably due to hybridization. The transplanted individuals in Chichijima were found to have originated from a population in Hahajima. These results suggest the presence of two distinct conservation units. Furthermore, the current translocation strategy poses a risk of genetic contamination between these units, highlighting the need for revised conservation management practices.

Abstract We demonstrated previously that sorting nexin 25 (SNX25) in nerve-associated macrophages plays critical roles in pain sensation by regulating tissue NGF content under both physiological and neuropathic conditions. In the present study, we apply the SNX25–NGF paradigm to tactile perception by showing that Snx25 +/- mice or macrophage-specific Snx25 conditional knock-out (mcKO) mice had weaker responses to tactile stimuli in normal conditions. Snx25 mcKO mice responded poorly to transcutaneous electrical stimuli at a frequency of 5 Hz (C fiber responses), but normally to stimuli at a frequency of 250 Hz (Aδ fiber responses) or of 2000 Hz (Aβ fiber responses). CX3CR1-positive dermal macrophages were frequently found near calcitonin gene–related peptide (CGRP)- positive nerves and, less frequently, tyrosine hydroxylase (TH)-positive nerves. We confirmed that the tissue content of NGF was lower in Snx25 mcKO mice than in wild-type mice, and in turn, dermal NGF injection restored tactile sensitivity in Snx25 +/- mice and Snx25 mcKO mice to normal levels. These results indicate that CGRP-positive C-nociceptors (possibly also TH-positive C-LTMRs) associated dermal macrophages control tactile perception by producing NGF and secreting it into the dermis.

Abstract We observe both s-series and p-series excitons by using sum frequency generation spectroscopy on monolayer (1L-)MX2 (M = Mo, W, X = S, Se) encapsulated by hexagonal boron nitride (hBN). Moreover, we perform numerical calculations with the Rytova-Keldysh potential and obtain the relative dielectric constant of hBN among other parameters. The obtained relative dielectric constant can be approximated by the high-frequency limit of the infrared dispersion even though the exciton binding energies are almost on the phonon resonances in hBN. This suggests that the theoretically indicated modification of the exciton level structure due to the phonon resonances is negligible. The power-law scaling of exciton binding energies indicates that dielectric screening of 1L-MX2 exciton levels other than 1s can be approximated by that of a 3D hydrogen model with the dielectric constant of hBN.

Abstract The nursing practice environment is essential for improving the quality of nursing practice and patient service. Performing secondary analysis of data from the work environment for hospital nurses in Japan (WENS-J) study, this research investigated whether an improved, healthier work environment could enhance nurses’ psychological empowerment. Self-administered questionnaire responses of 2,438 participants from 23 participating general hospitals with over 200 beds in municipalities with a population of 200,000 or more were analyzed. The questionnaire recorded participating nurses’ demographic characteristics and utilized two scales: the Practice Environment Scale of the Nursing Work Index (PES-NWI) and the Psychological Empowerment Instrument (PEI), which identified adequate work environments and measured the internalization of organizational goals and objectives, respectively. Most participants (93.7%) were female nurses with a mean age of 33.7 years. Multilevel analysis (hierarchical linear models) revealed that the total PEI score was significantly related to the PES-NWI composite score and all subscales after adjusting for nurses’ demographic characteristics, such as age (coefficient 0.33–0.72, all p

Abstract Evaluating complicated stress across the elbow under joint motion remains difficult. Here, we aimed to evaluate the distribution of the subchondral bone density in the normal elbow bones and further characterize their spatial relationships during elbow motion to estimate the loading stress across the articular surface using three-dimensional computed tomography bone models. The normal elbow joint exhibited a consistent distribution pattern of subchondral bone density. High-density regions were distributed in the capitellum and posterior humeral trochlea, sagittal ridge of the ulnar trochlear notch and ulnar-volar side of the radial head. Motion analyses revealed that the high-density regions proximate with elbow flexion with forearm pronation in the radiocapitellar joint and in the fully extended position in the ulnohumeral joint. This reasonably reflects the stress acting on the joint surface under actual loading conditions. These findings suggest that daily activities involving lifting or carrying objects in these positions are stress-prone activities.

Abstract Multispectral long-wave infrared (LWIR) ranging is a technique that estimates the distance to the object based on wavelength-dependent absorption of LWIR light through the air. Prior works require time-consuming measurements for calibration and solve non-linear inverse problems, which sometimes falls into a local minimum. In this paper, we propose a linear representation that connects the measurements and the scene parameters using the affine matrix. In this representation, the distance and the temperature of the object can be obtained as a closed-form solution and the calibration cost can be reduced to at least three observations. In real-world experiments, we demonstrate that our method is effective to reduce the calibration cost while keeping the precision of the depth estimation.

Herein, we describe a novel posterior lumbar interbody fusion (PLIF) technique with annulus fibrosus (AF) release and the use of expandable cages (called “anterior-release PLIF” [ARPLIF]). In this technique, posterior column osteotomy (PCO) and AF release provide excellent intervertebral mobility. AF release involves circumferentially peeling off the AF above or below the endplate between the fixed vertebrae under radiographic guidance without cutting the AF and anterior longitudinal ligament. Subsequently, high-angle variable-angle expandable cages are used to simultaneously expand both sides before inserting the percutaneous pedicle screws and correcting to achieve good local lumbar lordosis. PCO and AF release achieve excellent intervertebral mobility. Intervertebral mobility and simultaneous expansion of both cages disperse the force on the endplates, reducing cage subsidence, and the high-angle cages facilitate high intervertebral angle creation. The novel ARPLIF intervertebral manipulation technique can promote good local lumbar lordosis formation.

Abstract The transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for plasma aldosterone concentration (PAC) assays has raised concerns over its impact on primary aldosteronism (PA) diagnosis. This study investigated the correlation between PAC and renin values using RIA, CLEIA, and liquid chromatography/mass spectrometry/mass spectrometry (LC–MS/MS), established cutoff values for PA diagnosis using the aldosterone-to-renin ratio (ARR) with PAC_CLEIA, and assessed the differences in PAC values by measuring weak mineralocorticoids (WMs). This retrospective study evaluated 312 serum PAC samples using RIA, CLEIA, and LC–MS/MS, and analyzed 315 plasma renin samples. Method correlations were assessed through Passing-Bablok regression. Receiver operating characteristic curves determined ARR cutoffs for PA diagnosis. WMs were quantified to evaluate their impact on ΔPAC (RIA-LC–MS/MS) through multiple regression analysis. PAC_CLEIA and PAC_LC-MS/MS values were highly correlated. ARRs derived from PAC_RIAs demonstrated more false positives and lower specificity than ARRs using PAC_CLEIA or PAC_LC-MS/MS. WMs significantly influenced ΔPAC in both the PA and non-PA groups. ARRs using PAC_CLEIA are valuable for determining PA cutoffs in clinical practice. The transition to PAC using CLEIA may enhance PA detection rates. WMs were found to interfere with PAC measurements in the RIA method, affecting outcomes.

Abstract There have been several reports of skin manifestations in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected on the skin surface, including the sebum, of these patients. In this study, SARS-CoV-2 RNA was detected using real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of skin surface lipids (SSLs) collected using an oil-blotting film from the faces of hospitalized patients with COVID-19. Human transcriptome analysis was also performed using the same samples. In facial SSLs of patients with COVID-19, the RT-PCR positivity rate was 84.6% (11/13 samples) within 5 days and 30.4% (7/23 samples) by 6–10 days of symptom onset. In the transcriptome analysis, the most characteristic SSL-RNA profile was the upregulation of interferon-stimulated gene (ISG)-related genes, such as ISG15, IFITM1, and MX1. This study presents an alternative technique using SSLs for non-invasive SARS-CoV-2 RNA detection and simultaneous analysis of human molecular pathogenesis in patients with COVID-19.

Abstract Thallium bromide (TlBr) semiconductor detectors are being developed as promising candidates for high-detection-efficiency, high-energy-resolution, and room-temperature gamma-ray spectrometers. This study presents methods for evaluating TlBr crystal quality and carrier transport characteristics using neutron Bragg-dip imaging and the time-of-flight method for pulsed-laser-induced carriers, respectively. Neutron Bragg-dip imaging effectively determines the crystal orientation distribution, revealing crystal imperfections and grain boundaries. Time-of-flight measurements provide a spatial distribution of carrier mobility. In this study, two samples obtained from both the upstream and downstream region in the crystal ingot were evaluated. Although both samples show similar crystal quality, the upstream sample showed high carrier mobility across all areas, whereas the downstream sample exhibits low mobility in some areas. These findings suggest that, at least within the range of carrier mobility currently obtained, the effect of crystal integrity on carrier mobility is less significant than that of impurities. In conclusion, combining neutron Bragg-dip imaging with carrier mobility measurements offers a comprehensive approach to evaluating and improving TlBr detectors.

Abstract This study aimed to develop an extraction-free method for quantitative and qualitative detection of HBV DNA compared to traditional nucleic acid extraction. Paired serum and dried blood spot (DBS) samples from 67 HBsAg-positive and 67 HBsAg-negative individuals were included. Two samples with known HBV DNA titers (~ 109 copies/mL) were examined by extraction-free detection using three surfactants (0.2 to 1% of Sodium dodecyl sulfate:SDS, N-Lauroylsarcosine sodium salt:NL, Sodium dodecyl benzene sulfonate:SDBS), two stabilizing agents (0.1 or 0.01% 2-Mercaptoethanol:2ME and 3.5 or 7% Bovine Serum Albumin:BSA) and two Taq polymerases (Fast Advanced and Prime Direct Probe). HBV DNA in all 67 HBsAg-positive and 67 HBsAg-negative serum and DBS samples was directly quantified by Rt-PCR using 0.4% SDS or 0.4% NL with Fast Advance or Prime Direct Probe Taq. Extraction-free amplification was also performed. Detection limits were varied by different surfactants and Taq. SDS combined with Fast Advanced Taq showed lower detection limits, while SDS with Prime Direct Probe Taq outperformed NL or SDBS-based detection. Adding 2ME to SDS improved detection limit with Prime Direct Probe Taq but not significantly compared to SDS alone. BSA did not significantly enhance detection limits but provided insights into sample stability. The senitivity and specificity of 0.4% SDS and NL in combination with either Fast advanced or Prime Direct Probe Taq polymerase in serum samples were > 90% and 100% resepctively, while it was > 80% and 100% respectively in DBS samples. Extraction-free HBV DNA amplification provided 100% identity with original genomes. Our study suggests that SDS, NL or SDBS-based extraction-free HBV DNA detection strategies using Prime Direct Probe Taq have potential to simplify and accelerate HBV DNA detection with high sensitivity and specificity in both serum and DBS samples, with implications for resource-limited settings and clinical applications. Utilizing surfactants with 2ME is optional, and further research and validation are necessary to broaden its application in real-world diagnostics.

Abstract Background The production of inflammatory cytokines is reportedly increased in patients with coronavirus disease 2019 (COVID-19), causing the migration of neutrophils and monocytes to lung tissues. This disrupts the air–blood barrier by damaging the bronchial epithelial and vascular endothelial cells. As multiorgan dysfunction in sepsis is considered to be partly caused by complement activation, which can cause lung injury in patients with COVID-19. There are limited studies examining the link between complement activation in patients with COVID-19. This study aimed to AQinvestigate the association of complement activation with the pathophysiology of COVID-19. Twenty-seven patients with COVID-19 were enrolled in this study and classified into two groups depending on the indication for mechanical ventilation. Plasma complement factors (C3a, C5a, Ba, and sC5b-9), complement regulators (sCD59 and factor H), interleukin-6 (IL-6), and syndecan-1 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Results: All complement factors and regulators, IL-6, and syndecan-1 levels were significantly elevated in patients with COVID-19 compared with those in healthy controls. C5a and sC5b-9 levels were decreased significantly in the invasive mechanical ventilation (IMV) group compared with those in the non-IMV group. Syndecan-1 levels were significantly increased in the IMV group compared with those in the non-IMV group. Conclusions: Complement activation is an exacerbating factor for lung injury in patients with COVID-19. Complement factors are nonessential predictors of mechanical ventilation; however, syndecan-1 could be a biomarker of COVID-19 severity in patients.

Abstract Thrombospondin 2 (TSP2) plays a vital role in collagen/fibrin formation, bone growth, vascular density regulation, hemostasis, and cell adhesion. Close associations of serum TSP2 with histological severity in non-alcoholic fatty liver disease and chronic hepatitis C were reported. The present study investigated the significance of circulating TSP2 in chronic hepatitis B patients. Eighty-seven biopsy-proven chronic hepatitis B patients were analyzed in cross-sectional Study 1 to search for correlations between serum TSP2 levels prior to liver biopsy and clinicopathological parameters. In longitudinal Study 2, 51 chronic hepatitis B patients with long-term follow-up (mean: 7.5 years) were examined for changes in serum TSP2 levels during nucleos(t)ide analog (NA) therapy along with trends in hepatocarciongenesis. In Study 1, serum TSP2 levels were not significantly associated with portal inflammation or fibrosis. Study 2 revealed that serum TSP2 was significantly decreased after 48 weeks of NA therapy (P

Abstract A tendon’s ordered extracellular matrix (ECM) is essential for transmitting force but is also highly prone to injury. How tendon cells embedded within and surrounding this dense ECM orchestrate healing is not well understood. Here, we identify a specialized quiescent Scx +/Axin2 + population in mouse and human tendons that initiates healing and is a major functional contributor to repair. Axin2 + cells express stem cell markers, expand in vitro, and have multilineage differentiation potential. Following tendon injury, Axin2 + -descendants infiltrate the injury site, proliferate, and differentiate into tenocytes. Transplantation assays of Axin2-labeled cells into injured tendons reveal their dual capacity to significantly proliferate and differentiate yet retain their Axin2 + identity. Specific loss of Wnt secretion in Axin2 + or Scx + cells disrupts their ability to respond to injury, severely compromising healing. Our work highlights an unusual paradigm, wherein specialized Axin2 + /Scx + cells rely on self-regulation to maintain their identity as key organizers of tissue healing.

Abstract Amyotrophic lateral sclerosis (ALS) progressively impairs motor neurons, leading to muscle weakness and loss of voluntary muscle control. This study compared the effects of SOD1 mutation on masticatory and limb muscles from disease onset to death in ALS model mice. Notably, limb muscles begin to atrophy soon after ALS-like phenotype appear, whereas masticatory muscles maintain their volume and function in later stages. Our analysis showed that, unlike limb muscles, masticatory muscles retain their normal structure and cell makeup throughout most of the disease course. We found an increase in the number of muscle satellite cells (SCs), which are essential for muscle repair, in masticatory muscles. In addition, we observed no reduction in the number of muscle nuclei and no muscle fibre-type switching in masticatory muscles. This indicates that masticatory muscles have a higher resistance to ALS-related damage than limb muscles, likely because of differences in cell composition and repair mechanisms. Understanding why masticatory muscles are less affected by ALS could lead to the development of new treatments. This study highlights the importance of studying different muscle groups in ALS to clarify disease aetiology and mechanisms.

Abstract Iron is an essential mineral that supports numerous biological functions. Studies have reported associations between iron dysregulation and certain cardiovascular and neurodegenerative diseases, but the direction of influence is not clear. Our goal was to use computational approaches to better understand the role of genetically predicted iron levels on disease risk. We meta-analyzed genome-wide association study summary statistics for serum iron levels from two cohorts and two previous meta-analyses. We then obtained summary statistics from 11 neurodegenerative, cerebrovascular, cardiovascular or lipid traits to assess global and regional genetic correlation between iron levels and these traits. We used two-sample Mendelian randomization (MR) to estimate causal effects. Sex-stratified analyses were also carried out to identify effects potentially differing by sex. Overall, we identified three significant global correlations between iron levels and (i) coronary heart disease, (ii) triglycerides, and (iii) high-density lipoprotein (HDL) cholesterol levels. A total of 194 genomic regions had significant (after correction for multiple testing) local correlations between iron levels and the 11 tested traits. MR analysis revealed two potential causal relationships, between genetically predicted iron levels and (i) total cholesterol or (ii) non-HDL cholesterol. Sex-stratified analyses suggested a potential protective effect of iron levels on Parkinson’s disease risk in females, but not in males. Our results will contribute to a better understanding of the genetic basis underlying iron in cardiovascular and neurological health in aging, and to the eventual identification of new preventive interventions or therapeutic avenues for diseases which affect women and men worldwide.

Abstract Background Biological age, especially epigenetic age derived from the epigenetic clock, is a significant measure of aging, considering the differences in aging rates among individuals. The epigenetic clock, a machine learning-based algorithm, uses DNA methylation states to estimate biological age. Previous studies have reported inconsistent associations between physical activity (PA) and the epigenetic clock, especially second-generation clocks such as PhenoAge and GrimAge. This study aimed to clarify this relationship using cross-sectional data from Japanese participants aged 40–69. Methods We used two datasets from the Saga J-MICC study, of which 867 samples were available for analysis. DNA methylation data from peripheral blood samples were used to calculate the epigenetic age using the epigenetic clocks PhenoAge and GrimAge. PA and sedentary time were measured using a single-axis accelerometer, while self-reported PA, sedentary time, and covariates were assessed using a self-administered questionnaire. The association between PA or sedentary time and epigenetic age acceleration was assessed using multiple linear regression. Results Pearson's correlation coefficients between accelerometer-based and self-reported PA variables ranged from 0.09 to 0.20. Multivariable regression analysis showed that accelerometer-based PA and sedentary time were associated with epigenetic age decelerations and accelerations, respectively. However, self-reported PA was not associated with the epigenetic age accelerations. Conclusions These results indicate that reducing sedentary time and increasing PA were associated with slowing both PhenoAge and GrimAge, even in East Asian populations with different exercise habits, body shapes, and lifestyles. This study highlights the potential of objective second-generation epigenetic age acceleration as an outcome index for healthcare interventions and clinical applications.

Abstract Drought is the primary driver of wildfires in humid regions, and the main drought drivers for wildfire occurrence and spread vary across different humid climatic areas. This study explores the suitability of different drought descriptions for wildfires under various humid temperate climates in Japan. Based on wildfire data from 1995 to 2012, statistical and correlation analyses were conducted to examine the performance of effective humidity (EH) and soil moisture (SM) as indicators of atmospheric and soil drought. EH is used for nationwide wildfire and drought warnings in Japan. The results show that EH is significantly influenced by seasonal and regional factors, with its ability to assess drought for wildfire varying accordingly, whereas SM demonstrates a more consistent ability to assess drought across different seasons and regions. Correlation analysis revealed that atmospheric drought better explains the drought conditions for wildfire ignition in 11 prefectures, mainly concentrated in the northern regions along the Sea of Japan. In contrast, the correlation coefficients for SM were higher in 33 prefectures, particularly along the Pacific coast, indicating that soil drought better explains the drought conditions for burned areas in these prefectures.

Abstract Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as ‘improved’, ‘stable’, and ‘deteriorated’. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials.

Abstract The antigen-mediated B cell isolation method, based on the detection of surface IgG (sIgG), has increased the efficiency of therapeutic antibody (Ab) discovery. However, the reduction in sIgG expression on B cells during plasma cell differentiation presents challenges as it enables Ab production from only a small subset of B cells (e.g., memory B cells). The present study aimed to addressed this problem by developing a workflow to isolate human-IgG-secreting hybridoma cells produced by cell fusion, the majority of which express sIgG. We showed that our sIgG-based antigen-coated bead separation method efficiently enriched hybridoma cells expressing antigen-specific Abs with a yield of 83.5% (from the cell fusion pool) and a positive rate of 73.2%. Furthermore, because the separation could be performed after only a short (1–2-day) culture period following cell fusion, diverse hybridoma clones could be obtained, minimizing clonal selection and the incidence of duplicates. Given that the expression of membrane-bound IgG and sIgG are regulated by different splicing mechanisms, we speculate that the cell fusion step potentially attenuated the suppression of human sIgG expression. Overall, our proposed method is expected to markedly improve the efficiency of therapeutic Ab candidate production, which will have important clinical implications.

Abstract Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of KRAS mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (P

Abstract Conventional pyrolysis methods to chemically recycle plastic waste require significant energy input owing to inefficient energy transfer from the heat sources to plastics and the generation of excess CO2. Accordingly, there is an urgent need to develop alternative methods for the chemical recycling of waste plastics to limit global warming. In this study, the use of microwaves (MWs) as an efficient energy source for pyrolysis and chemical recycling. However, because plastic is transparent to MW energy, a method that utilizes carbon materials as MW-absorbing heating elements (MWAHEs) was developed. This method directly converted high-density polyethylene (HDPE) into light chemicals in up to 94% yield with 45% ethylene selectivity. A two-stage pyrolysis system incorporating MWAHE-assisted MW pyrolysis was also developed to produce light chemicals in 95% yield with 49% ethylene selectivity. From a chemical engineering perspective, this two-step pyrolysis system is an efficient and feasible method for producing valuable light olefins. This study also demonstrates that MWAHE assisted MW pyrolysis is effective for the chemical recycling of plastic waste. This study offers potential solutions for the environmental problems posed by plastic waste by developing efficient and scalable methods for its chemical recycling.

Abstract Tick-borne bacteria of the genera Rickettsia and Coxiella cause several emerging veterinary and human infectious diseases. Ticks of the genus Hyalomma are medically important vectors due to their potential role in the transmission of pathogens to vertebrate hosts. There is an inadequate knowledge on tick-borne Rickettsia spp. and Coxiella spp. in ticks infesting transhumant camels in Pakistan. In this study, we conducted a molecular survey for screening of Rickettsia spp. and Coxiella spp. in ticks infesting camels. Seven hard tick species including Hyalomma dromedarii, Hyalomma anatolicum, Hyalomma scupense, Hyalomma isaaci, Hyalomma turanicum, Hyalomma asiaticum, and Rhipicephalus sanguineus s.l were confirmed on camels in three distinct physiographic regions of Khyber Pakhtunkhwa, Pakistan. A subset of morphologically identified ticks were subjected to molecular assays for the genetic characterization of ticks and the detection and genetic characterization of Rickettsia and Coxiella species using standard genetic markers. Ticks screened for pathogens resulted in the detection of Rickettsia aeschlimannii and Candidatus Rickettsia shennongii and Coxiella burnetii. The molecular analysis further reveals the presences of an undetermined Rickettsia aeschlimannii-like species, that is making a distinct phylogenetic clade with R. aeschlimannii. The detection of pathogens in camel ticks poses potential health hazards as these ticks frequently bites humans. Molecular screening of Rickettsia spp. and Coxiella spp. associated with camel ticks is a preliminary step toward the surveillance of evaluating their zoonotic threats in the region.

Abstract The influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p

Abstract Age-related macular degeneration (AMD) is associated with the dysfunction and degeneration of retinal pigment epithelium (RPE) cells. Here, we examined how the formation and expansions of cell clusters are regulated by the differentiation of the RPE cells. In this study, ARPE-19 cells were cultivated in standard or differentiation media, i.e., without or with nicotinamide, to evaluate the spreading of cell clusters specified with differentiated cell phenotypes. Mitochondria membrane potential (MMP) and the distribution of the RPE cell clusters was also monitored with or without rotenone, a mitochondrial electron transport chain (ETC) complex I inhibitor. Cultured ARPE-19 cells generated scattered cell clusters composed mostly of smaller size cells expressing the differentiation markers mouse anti-cellular retinaldehyde–binding protein (CRALBP) and Bestrophin only in differentiation medium. After the increase of the number of clusters, the clusters appeared to paracellularly merge, resulting in expansion of the area occupied by the clusters. Of note, the cells within the clusters selectively had high MMP and were in accordance with the expression of RPE differentiation markers. Rotenone repressed the formation of the clusters and decreased intracellular MMP. The above results suggest that clustering of RPE cells with functional mitochondria plays a pivotal role in RPE cell differentiation process and the ETC complex I inhibition greatly influences the composition of RPE cells that are degenerated or differentiation disposed.

Abstract Third-party punishment (TPP) is an altruistic behavior or sense willing to punish transgressors as a third party not directly involved in the transgression. TPP is observed worldwide, regardless of tradition and culture, and is essential for morality in human society. Moreover, even preverbal infants display TPP-like judgement, suggesting that TPP is evolutionarily conserved and innate. Thus, it is possible that non-human animals display TPP-like behavior, although TPP has been said to be human-specific. We investigated whether or not male mature Wistar rats displayed TPP-like behaviors when they witnessed deadly aggression by an unknown aggressive mouse toward another unknown victim mouse. Normally reared rats did not display TPP-like behaviors, but rats reared with extensive affectionate handling by human caretakers as beloved pets contacted the unknown aggressive mice in a gentle manner leading to reduced aggression toward the unknown victim mice, even when the aggressive mice fought back. Furthermore, the handled rats touched unknown rat pups that were drowning in water and anesthesia-induced comatose rats more frequently than control rats. These findings suggest a possibility that TPP is not in fact human-specific and innate but rather an acquired behavior that flourishes in affectionate circumstances.

Abstract Heme serves as a prosthetic group in hemoproteins, including subunits of the mammalian mitochondrial electron transfer chain. The first enzyme in vertebrate heme biosynthesis, 5-aminolevulinic acid synthase 1 (ALAS1), is ubiquitously expressed and essential for producing 5-aminolevulinic acid (ALA). We previously showed that Alas1 heterozygous mice at 20–35 weeks (aged-A1 +/−s) manifested impaired glucose metabolism, mitochondrial malformation in skeletal muscle, and reduced exercise tolerance, potentially linked to autophagy dysfunction. In this study, we investigated autophagy in A1 +/−s and a sarcopenic phenotype in A1 +/−s at 75–95 weeks (senile-A1 +/−s). Senile-A1 +/−s exhibited significantly reduced body and gastrocnemius muscle weight, and muscle strength, indicating an accelerated sarcopenic phenotype. Decreases in total LC3 and LC3-II protein and Map1lc3a mRNA levels were observed in aged-A1 +/−s under fasting conditions and in Alas1 knockdown myocyte-differentiated C2C12 cells (A1KD-C2C12s) cultured in high- or low-glucose medium. ALA treatment largely reversed these declines. Reduced AMP-activated protein kinase (AMPK) signaling was associated with decreased autophagy in aged-A1 +/−s and A1KD-C2C12s. AMPK modulation using AICAR (activator) and dorsomorphin (inhibitor) affected LC3 protein levels in an AMPK-dependent manner. Our findings suggest that heme deficiency contributes to accelerated sarcopenia-like defects and reduced autophagy in skeletal muscle, primarily due to decreased AMPK signaling.

Abstract Tumor-associated macrophages (TAMs) originating from monocytes are crucial for cancer progression; however, the mechanism of TAM differentiation is unclear. We investigated factors involved in the differentiation of monocytes into TAMs within the tumor microenvironment of triple-negative breast cancer (TNBC). We screened 172 compounds and found that a heat shock protein 90 (HSP90) inhibitor blocked TNBC-induced monocyte-to-TAM differentiation in human monocytes THP-1. TNBC-derived conditional medium (CM) activated cell signaling pathways, including MAP kinase, AKT and STAT3, and increased the expression of TAM-related genes and proteins. These inductions were suppressed by HSP90 inhibition or by knockdown of HSP90 in TNBC. Additionally, we confirmed that TNBC secreted HSP90 extracellularly and that HSP90 itself promoted TAM differentiation. In a mouse tumor model, treatment with an HSP90 inhibitor suppressed tumor growth and reduced TAMs in the tumor microenvironment. Our findings demonstrate the role of HSP90 in TAM differentiation, suggesting HSP90 as a potential target for TNBC immunotherapy due to its regulatory role in monocyte-to-TAM differentiation.

Abstract The oral administration of antioxidants may suppress UV-B-induced skin damage. HITHION YH-15, the extract of Torula yeast (Cyberlindnera jadinii), is rich in cysteine-containing peptides such as reduced and oxidized glutathione (GSH and GSSG), γ-glutamylcysteine (γ-Glu-Cys), and cysteinylglycine (Cys-Gly). These four constituents are termed cysteine peptides. In this study, we investigated the protective effects of cysteine peptides against UV-B in a randomized, placebo-controlled, double-blind, parallel-group study. A total of 90 healthy males and females aged 30–59 years were enrolled and randomized into two groups of 45 individuals each (cysteine peptides (48 mg/day) and placebo). Changes in UV-B-induced erythema and pigmentation were compared between groups after 5 weeks of test food intake. The minimal erythema dose (MED) significantly increased (*p = 0.019) in the cysteine peptides group compared to that in the placebo group, indicating suppression of UV-B-induced erythema. ΔL* value significantly increased (***p

Severe pulmonary vasoconstriction induced by protamine is a rare complication. We report a case of a 77-year-old male patient with a history of mitral valve plasty (MVP). He underwent redo MVP via right thoracotomy under the totally endoscopic procedure (MICS redo-MVP). Immediately after weaning cardiopulmonary bypass (CPB), protamine was administrated. 10 min later peak systolic pulmonary arterial pressure (sys PAP) rose to 62 mmHg, and 30 min later to 80 mmHg. Due to the negative impact of protamine administration, nitric oxide inhalation (iNO) therapy was started with a concentration of 20 ppm. 10 min after iNO therapy started, sys PAP decreased to 63 mmHg. After entering the intensive care unit (ICU), sys PAP decreased to 35 mmHg. Here, we present an effective iNO therapy case for pulmonary hypertension due to protamine and the patient had a good postoperative recovery. This study was approved by the Institutional Review Board at Kitaharima Medical Center (IRB-0602) with the waiver of informed consent.

Abstract The onset and progression mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are being studied. We developed and analyzed a new mouse model of obesity by combining maternal Id-like molecule (Maid) and melanocortin-4 receptor (Mc4r) gene deletions. Four mice, each at 12 and 28 weeks of age, were analyzed for each genotype: Maid gene knockout, Mc4r gene knockout, combined Mc4r and Maid gene knockout, and Mc4r gene knockout with a high-fat diet. Mice with a combined deficiency of Mc4r and Maid gene showed significantly more severe obesity compared to all other genotypes, but no liver fibrosis or a decline in metabolic status were observed. In visceral white adipose tissue, Maid and Mc4r gene knockout mice had fewer CD11c-positive cells and lower mRNA expression of both inflammatory and anti-inflammatory cytokines. Furthermore, Maid and Mc4r gene knockout mice showed lower expression of adipocytokines in visceral white adipose tissue and uncoupling protein-1 in scapular brown adipose tissue. The expression of adipocytokines and uncoupling protein-1 is regulated by sympathetic nerve signaling that contribute severe obesity in Maid and Mc4r gene knockout mice. These mechanisms contribute hyperobesity in Maid and Mc4r gene knockout mice.

Abstract The pathophysiology of variant transthyretin (TTR) amyloidosis (ATTRv) is associated with destabilizing mutations in the TTR tetramer. However, why TTR with a wild-type genetic sequence misfolds and aggregates in wild-type transthyretin amyloidosis (ATTRwt) is unknown. Here, we evaluate kinetic TTR stability with a newly developed ELISA system in combination with urea-induced protein denaturation. Compared with that in control patients, endogenous TTR in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) exhibited thermodynamic instability, indicating that circulating TTR instability may be associated with the pathogenesis of ATTRwt as well as ATTRv. Our findings provide new insight into the underlying mechanisms of ATTRwt.

Abstract The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents’ decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents’ decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89–0.99; Model 2: 0.95 0.90–0.997). Critical disease (5.25; 1.09–25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21–14.53; Model 2: 5.47, 1.50–19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14–2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility.

We calculated attack rates for household contacts of COVID-19 patients during the SARS-CoV-2 Omicron BA.2–dominant period in Japan. Attack rates among household contacts without recent (

Abstract Condylar resorption occurs in some cases after orthognathic surgery, and the risk factors associated with postoperative condylar head resorption have been extensively described. Nevertheless, even in cases with a combination of risk factors, postoperative condylar resorption may not appear. This study analyzed the microstructure and three-dimensional positional change of the condylar bone via imaging in patients who have undergone bimaxillary orthognathic surgery to determine whether the microstructure or condylar position differs between patients with and without postoperative condylar resorption. Among asymptomatic patients who underwent bimaxillary surgery between April 2021 and March 2022 at our department, 17 patients were analyzed, limited to “female,” “skeletal Class II,” and “high-angle cases,” which are known risk factors for mandibular head resorption. Multidetector computed tomography was performed on these patients before and 6 months after surgery, and the bone microstructure of the condylar head and the three-dimensional positional changes of the condylar bone and the proximal bony fragments were compared with the presence of postoperative condyle resorption using the bone morphology software TRI/3D-BON. Patients with condylar bone abnormalities before surgery and those with high trabecular bone density can develop postoperative resorption if the condyle is misaligned by surgery.

Abstract Impaired insulin secretory capacity is associated with high glycemic variability in patients with type 2 diabetes (T2DM). However, there are no existing reports on the association between insulin secretory capacity and time in range (TIR). This retrospective study involved 330 T2DM admitted for diabetes education who underwent intermittently scanned continuous glucose monitoring (isCGM) and had their fasting serum C-peptide immunoreactivity (S-CPR) measured within 5 days of admission. The baseline characteristics were as follows: age, 60.2 years; glycated hemoglobin (HbA1c), 9.2%; S-CPR, 2.2 ng/mL; S-CPR index (S-CPR [ng/mL]/fasting plasma glucose [mg/dL] × 100), 1.6; and TIR, 60.3%. TIR correlated significantly with the S-CPR index, which was confirmed by multivariate analysis that included various factors such as HbA1c. Receiver operating characteristic (ROC) analysis showed that 1.88 was the optimal S-CPR index level to predict TIR ≥ 70%. In addition to HbA1c and biguanide use, the S-CPR index was a significant factor associated with TIR > 70%. S-CPR index values of ≥ 1.88 also correlated significantly with TIR > 70%. In conclusion, insulin secretory capacity is associated with TIR in Japanese T2DM, suggesting that the S-CPR index might be a potentially useful biomarker insulin secretory capacity, in association with TIR. Trial registration UMIN0000254333.

Abstract Allogeneic bone grafts are used to treat bone defects in orthopedic surgery, but the osteogenic potential of artificial bones remains a challenge. In this study, we developed a β-tricalcium phosphate (β-TCP) formulation containing MgO, ZnO, SrO, and SiO2 and compared its bone-forming ability with that of β-TCP without biological elements. We prepared β-TCP discs with 60% porosity containing 1.0 wt% of these biological elements. β-TCP scaffolds were loaded with bone marrow-derived mesenchymal stem cells (BMSC) from 7-week-old male rats and cultured for 2 weeks. ALP activity and mRNA expression of osteogenic markers were evaluated. In addition, scaffolds were implanted subcutaneously in rats and analyzed after 7 weeks. In vitro, the MgO group showed lower Ca concentrations and higher osteogenic marker expression compared to controls. In vivo, the MgO group showed higher ALP activity compared to controls, and RT-qPCR analysis showed significant expression of BMP2 and VEGF. Histopathology, fluorescent immunostaining, and micro-CT also showed relatively better bone formation in the MgO group. β-TCP with MgO may enhance bone morphology in vitro and in vivo and improve the prognosis of patients with substantial and refractory bone defects.

Abstract This study aims to investigate the influence of lumbar spine disorders on the development of asymmetric hallux valgus (HV). Data from the fifth survey of the Osteoarthritis/Osteoporosis Against Disability (ROAD) study, a nationwide prospective study in Japan, were analyzed. HV severity was categorized into 4 grades based on the radiographic HV angle, and asymmetric HV was defined as having at least one HV on either side, with a difference of two or more severity grades between the left and right. Controls were matched from both the Normal group (without HV on both sides) and the Symmetric group (HV on at least one side with a difference of one or less severity grades). Univariate analysis assessed lumbar conditions, and multinomial logistic regression analysis explored the association between lumbar spine disorders and asymmetric HV. Among 1997 participants, 27 had asymmetric HV. Univariate analysis revealed a higher incidence of L5 spondylolisthesis and scoliosis in the Asymmetric group. Multinomial logistic regression analysis revealed that scoliosis independently increased the likelihood of asymmetrical HV (Odds ratio [OR] = 3.586, 95%Confidence interval [CI] 1.111–11.582), but showed no significant impact on symmetrical HV (OR 0.910, 95% CI 0.355–2.334). Asymmetric HV is rare but may be associated with lumbar spine disorders, particularly scoliosis.

Abstract Epithelial ovarian cancer (EOC) is widely recognized as the most lethal gynecological malignancy; however, its early-stage detection remains a considerable clinical challenge. To address this, we have introduced a new method, named Comprehensive Serum Glycopeptide Spectral Analysis (CSGSA), which detects early-stage cancer by combining glycan alterations in serum glycoproteins with tumor markers. We detected 1712 glycopeptides using liquid chromatography–mass spectrometry from the sera obtained from 564 patients with EOC and 1149 controls across 13 institutions. Furthermore, we used a convolutional neural network to analyze the expression patterns of the glycopeptides and tumor markers. Using this approach, we successfully differentiated early-stage EOC (Stage I) from non-EOC, with an area under the curve (AUC) of 0.924 in receiver operating characteristic (ROC) analysis. This method markedly outperforms conventional tumor markers, including cancer antigen 125 (CA125, 0.842) and human epididymis protein 4 (HE4, 0.717). Notably, our method exhibited remarkable efficacy in differentiating early-stage ovarian clear cell carcinoma from endometrioma, achieving a ROC-AUC of 0.808, outperforming CA125 (0.538) and HE4 (0.557). Our study presents a promising breakthrough in the early detection of EOC through the innovative CSGSA method. The integration of glycan alterations with cancer-related tumor markers has demonstrated exceptional diagnostic potential.

Abstract Because hepatic stellate cells (HSCs) play a major role in fibrosis, we focused on HSCs as a potential target for the treatment of liver fibrosis. In this study, we attempted to identify drug candidates to inactivate HSCs and found that several proteasome inhibitors (PIs) reduced HSC viability. Our data showed that a second-generation PI, carfilzomib (CZM), suppressed the expression of fibrotic markers in primary murine HSCs at low concentrations of 5 or 10 nM. Since CZM was not toxic to HSCs up to a concentration of 12.5 nM, we examined its antifibrotic effects further. CZM achieved a clear reduction in liver fibrosis in the carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis without worsening of liver injury. Mechanistically, RNA sequence analysis of primary HSCs revealed that CZM inhibits mitosis in HSCs. In the CCl4-injured liver, amphiregulin, which is known to activate mitogenic signaling pathways and fibrogenic activity and is upregulated in murine and human metabolic dysfunction-associated steatohepatitis (MASH), was downregulated by CZM administration, leading to inhibition of mitosis in HSCs. Thus, CZM and next-generation PIs in development could be potential therapeutic agents for the treatment of liver fibrosis via inactivation of HSCs without liver injury.

Abstract The COVID-19 pandemic has increased germ aversion, an aversive affective response to a high likelihood of pathogen transmission. While psychological factors are associated with chronic pain, the relationship between germ aversion and chronic pain remains unexplored. This study aimed to examine the relationship between germ aversion and new-onset and prognosis of chronic pain using longitudinal data collected during the COVID-19 pandemic. We conducted web-based surveys of full-time workers at baseline and after three months. Data were collected on demographic characteristics, psychological factors, and chronic pain. Germ aversion was assessed using a modified Perceived Vulnerability to Disease scale. We analyzed responses from 1265 panelists who completed the survey twice. The prevalence of chronic low back pain (CLBP) and chronic neck and shoulder pain (CNSP) was associated with sex, short sleep duration, psychological distress, loneliness, and germ aversion. Stratified analyses showed that germ aversion was a risk factor for CLBP at three months in both individuals with and without CLBP at baseline, and for CNSP at three months in those with CNSP at baseline, even after adjustment for confounders. In conclusion, this preliminary study suggests that high germ aversion is a risk factor for CLBP and CNSP in young and middle-aged workers.

Abstract This paper presents a novel computational design and fabrication method for fabric-based soft pneumatic actuators (FSPAs) that use Turing patterns, inspired by Alan Turing’s morphogenesis theory. These inflatable structures can adapt their shapes with simple pressure changes and are applicable in areas like soft robotics, airbags, and temporary shelters. Traditionally, the design of such structures relies on isotropic materials and the designer’s expertise, often requiring a trial-and-error approach. The present study introduces a method to automate this process using advanced numerical optimization to design and manufacture fabric-based inflatable structures with programmable shape-morphing capabilities. Initially, an optimized distribution of the material orientation field on the surface membrane is achieved through gradient-based orientation optimization. This involves a comprehensive physical deployment simulation using the nonlinear shell finite element method, which is integrated into the inner loop of the optimization algorithm. This continuous adjustment of material orientations enhances the design objectives. These material orientation fields are transformed into discretized texture patterns that replicate the same anisotropic deformations. Anisotropic reaction-diffusion equations, using diffusion coefficients determined by local orientations from the optimization step, are then utilized to create space-filling Turing pattern textures. Furthermore, the fabrication methods of these optimized Turing pattern textures are explored using fabrics through heat bonding and embroidery. The performance of the fabricated FSPAs is evaluated through three different deformation shapes: C-shaped bending, S-shaped bending, and twisting.

Abstract Cervical radiculopathy might affect finger movement and dexterity. Postoperative features and clinical outcomes comparing C8 radiculopathies with other radiculopathies are unknown. This prospective multicenter study analyzed 359 patients undergoing single-level surgery for pure cervical radiculopathy (C5, 48; C6, 132; C7, 149; C8, 30). Background data and pre- and 1-year postoperative neck disability index (NDI) and numerical rating scale (NRS) scores were collected. The C5–7 and C8 radiculopathy groups were compared after propensity score matching, with clinical significance determined by minimal clinically important differences (MCID). Postoperative arm numbness was significantly higher than upper back or neck numbness, and arm pain was reduced the most (3.4 points) after surgery among the C5–8 radiculopathy groups. The C8 radiculopathy group had worse postoperative NDI scores (p = 0.026), upper back pain (p = 0.042), change in arm pain NRS scores (p = 0.021), and upper back numbness (p = 0.028) than the C5–7 group. NDI achieved MCID in both groups, but neck and arm pain NRS did not achieve MCID in the C8 group. In conclusion, although arm numbness persisted, arm pain was relieved after surgery for cervical radiculopathy. Patients with C8 radiculopathy exhibited worse NDI and change in NRS arm pain score than those with C5–7 radiculopathy.

Abstract Cell therapy for adrenocortical insufficiency can potentially provide steroid replacement in response to physiological stimuli. Previously, we reported that adipose tissue-derived stromal cells (ADSCs) are transformed into steroid-producing cells by overexpression of nuclear receptor subfamily 5 group A member 1 (NR5A1). The steroidogenic cells are characterized by the production of both adrenal and gonadal steroids. Cytotherapy for adrenocortical insufficiency requires cells with more adrenocortical characteristics. Considering the highly developed vascular network within the adrenal cortex, all adrenocortical cells are adjacent to and interact with vascular endothelial cells (VECs). In this study, NR5A1-induced steroidogenic cells derived from mouse ADSCs (NR5A1-ADSCs) were co-cultured with mouse VECs. Testosterone secretion in NR5A1-ADSCs was not altered; however, corticosterone secretion significantly increased while levels of steroidogenic enzymes significantly increased in the corticosterone synthesis pathway. Co-culture with lymphatic endothelial cells (LECs) or ADSCs, or transwell culture with NR5A1-ADSCs and VECs did not alter corticosterone production. VECs expressed higher levels of collagen and laminin than LECs. Culture in type-IV collagen and laminin-coated dishes increased corticosterone secretion in NR5A1-ADSCs. These results suggest that VECs may characterize ADSC-derived steroidogenic cells into a more corticosterone-producing phenotype, and VECs may be useful for generating adrenal steroidogenic cells from stem cells.

Abstract Background Prostate ductal adenocarcinoma, a rare histology observed in 0.4–0.8% of all prostate cancers, is treated similarly to acinar adenocarcinoma but tends to have a higher likelihood of metastasis, recurrence, and poorer prognosis. Case presentation A 73-year-old Asian-Japanese male presented with gross hematuria, with investigations revealing a prostate ductal adenocarcinoma. Subsequent radical prostatectomy indicated a Gleason score of 8 with no lymph node metastasis. Despite initial prostate-specific antigen level reductions post-prostatectomy and salvage radiation therapy due to recurring elevated prostate-specific antigen levels, no recurrence was evident until 13 years later. A tumor in the anterior urethra was identified as metastasis of his prostate ductal adenocarcinoma. Conclusion This report presents an uncommon case of prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-radical prostatectomy.

Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality. Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders, which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries. Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases. In this review, we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations, epidemiology, and aberrant cellular composition involving the biliary ductules, cholangiocytes, immune system, fibroblasts, and the microbiome. We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies. This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.