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This study introduces a novel microfluidic polymer chip system that employs an embedded anionic surfactant (AS) ion-selective fluorescence optode (AS fluorescence optode) as a detector for measuring AS. The AS fluorescent optode comprises a lactone form of rhodamine B (L-RB) embedded in 2-nitrophenyl octyl ether plasticized poly (vinyl chloride) membrane. The AS fluorescence optode demonstrated a linear correlation between fluorescence intensity peak heights and AS concentrations within the range of less than 20 µM under optimal flow conditions. The limit of detection for AS was approximately 0.06 µM. The microfluidic system was utilized to measure AS levels in environmental samples, such as river water and tap water., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Clinical studies have demonstrated that IL-4, a type 2 cytokine, plays an important role in the pathogenesis of chronic rhinosinusitis and eosinophilic asthma. However, the direct effect of IL-4 on eosinophils remains unclear., Objective: We aimed to elucidate the inflammatory effects of IL-4 on the functions of human eosinophils., Methods: A multiomics analysis comprising transcriptomics, proteomics, lipidomics, quantitative RT-PCR, and flow cytometry was performed by using blood eosinophils from healthy subjects stimulated with IL-4, IL-5, or a combination thereof., Results: Transcriptomic and proteomic analyses revealed that both IL-4 and IL-5 upregulate the expression of γ-gultamyl transferase 5, a fatty acid-metabolizing enzyme that converts leukotriene C 4 into leukotriene D 4 . In addition, IL-4 specifically upregulates the expression of IL-1 receptor-like 1 (IL1RL1), a receptor for IL-33 and transglutaminase-2. Additional transcriptomic analysis of cells stimulated with IL-13 revealed altered gene expression profiles, characterized by the upregulation of γ-gultamyl transferase 5, transglutaminase-2, and IL1RL1. The IL-13-induced changes were not totally different from the IL-4-induced changes. Lipidomic analysis revealed that IL-5 and IL-4 additively increased the extracellular release of leukotriene D 4 . In vitro experiments revealed that STAT6 and IL-4 receptor-α control the expression of these molecules in the presence of IL-4 and IL-13. Analysis of eosinophils derived from patients with allergic disorders indicated the involvement of IL-4 and IL-13 at the inflamed sites., Conclusions: IL-4 induces the proallergic phenotype of IL1RL1 high eosinophils, with prominent cysteinyl leukotriene metabolism via STAT6. These cellular changes represent potential therapeutic targets for chronic rhinosinusitis and eosinophilic asthma., Competing Interests: Disclosure statement Supported by the Japanese Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research Program (KAKENHI) (grants 15H05897, 15H05898, and 20H00495 [to M.A.]), Japan Science and Technology Agency program Exploratory Research for Advanced Technology (JST-ERATO) (grant JPMJER2101 [to M.A.]), Research Grant on Allergic Disease and Immunology from the Japan Agency for Medical Research and Development (grant 22ek0410097 [to J.M.]), JSPS Grant-in-Aid for Young Scientists (grant 20K17239 [to J.M.]), RIKEN Special Postdoctoral Researchers Program (to J.M.), GSK Japan Research Grant 2018 (to J.M.), and Grant-in-Aid for Research of the ONO Medical Research Foundation (to J.M.). Disclosure of potential conflict of interest: J. Miyata, K. Masaki, H. Kabata, and K. Fukunaga report receiving research grant support from GSK and AstraZeneca. J. Miyata and K. Fukunaga report receiving payments for lectures from GSK, AstraZeneca, and Sanofi. K. Masaki reports receiving payments for lectures from GSK and AstraZeneca, and GSK. H. Kabata reports receiving payments for lectures from AstraZeneca and Sanofi. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Meconium, a non-invasive biomaterial reflecting prenatal substance accumulation, could provide valuable insights into neonatal health. However, the comprehensive protein profile of meconium across gestational ages remains unclear. Here, we conducted an extensive proteomic analysis of first meconium from 259 newborns across varied gestational ages to delineate protein composition and elucidate its relevance to neonatal diseases. The first meconium samples were collected, with the majority obtained before feeding, and the mean time for the first meconium passage from the anus was 11.9 ± 9.47 h. Our analysis revealed 5370 host-derived meconium proteins, which varied depending on sex and gestational age. Specifically, meconium from preterm infants exhibited elevated concentrations of proteins associated with the extracellular matrix. Additionally, the protein profiles of meconium also exhibited unique variations depending on both specific diseases, including gastrointestinal diseases, congenital heart diseases, and maternal conditions. Furthermore, we developed a machine learning model to predict gestational ages using meconium proteins. Our model suggests that newborns with gastrointestinal diseases and congenital heart diseases may have immature gastrointestinal systems. These findings highlight the intricate relationship between clinical parameters and meconium protein composition, offering potential for a novel approach to assess neonatal gastrointestinal health., (© 2024. The Author(s).)

Recent advances in in-depth data-independent acquisition proteomic analysis have enabled comprehensive quantitative analysis of >10,000 proteins. Herein, an integrated proteogenomic analysis for inherited bone marrow failure syndrome (IBMFS) was performed to reveal their biological features and to develop a proteomic-based diagnostic assay in the discovery cohort; dyskeratosis congenita (n = 12), Fanconi anemia (n = 11), Diamond-Blackfan anemia (DBA, n = 9), Shwachman-Diamond syndrome (SDS, n = 6), ADH5/ALDH2 deficiency (n = 4), and other IBMFS (n = 18). Unsupervised proteomic clustering identified eight independent clusters (C1-C8), with the ribosomal pathway specifically downregulated in C1 and C2, enriched for DBA and SDS, respectively. Six patients with SDS had significantly decreased SBDS protein expression, with two of these not diagnosed by DNA sequencing alone. Four patients with ADH5/ALDH2 deficiency showed significantly reduced ADH5 protein expression. To perform a large-scale rapid IBMFS screening, targeted proteomic analysis was performed on 417 samples from patients with IBMFS-related hematological disorders (n = 390) and healthy controls (n = 27). SBDS and ADH5 protein expressions were significantly reduced in SDS and ADH5/ALDH2 deficiency, respectively. The clinical application of this first integrated proteogenomic analysis would be useful for the diagnosis and screening of IBMFS, where appropriate clinical screening tests are lacking., (© 2024. The Author(s).)

Mapping protein interaction complexes in their natural state in vivo is arguably the Holy Grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused on this. This may, however, be solved by artificial intelligence (AI) and proteomics. Here, we describe the development of HaloTag-based affinity purification mass spectrometry (HaloMS), a high-throughput HaloMS assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assays. As a proof-of-principle, we used HaloMS to evaluate the protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using an in vitro pull-down assay and AI-based prediction tools. Applying HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor (TF)-protein complexes, revealing proteome-wide human adipocyte TF networks and shedding light on how different pathways are integrated., (© The Author(s) 2024. Published by Oxford University Press.)

Recent studies have highlighted the significance of cellular metabolism in the initiation of clonal expansion and effector differentiation of T cells. Upon exposure to antigens, naïve CD4 + T cells undergo metabolic reprogramming to meet their metabolic requirements. However, only few studies have simultaneously evaluated the changes in protein and metabolite levels during T cell differentiation. Our research seeks to fill the gap by conducting a comprehensive analysis of changes in levels of metabolites, including sugars, amino acids, intermediates of the TCA cycle, fatty acids, and lipids. By integrating metabolomics and proteomics data, we discovered that the quantity and composition of cellular lipids underwent significant changes in different effector Th cell subsets. Especially, we found that the sphingolipid biosynthesis pathway was commonly activated in Th1, Th2, Th17, and iTreg cells and that inhibition of this pathway led to the suppression of Th17 and iTreg cells differentiation. Additionally, we discovered that Th17 and iTreg cells enhance glycosphingolipid metabolism, and inhibition of this pathway also results in the suppression of Th17 and iTreg cell generation. These findings demonstrate that the utility of our combined metabolomics and proteomics analysis in furthering the understanding of metabolic transition during Th cell differentiation., (© 2024. The Author(s).)

This umbrella review aimed to examine and synthesize qualitative studies that explored the barriers and facilitators of advance care planning for persons with dementia, their families, and their healthcare professionals and caregivers. The modified umbrella review approach developed by the Joanna Briggs Institute was followed. Five major English databases were searched. Four reviews based on 38 primary qualitative studies were included. The methodological quality of the included reviews was moderate to high. The synthesis yielded 16 descriptive themes and five analytical themes: making the wishes/preferences of persons with dementia visible; constructive collaboration based on stakeholders having positive relationships; emotional chaos in facing end-of-life substitute decision-making; initiating the advance care planning process; and preparedness and commitment of healthcare providers to advance care planning. Comprehensive and workable strategies are required to overcome complex and interrelated barriers involving not only healthcare professionals but also organizational and systemic challenges., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study investigated the relationship between Denonvilliers' fascia (DF) and the pelvic plexus branches in women and explored the possibility of using the DF as a positional marker in nerve-sparing radical hysterectomy (RH)., Methods: This study included eight female cadavers. The DF, its lateral border, and the pelvic autonomic nerves running lateral to the DF were dissected and examined. The pelvis was cut into two along the mid-sagittal line. The uterine artery, deep uterine veins, vesical veins, and nerve branches to the pelvic organs were carefully dissected., Results: The nerves ran sagitally, while the DF ran perpendicularly to them. The rectovaginal ligament was continuous with the DF, forming a single structure. The DF attached perpendicularly and seamlessly to the pelvic plexus. The pelvic plexus branches were classified into a ventral part branching to the bladder, uterus, and upper vagina and a dorsal part branching to the lower vagina and rectum as well as into four courses. Nerves were attached to the rectovaginal ligament and ran on its surface to the bladder ventral to the DF. The uterine branches split from the common trunk of these nerves. The most dorsal branch to the bladder primarily had a common trunk with the uterine branch, which is the most important and should be preserved in nerve-sparing Okabayashi RH., Conclusion: The DF can be used as a marker for nerve course, particularly in one of the bladder branches running directly superior to the DF, which can be preserved in nerve-sparing Okabayashi RH., Competing Interests: Declaration of competing interest KC received lecture honoraria from Ethicon (Tokyo, Japan), Terumo (Tokyo, Japan), and Chugai Pharmaceutical Co. (Tokyo, Japan). KI received lecture honoraria from AstraZeneca (Tokyo, Japan). RK received research funds from Yakult Pharmaceutical Industry Co. (Tokyo, Japan) and Chugai Pharmaceutical Co. (Tokyo, Japan) and lecture honoraria from Japan Vaccine Co. (Tokyo, Japan), MSD Japan (Tokyo, Japan), and Chugai Pharmaceutical Co. (Tokyo, Japan). SM, KY, and KA declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Music is present in every known society but varies from place to place. What, if anything, is universal to music cognition? We measured a signature of mental representations of rhythm in 39 participant groups in 15 countries, spanning urban societies and Indigenous populations. Listeners reproduced random 'seed' rhythms; their reproductions were fed back as the stimulus (as in the game of 'telephone'), such that their biases (the prior) could be estimated from the distribution of reproductions. Every tested group showed a sparse prior with peaks at integer-ratio rhythms. However, the importance of different integer ratios varied across groups, often reflecting local musical practices. Our results suggest a common feature of music cognition: discrete rhythm 'categories' at small-integer ratios. These discrete representations plausibly stabilize musical systems in the face of cultural transmission but interact with culture-specific traditions to yield the diversity that is evident when mental representations are probed across many cultures., (© 2024. The Author(s).)

Objective: The classic Okabayashi nerve-sparing radical hysterectomy involves complete resection of the posterior leaf of the vesicouterine ligament, whereas in the simplified nerve-sparing radical hysterectomy, only the vesical veins and some connective tissue of the posterior layer of the vesicouterine ligament are resected. This study aimed to compare bladder function and cervical carcinoma relapse-free survival between these two techniques., Methods: We conducted a retrospective, historical control study. All female patients aged >20 years who were diagnosed with cervical cancer stage IB1-IIB and underwent radical hysterectomy with pelvic lymphadenectomy between 2009 and 2022 were enrolled. Patients who had a history of other cancers and those who were treated with non-surgical approaches or non-radical hysterectomy were excluded. The primary outcome was relapse-free survival during the follow-up period., Results: A total of 114 patients who underwent curative-intent radical hysterectomy were included in this study. The median follow-up duration was 60 months. No significant difference was observed in relapse-free survival between the two surgical procedures. The simplified nerve-sparing radical hysterectomy was superior in terms of both motor and sensory bladder function outcomes., Conclusion: Resection of the posterior layer of the vesicouterine ligament, with the procedure limited to the vesical veins, is an effective and safe method for radical hysterectomy. It may be more useful for preserving the bladder function, without leading to unfavorable oncologic outcomes., Competing Interests: K. Chikazawa received lecture honoraria from Ethicon (Tokyo, Japan), Terumo (Tokyo, Japan) and Chugai Pharmaceutical Co. (Tokyo, Japan). K. Imai received lecture honoraria from AstraZeneca (Tokyo, Japan). R. Konno received research funds from Yakult Pharmaceutical Industry Co. (Tokyo, Japan) and Chugai Pharmaceutical Co. (Tokyo, Japan) and lecture honoraria from Japan Vaccine Co. (Tokyo, Japan), MSD Japan (Tokyo, Japan), and Chugai Pharmaceutical Co. (Tokyo, Japan). The fourth author declares no conflict of interest. The funding organizations did not contribute to any aspect of conducting or reporting this study., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

In recent years, there has been a growing demand for low-input proteomics, particularly in the context of single-cell proteomics (SCP). In this study, we have developed a lauryl maltose neopentyl glycol (LMNG)-assisted sample preparation (LASP) method. This method effectively reduces protein and peptide loss in samples by incorporating LMNG, a surfactant, into the digestion solution and subsequently removing the LMNG simply via reversed phase solid-phase extraction. The advantage of removing LMNG during sample preparation for general proteomic analysis is the prevention of mass spectrometry (MS) contamination. When we applied the LASP method to the low-input SP3 method and on-bead digestion in coimmunoprecipitation-MS, we observed a significant improvement in the recovery of the digested peptides. Furthermore, we have established a simple and easy sample preparation method for SCP based on the LASP method and identified a median of 1175 proteins from a single HEK239F cell using liquid chromatography (LC)-MS/MS with a throughput of 80 samples per day., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: CS is deputy editor in chief of JBI Evidence Synthesis. LL is a paid employee of JBI, The University of Adelaide. LL and CS are co-conveners of the JBI Mixed Methods Systematic Review Methodology Group. The other authors declare no conflicts of interest.

Objective: This review update aimed to determine the best strategies for assisted bathing or showering for older adults with dementia., Introduction: Assisted bathing is a high-risk activity, as it can trigger agitated behaviors. Assisted bathing of older adults with dementia can create caregiver challenges and stress., Inclusion Criteria: This review update considered quantitative, qualitative, and mixed methods studies that investigated, firstly, older adults with dementia who required assistance with bathing and, secondly, their caregivers and family members who provided this assistance. The quantitative component considered randomized controlled trials and quasi-experimental studies testing interventions for reducing agitated behaviors in older adults with dementia during bathing, as well as perceived confidence or satisfaction in caregivers. The qualitative component considered studies that reported on experiences of clients or caregivers during the bathing process., Methods: A JBI mixed methods review was conducted following the convergent segregated approach. The review considered studies published between 1990 and March 11, 2022. The databases searched were PubMed, CINAHL, and Embase. Gray literature was also searched. Two independent reviewers screened titles and abstracts. Full texts were retrieved for studies that met the inclusion criteria and were assessed further for eligibility. Two reviewers independently assessed the quality of included studies and extracted data using the standardized JBI tools. Due to methodological and clinical heterogeneity, the results were presented narratively in the quantitative section. For the qualitative component, meta-synthesis was conducted following the JBI approach of meta-aggregation. Finally, evidence from the 2 components was integrated following the convergent segregated approach., Results: Ten quantitative and 4 qualitative studies were included. The methodological quality was poor to moderate in the quantitative studies and moderate to high in the qualitative studies. Results from 3 quantitative studies suggested that providing training to caregivers on person-centered bathing reduced agitated behaviors in older adults with dementia. Other interventions did not show conclusive evidence of their effectiveness in any outcomes of interest. Two synthesized findings highlighted i) the importance of working within each person's reality by having the skills and knowledge required to deliver person-centered assistance and ii) the challenges experienced by caregivers, such as lack of support, time pressure, and safety-related fears. The integrated evidence showed that the quantitative and qualitative components complemented each other to promote the training of caregivers to deliver person-centered bathing., Discussion: Integrated findings can help inform an evidence-based strategy utilizing a person-centered bathing approach to reduce agitated behaviors in older adults with dementia. Due to the limited number of eligible studies, and the clinical and methodological heterogeneity of included quantitative studies, no statistical pooling was possible. More studies are needed, particularly intervention studies with high methodological quality., Conclusions: This review update suggests that providing caregivers with person-centered bathing training should be encouraged prior to bathing older adults with dementia. Caregivers should have the knowledge and skills, such as relevant assessment and communication skills, enabling them to provide effective bathing experiences to older adults living with dementia. Organizations should provide caregivers with appropriate resources and training for bathing older adults with dementia., Review Registration: PROSPERO CRD42020208048., Supplemental Digital Content: A Japanese-language version of the abstract of this review is available as supplemental digital content 1: http://links.lww.com/SRX/A37 ., Competing Interests: CS is deputy editor-in-chief of JBI Evidence Synthesis . LL is an academic staff member at JBI, The University of Adelaide. LL and CS are co-conveners of the JBI Mixed Methods Systematic Review Methodology Group. The other authors declare no conflicts of interest., (Copyright © 2023 JBI.)

Aims: This review aimed to explore and map the literature on sleep quality assessments of adults in care settings using non-wearable sleep trackers., Background: Sleep-monitoring technology is advancing, and sleep quality assessments using non-wearable sleep trackers can provide objective evidence for quality care., Design: This was a scoping review., Data Sources: Four electronic databases (PubMed, CINAHL, PsycInfo and Embase) were searched on 23 September 2022., Review Methods: This review followed the Joanna Briggs Institute's methodology and used the PRISMA-ScR checklist., Results: Thirty studies met our inclusion criteria. Sleep quality was assessed at home and in acute, non-acute and long-term care facilities. Physiological (heart rate and respiratory rate) and sleep parameters were assessed alone or in combination during patient care using non-wearable sleep trackers. Sleep parameters representing sleep quality varied across studies. Real-time monitoring with non-wearable sleep-tracking devices effectively shortened the length of hospital stay. However, studies investigating caregivers and nursing outcomes are lacking in the literature., Conclusion: Sleep quality assessments using non-wearable sleep trackers may facilitate the provision of quality care in home-based and clinical care settings. Future studies should focus on caregivers and care outcomes that could contribute to evidence-based nursing practice for sleep care in adults., (© 2024 John Wiley & Sons Australia, Ltd.)

Middle-down proteomics (MDP) is an analytical approach in which protein samples are digested with proteases such as Glu-C to generate large peptides (>3 kDa) that are analyzed by mass spectrometry (MS). This method is useful for characterizing high-molecular-weight proteins that are difficult to detect by top-down proteomics (TDP), in which intact proteins are analyzed by MS. In this study, we applied GeLC-FAIMS-MS, a multidimensional separation workflow that combines gel-based prefractionation with LC-FAIMS MS, for deep MDP. Middle-down peptides generated by optimized limited Glu-C digestion conditions were first size-fractionated by polyacrylamide gel electrophoresis, followed by C4 reversed-phase liquid chromatography separation and additional ion mobility fractionation, resulting in a significant increase in peptide length detectable by MS. In addition to global analysis, the GeLC-FAIMS-MS concept can also be applied to targeted MDP, where only proteins in the desired molecular weight range are gel-fractionated and their Glu-C digestion products are analyzed, as demonstrated by targeted analysis of integrins in exosomes. In-depth MDP achieved by global and targeted GeLC-FAIMS-MS supports the exploration of proteoform information not covered by conventional TDP by increasing the number of detectable protein groups or post-translational modifications (PTMs) and improving the sequence coverage., (© 2023 Wiley-VCH GmbH.)

Serum and plasma exhibit a broad dynamic range of protein concentrations, posing challenges for proteome analysis. Various technologies have been developed to reduce this complexity, including high-abundance depletion methods utilizing antibody columns, extracellular vesicle enrichment techniques, and trace protein enrichment using nanobead cocktails. Here, we employed lectins to address this, thereby extending the scope of biomarker discovery in serum or plasma using a novel approach. We enriched serum proteins using 37 different lectins and subjected them to LC-MS/MS analysis with data-independent acquisition. Solanum tuberosum lectin (STL) and Lycopersicon esculentum lectin (LEL) enabled the detection of more serum proteins than the other lectins. STL and LEL bind to N-acetylglucosamine oligomers, emphasizing the significance of capturing these oligomer-binding proteins when analyzing serum trace proteins. Combining STL and LEL proved more effective than using them separately, allowing us to identify over 3000 proteins from serum through single-shot proteome analysis. We applied the STL/LEL trace-protein enrichment method to the sera of systemic lupus erythematosus model mice. This revealed differences in >1300 proteins between the systemic lupus erythematosus model and control mouse sera, underscoring the utility of this method for biomarker discovery.

Background: Little is known about clinical or sociodemographic factors that influence health-related quality of life (HRQoL) in patients with adult congenital heart disease (ACHD).Methods and Results: We conducted a nationwide prospective cross-sectional multicenter study at 4 large ACHD centers in Japan. From November 2016 to June 2018, we enrolled 1,223 ACHD patients; 1,025 patients had an HRQoL score. Patients completed a questionnaire survey, including sociodemographic characteristics, and the 36-Item Short-Form Health Survey (SF-36). To determine factors associated with HRQoL, correlations between 2 SF-36 summary scores (i.e., physical component score [PCS] and mental component score [MCS]) and other clinical or sociodemographic variables were examined using linear regression analysis. In multivariable analysis, poorer PCS was significantly associated with 11 variables, including older age, higher New York Heart Association class, previous cerebral infarction, being unemployed, and limited participation in physical education classes and sports clubs. Poorer MCS was associated with congenital heart disease of great complexity, being part of a non-sports club, current smoking, and social drinking. Student status and a higher number of family members were positively correlated with MCS., Conclusions: This study demonstrates that HRQoL in ACHD patients is associated with various clinical and sociodemographic factors. Further studies are needed to clarify whether some of these factors could be targets for future intervention programs to improve HRQoL outcomes.

Objectives: The clinical symptoms and complications of JDM differ depending on the type of muscle-specific autoantibodies (MSAs) present. We aimed to identify protein expression profiles specific for MSAs that characterize various clinical features by comprehensively analyzing the proteins present in the serum of patients with JDM., Methods: We analysed sera from patients with JDM that were positive for anti-melanoma differentiation-associated protein 5 (MDA5) antibodies (n = 5), anti-nuclear matrix protein 2 (NXP2) antibodies (n = 5) and anti-transcriptional intermediary factor 1 alpha or gamma subunit (TIF1-γ) antibodies (n = 5), and evaluated healthy controls (n = 5) via single-shot liquid chromatography-tandem mass spectrometry (MS) in data-independent acquisition mode, which is superior for comparative quantitative analysis. We identified different protein groups based on MSAs and performed pathway analysis to understand their characteristics., Results: We detected 2413 proteins from serum MS analysis; 508 proteins were commonly altered in MSAs, including many myogenic enzymes and IFN-regulated proteins. Pathway analysis using the top 50 proteins that were upregulated in each MSA group revealed that the type I IFN and proteasome pathways were significantly upregulated in the anti-MDA5 antibody group alone., Conclusion: Although JDM serum contains many proteins commonly altered in MSAs, the pathways associated with clinical features of MSAs differ based on protein accumulation. In-depth serum protein profiles associated with MSAs may be useful for developing therapeutic target molecules and biomarkers., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that is required for epithelial polarity. Knockout (KO) of membranous EBP50 (Me-EBP50) in ovarian clear cell carcinoma (OCCC) cells induced an epithelial-mesenchymal transition (EMT)-like phenotype, along with decreased proliferation, accelerated migration capability, and induction of cancer stem cell (CSC)-like properties. Shotgun proteomics analysis of proteins that co-immunoprecipitated with EBP50 revealed that Me-EBP50 strongly interacts with myosin 9 (MYH9). Specific inhibition of MYH9 with blebbistatin phenocopied Me-EBP50 KO, and blebbistatin treatment potentiated the effects of Me-EBP50 KO. In OCCC cells from clinical samples, Me-EBP50 and MYH9 were co-localized at the apical plasma membrane. Patients with a combination of Me-EBP50-high and MYH9-high scores had the best prognosis for overall and progression-free survival. Our data suggest that Me-EBP50 has tumor-suppressive effects through the establishment and maintenance of epithelial polarization. By contrast, loss of Me-EBP50 expression induces EMT-like phenotypes, probably due to MYH9 dysfunction; this results in increased cell mobility and enhanced CSC-like properties, which in turn promote OCCC progression., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

We studied the effect of cutaneous cold stimulus on the perceptual rating of musical chords. Despite the shown influence of music and tactile stimuli on human psychological evaluation, the effect of a cold stimulus on sound perception remains underexplored. We examined the effect of a cold stimulus on four psychological measures (frisson, arousal, pleasantness, and valence) as participants listened to two-note chords (consonance and dissonance). The cold-stimulus condition involved an experimenter touching the back of the participant's neck with a cooling device while listening to the sounds, while the control condition used a cooling device with the power off. For the frisson and arousal measures, the main effect of the stimulus condition was significant, showing that the cold stimulus increased the frisson and arousal measures. For the pleasantness and valence measures, there was a significant main effect of two-note chords, showing that a consonance was perceived as more pleasant than a dissonance; however, there was no significant main effect of stimulus condition, showing that the cold stimulus did not affect pleasantness and valence ratings. The results showed that a cold stimulus could bias frisson and arousal without affecting pleasantness and valence ratings when listening to musical sound.

Epithelial-mesenchymal transition is a hallmark of uterine carcinosarcoma (UCS). Here, shotgun proteomics analysis used to identify biomarkers associated with blebbistatin-mediated epithelial-mesenchymal transition in UCS indicated up-regulation of nucleobindin-2 (NUCB2) in endometrial carcinoma (Em Ca) cells. Expression of N-cadherin, Snail, Slug, and ZEB1 was reduced in NUCB2 knockout Em Ca cells, whereas ZEB1, Twist1, and vimentin were up-regulated in NUCB2-overexpressing Em Ca cells. NUCB2 knockout reduced cell proliferation and migration, whereas NUCB2 overexpression had the opposite effect. Treatment of Em Ca cells with transforming growth factor (TGF)-β1 dramatically altered morphology toward a fibroblastic appearance; concomitantly, expression of NUCB2 and ZEB1 increased. The NUCB2 promoter was also activated by transfection of Smad2. In UCS tissues, NUCB2 expression was significantly higher in sarcomatous compared with carcinomatous components, which was consistent with increased TGF-β1 mRNA expression in stromal and sarcomatous components compared with carcinomatous components. In addition, NUCB2 score correlated positively with ZEB1 and vimentin scores, whereas ZEB1 score correlated positively with Slug and vimentin scores and inversely with the E-cadherin score. Collectively, these data indicate that TGF-β-dependent up-regulation of NUCB2 and ZEB1 contributes to the phenotypic characteristics of sarcomatous components in UCS., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: KC received lecture honoraria from Ethicon (Tokyo, Japan), Terumo (Tokyo, Japan), and Chugai Pharmaceutical (Tokyo, Japan). RK received research funding from Yakult Pharmaceutical Industry (Tokyo, Japan) and Chugai Pharmaceutical (Tokyo, Japan), as well as lecture honoraria from Japan Vaccine (Tokyo, Japan), MSD Japan (Tokyo, Japan), and Chugai Pharmaceutical (Tokyo, Japan).

Background: Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of unknown etiology that affects the intra- and extrahepatic bile ducts. The present study examined the utility of a bile proteome analysis using a high-sensitivity mass spectrometer to comprehensively screen for novel PSC biomarkers., Methods: Bile endoscopically collected from patients with PSC, common bile duct stones, and biliary tract cancer were subjected to high-precision liquid chromatography/mass spectrometry. Some of the proteins specifically up-regulated in the bile of the PSC group were re-examined by an enzyme-linked immunosorbent assay., Results: A total of 8094 proteins were successfully identified and 332 were specifically up-regulated in the PSC group. The bioinformatics analysis showed that proteins involved in the proliferation and activation of diverse inflammatory cells were up-regulated in the PSC group. A receiver operating characteristic curve analysis showed good area under the curve values for interleukin-8 and annexin A1 (ANXA1) (0.836 and 0.914, respectively). Immunostaining for ANXA1 revealed its strong expression in inflammatory cells infiltrating the peripheral biliary tract in PSC livers., Conclusion: A bile proteome analysis is a useful tool for elucidating the pathogenesis of PSC and developing new diagnostic approaches. Therefore, ANXA1 has potential as a bile biomarker for PSC., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)