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The penis, the organ that bears reproductive and psychological importance, is susceptible to birth defects such as hypospadias or incomplete closure of urethra along the penis shaft. We discover that proper urethral closure in mouse embryos requires a unique mesenchymal cell population originated from outside of the penis. These "extragenital" cells, marked by a lineage marker Nr5a1 , migrate from the inguinal region into the embryonic penis and facilitate urethra closure by interacting with adjacent periurethral cells via the epidermal growth factor pathway. Ablation of Nr5a1 + cells leads to severe hypospadias and alters cell differentiation in the penis. This discovery highlights the indispensable role of Nr5a1 + extragenital cells in urethra closure, shedding light on the biology of penis formation and potential implications for human hypospadias.

Background: Aesthetic standards vary and are subjective; artificial intelligence (AI), which is currently seeing a boom in interest, has the potential to provide objective assessment., Objectives: The aim of this study was to provide a relatively objective assessment of the aesthetic outcomes of lower blepharoplasty-related surgeries, thereby enhancing the decision-making process and understanding of the surgical results., Methods: This study included 150 patients who had undergone lower blepharoplasty-related surgeries. Analysis was performed with FaceAge software, created by the authors' research team, which included 4 publicly available age estimation convolution neural network (CNN) models: Amazon Rekognition (Seattle, WA), Microsoft Azure Face (Redmond, WA), Face++ Detect (Beijing, China), and Inferdo face detection (New York, NY). This application was used to compare the subjects' real age and their age as estimated by the 4 CNNs. In addition, this application was used to estimate patient age based on preoperative and postoperative images of all 150 patients and to evaluate the effect of lower blepharoplasty., Results: In terms of accuracy in age prediction, all CNN models exhibited a certain degree of accuracy. For all 150 patients undergoing lower blepharoplasty-related surgeries, these surgeries resulted in about 2 years of rejuvenation with a statistically significant difference; for the sex difference, men had more age reduction than women also with a statistically significant difference; quadrilateral blepharoplasty showed the most significant antiaging effect., Conclusions: By using deep-learning models, lower blepharoplasty-related surgeries actually had an effect on perceived age reduction. Deep learning models have the potential to provide quantitative evidence for the rejuvenating effects of blepharoplasty and other cosmetic surgeries., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Previous studies have suggested that adamts9 (a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and is necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female-to-male sex conversion in late juvenile or adult zebrafish; however, primary sex determination was not affected in early juveniles of adamts9 KO. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicles) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex, and loss of adamts9 leads to defects in ovarian follicle development, female infertility, and sex conversion in late juveniles and mature adults. These results show that the ECM and extracellular metalloproteases play major roles in maintaining ovarian follicle development in zebrafish., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Various classification systems for tear trough deformity (TTD) have been published; however, their complexity can pose challenges in clinical use, especially for less experienced surgeons. It is believed that artificial intelligence (AI) technology can address some of these challenges by reducing inadvertent errors and improving the accuracy of medical practice. In this study, we aimed to establish a reliable and precise digital image grading model for TTD using smartphone-based photography enhanced using AI deep learning technology. This model is designed to aid and guide surgeons, particularly those who are less experienced or from younger generations, during clinical examinations and in making decisions regarding further surgical interventions., Materials and Methods: A total of 504 patients and 983 photos were included in the study. We adopted the Barton's grading system for TTD. All photos were taken using the same smartphone and processed and analyzed using the medical AI assistant (MAIA™) software. The photos were then randomly divided into two groups to establish training and testing models., Results: The confusion matrix for the training model demonstrated a sensitivity of 56%, specificity of 87.3%, F1 score of 0.57, and an area under the curve (AUROC) of 0.85. For the testing group, the sensitivity was 49.3%, specificity was 85%, F1 score was 0.49, and AUROC was 0.83. Representative heatmaps were also generated., Conclusion: Our study is the first to demonstrate that tear trough deformities can be easily categorized using a built-in smartphone camera in conjunction with an AI deep learning program. This approach can reduce errors during clinical patient evaluations, particularly for less experienced practitioners., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

In Brief: Female hypospadias is a little-known and poorly studied birth defect. This research establishes an anatomical and molecular foundation for future research to investigate the origins of this defect., Abstract: Hypospadias is a congenital anomaly of the external genitalia where the urethra does not properly close. In humans, hypospadias is mostly reported in male newborns, whereas in females hypospadias is rare, although it is generally considered to be under-reported. Improper urethra closure in the female genitalia can cause recurrent genitourinary tract infections and infertility. In mice, female hypospadias was induced by exposure to exogenous estrogenic compounds. Aside from the link between estrogen exposure and female hypospadias, the process of female urethra closure is largely unstudied, with the precise timing of urethra closure and associated molecular mechanisms remaining poorly understood. To address this gap, we determined when urethra closure occurs and identified gene expression patterns during the process of urethra closure in female neonatal mice from postnatal day (PND) 5 to 10. Using whole mount imaging and histology, we discovered that the initiation of urethra closure begins at PND7, and urethra closure is fully completed by PND10. To identify the genes associated with urethra closure, we conducted bulk RNA sequencing on female external genitalia prior to and after urethra closure. Gene ontology analyses revealed an increase in steroidogenic gene expression (Star, Hsd3b6, and Cyp17a1) during urethra closure, suggesting that the female genitalia locally produce steroids which could facilitate steroid signaling within the genitalia. With this study, we establish an anatomical timeline of female urethra closure and hypothesize a paracrine steroid signaling mechanism of urethra closure. These observations provide entry points to aid in further understanding external genital abnormalities, like hypospadias, in females.

Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial germ cells (PGCs) are the bipotential precursors of mature gametes that commit to an oogenic or spermatogenic fate in response to sex-determining cues from the fetal gonad. The critical processes required for PGCs to integrate and respond to signals from the somatic environment in gonads are not understood. In this study, we developed the first single-nucleus multiomics map of chromatin accessibility and gene expression during murine PGC development in both XX and XY embryos. Profiling of cell-type specific transcriptomes and regions of open chromatin from the same cell captured the molecular signatures and gene networks underlying PGC sex determination. Joint RNA and ATAC data for single PGCs resolved previously unreported PGC subpopulations and cataloged a multimodal reference atlas of differentiating PGC clusters. We discovered that regulatory element accessibility precedes gene expression during PGC development, suggesting that changes in chromatin accessibility may prime PGC lineage commitment prior to differentiation. Similarly, we found that sexual dimorphism in chromatin accessibility and gene expression increased temporally in PGCs. Combining single-nucleus sequencing data, we computationally mapped the cohort of transcription factors that regulate the expression of sexually dimorphic genes in PGCs. For example, the gene regulatory networks of XX PGCs are enriched for the transcription factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, and ZFX. Sex-specific enrichment of the forkhead-box and POU6 families of transcription factors was also observed in XY PGCs. Finally, we determined the temporal expression patterns of WNT, BMP, and RA signaling during PGC sex determination, and our discovery analyses identified potentially new cell communication pathways between supporting cells and PGCs. Our results illustrate the diversity of factors involved in programming PGCs towards a sex-specific fate., Competing Interests: Conflict of interest Statement (if requested by the journal) The authors declare no competing financial or non-financial interests.

The CTLA-4 and PD-1 checkpoints control immune responses and are key targets in immunotherapy. Both pathways are connected via a cis interaction between CD80 and PD-L1, the ligands for CTLA-4 and PD-1, respectively. This cis interaction prevents PD-1-PD-L1 binding but is reversed by CTLA-4 trans-endocytosis of CD80. However, how CTLA-4 selectively removes CD80, but not PD-L1, is unclear. Here, we show CTLA-4-CD80 interactions are unimpeded by PD-L1 and that CTLA-4 binding with CD80 does not displace PD-L1 per se. Rather, both rigidity and bivalency of CTLA-4 molecules are required to orientate CD80 such that PD-L1 interactions are no longer permissible. Moreover, soluble CTLA-4 released PD-L1 only at specific expression levels of CD80 and PD-L1, whereas CTLA-4 trans-endocytosis released PD-L1 in all conditions. These data show that PD-L1 release from CD80 is driven by orientation and bivalent cross-linking of membrane proteins and that trans-endocytosis of CD80 efficiently promotes PD-L1 availability., Competing Interests: Declaration of interests C.T.O., H.-C.C., C.L., and S.J.D. are full-time employees at and shareholders of AstraZeneca. M.A.R. and L.F. received funding from AstraZeneca in support of this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Testicular fetal Leydig cells are a specialized cell type responsible for embryo masculinization. Fetal Leydig cells produce androgens, that induce the differentiation of male reproductive system and sexual characteristics. Deficiencies in Leydig cell differentiation leads to various disorders of sex development and male reproductive defects such as ambiguous genitalia, hypospadias, cryptorchidism, and infertility. Fetal Leydig cells are thought to originate from proliferating progenitor cells in the testis interstitium, marked by genes like Arx , Pdgfra , Tcf21 and Wnt5a . However, the precise mechanisms governing the transition from interstitial cells to fetal Leydig cells remain elusive. Through integrated approaches involving mouse models and single-nucleus multiomic analyses, we discovered that fetal Leydig cells originate from a Nr2f2 -positive non-steroidogenic interstitial cell population. Embryonic deletion of Nr2f2 in mouse testes resulted in disorders of sex development, including dysgenic testes, Leydig cell hypoplasia, cryptorchidism, and hypospadias. We found that NR2F2 promotes the progenitor cell fate while suppresses Leydig cell differentiation by directly and indirectly controlling a cohort of transcription factors and downstream genes. Bioinformatic analyses of single-nucleus ATAC-seq and NR2F2 ChIP-seq data revealed putative transcription factors co-regulating the process of interstitial to Leydig cell differentiation. Collectively, our findings not only highlight the critical role of Nr2f2 in orchestrating the transition from interstitial cells to fetal Leydig cells, but also provide molecular insight into the disorders of sex development as a result of Nr2f2 mutations.

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer after hepatocellular carcinoma. Through data mining of publicly available iCCA transcriptomic datasets from the Gene Expression Omnibus, we identified SFN as the most significantly up-regulated gene in iCCA compared to normal tissue, focusing on the Gene Ontology term "cell proliferation" (GO:0008283). SFN encodes the 14-3-3σ protein, also known as stratifin, which plays crucial roles in various cellular processes., Materials and Methods: Immunohistochemistry was used to assess stratifin expression in 182 patients with localized iCCAs undergoing surgical resection. Patients were divided into low and high expression groups, and the association between stratifin expression and clinicopathological features was analyzed. Univariate and multivariate survival analyses were performed to assess overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS)., Results: Elevated stratifin expression in iCCAs was significantly associated with the absence of hepatitis, positive surgical margins, advanced primary tumor stages, and higher histological grades (all p ≤ 0.011). Survival analyses demonstrated a significant negative association between stratifin expression and all prognostic indicators, including OS, DSS, LRFS, and MeFS (all p ≤ 0.0004). Multivariate analysis revealed that stratifin overexpression was significantly correlated with poorer outcomes in terms of DSS, LRFS, and MeFS (all p < 0.001)., Conclusions: These findings suggest that stratifin may play a crucial role in iCCA oncogenesis and tumor progression, serving as a potential novel prognostic biomarker., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Oncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with premalignancy 1,2 . Achieving this phenotype typically requires a high level of oncogenic stress, yet the phenotype provoked by lower oncogenic dosage remains unclear. Here we develop oncogenic RAS dose-escalation models in vitro and in vivo, revealing a RAS dose-driven non-linear continuum of downstream phenotypes. In a hepatocyte OIS model in vivo, ectopic expression of NRAS(G12V) does not induce tumours, in part owing to OIS-driven immune clearance 3 . Single-cell RNA sequencing analyses reveal distinct hepatocyte clusters with typical OIS or progenitor-like features, corresponding to high and intermediate levels of NRAS(G12V), respectively. When titred down, NRAS(G12V)-expressing hepatocytes become immune resistant and develop tumours. Time-series monitoring at single-cell resolution identifies two distinct tumour types: early-onset aggressive undifferentiated and late-onset differentiated hepatocellular carcinoma. The molecular signature of each mouse tumour type is associated with different progenitor features and enriched in distinct human hepatocellular carcinoma subclasses. Our results define the oncogenic dosage-driven OIS spectrum, reconciling the senescence and tumour initiation phenotypes in early tumorigenesis., (© 2024. The Author(s).)

We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR). α-LGR5-ADC was the most effective modality for targeting LGR5 + cancer cells in vitro and demonstrated potent anti-tumour efficacy in a murine model of human NALM6 pre-B-ALL driving tumour attrition to less than 1% of control treatment. α-LGR5-BiTE treatment was less effective in the pre-B-ALL cancer model yet promoted a twofold reduction in tumour burden. α-LGR5-CAR-T cells also showed specific and potent LGR5 + cancer cell killing in vitro and effective tumour targeting with a fourfold decrease in pre-B-ALL tumour burden relative to controls. Taken together, we show that α-LGR5 can not only be used as a research tool and a biomarker but also provides a versatile building block for a highly effective immune therapeutic portfolio targeting a range of LGR5-expressing cancer cells., (© 2024. The Author(s).)

Aims: The probiotic bacterium Levilactobacillus brevis (L. brevis) has been proposed as a potential solution to manage mood disorders and alleviate stress-related sleep disturbances. However, the underlying mechanisms of its effects have not been fully elucidated. The aim of this study was to explore the impact and potential mechanisms of L. brevis SG031 supplementation on anxiety/depression-like behaviors and stress-induced changes in sleep patterns and sleep-related autonomic function., Main Methods: Male Wistar-Kyoto rats were administered low, medium, or high doses of L. brevis SG031 or a vehicle for 4 weeks, followed by behavioral tests to evaluate anxiety and depression. After an additional 2 weeks of SG031 or vehicle administration, a cage-exchange paradigm was performed with 24-hour physiological signal measurements under different stress conditions. Fecal samples were collected to construct a 16S rRNA library and assess fecal short-chain fatty acids (SCFAs)., Key Findings: High-dose SG031 administration yielded reduced depression-like responses and enhanced social interaction in behavioral tests. It also exhibited a protective effect against stress-induced sleep disturbance characterized by decreased sleep time, increased awake time, and autonomic dysfunction during sleep. Fecal examination indicated that high-dose SG031 administration exerted beneficial effects on gut health by maintaining the gut microbial abundance, preserving stability of the microbial composition, and enriching the gut with SCFAs, which were associated with improvements in sleep and autonomic function., Significance: These findings collectively underscore the multifaceted potential of SG031 in addressing mental health and stress-related sleep challenges through the modulation of the gut microbiota., Competing Interests: Declaration of competing interest We had a grant support (YM107C052) from Syngen Biotech Company. The company provided Levilactobacillus brevis SG031 (special screening and cultivation of strains) to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials., (© 2024. The Author(s).)

Aim: This study intended to validate the competency-based approach through an entrustable professional activity in the nursing undergraduate education arena in Taiwan., Background: Entrustable professional activity is a recommended strategy to enhance nursing competencies and skills. It has been widely applied to nursing education in Western countries, especially graduate programs. However, its effects in eastern countries and undergraduate programs remain unclear., Design: A quasi-experimental comparison design was used., Method: The study is conducted at the Department of Nursing at a university in southern Taiwan. A total of 72 Two-Year Nursing Program students participated in the study. After implementing the designated entrustable professional activity in the Wound Care Nursing course, outcomes were measured using the Competency Inventory of Nursing Students, Learning Satisfaction and Objective Structured Clinical Examinations. These outcomes were then compared with post-test results at the end of the semester. About 90 % of students completed the study with the test group (n=31) receiving extra activity and the comparison group (n=34) receiving usual teaching. Data were analyzed through chi-square, paired t and Student's t-test., Results: The test group demonstrated significantly higher scores in perceived competency and clinical examinations than the comparison group. However, both groups experienced an increase in learning satisfaction without reaching a significant difference., Conclusion: Results of the study indicate that competency-based pedagogy, e.g., using entrustable professional activities, should be integrated into nursing curricula to meet the new American Association of Colleges of Nursing standards with compelling evidence., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Left ventricular (LV) unloading prior to primary angioplasty in patients experiencing acute myocardial infarction holds promise for mitigating reperfusion injury and minimizing infarct size., Case Summary: This report delves into the utilization of left atrial venoarterial extracorporeal membrane oxygenation (LAVA-ECMO) as a pre-percutaneous transluminal coronary angioplasty (PTCA) intervention strategy aimed at augmenting circulatory support while unloading the LV. Three cases of patients with ST elevation myocardial infarction involving the left ascending coronary artery who underwent LAVA-ECMO before primary PTCA are presented. Each patient maintained robust LV systolic function following weaning from ECMO support., Discussion: These cases underscore the potential benefits of mechanical LV unloading prior to revascularization in reducing infarct size and mitigating the risk of post-myocardial infarction heart failure., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Engineering atomic-scale defects has become an important strategy for the future application of transition metal dichalcogenide (TMD) materials in next-generation electronic technologies. Thus, providing an atomic understanding of the electron-defect interactions and supporting defect engineering development to improve carrier transport is crucial to future TMDs technologies. In this work, we utilize low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/S) to elicit how distinct types of defects bring forth scattering potential engineering based on intervalley quantum quasiparticle interference (QPI) in TMDs. Furthermore, quantifying the energy-dependent phase variation of the QPI standing wave reveals the detailed electron-defect interaction between the substitution-induced scattering potential and the carrier transport mechanism. By exploring the intrinsic electronic behavior of atomic-level defects to further understand how defects affect carrier transport in low-dimensional semiconductors, we offer potential technological applications that may contribute to the future expansion of TMDs.

Background: We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole-exome sequencing revealed a de novo gain-of-function variant, p.Tyr715Cys, in the C-terminal domain of ClC-7 encoded by CLCN7., Methods: Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents., Results: The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC-7 antiporter activity in maintaining appropriate lysosomal pH., Conclusion: Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype-phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC-7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Reproductive processes are dynamic and involve extensive morphological remodeling and cell-cell interactions. Live imaging of organs enhances our understanding of how biological processes occur in real time. Slice culture is a type of organ culture where thick slices are collected from an organ and cultured for several days. Slice culture is a useful and easy-to-implement technique for live imaging of reproductive events at cellular resolution. Here we describe a pipeline of live imaging on slice culture to visualize the process of urethra closure in mouse embryonic penis as a proof of principle. In combination with genetic reporter mice, nuclear stains, and exposure experiments, we demonstrate the feasibility of slice culture on a reproductive organ. We also provide a step-by-step protocol and troubleshooting guide to facilitate the adoption of slice culture with live imaging in other reproductive organs. Lastly, we discuss potential utilities and experiments that could be implemented with slice culture in reproductive sciences., (Published by Oxford University Press on behalf of Society for the Study of Reproduction 2024.)

Background: Clinical reasoning is an essential nursing competency that students must develop to provide safe patient care. Developing and utilizing unfolding case studies, which present constantly changing patient conditions to improve students' clinical reasoning and to foster communication and self-reflection, can help to achieve that imperative., Objectives: To develop an unfolding case study and to test its effectiveness in improving clinical reasoning, team collaboration, and self-directed learning., Design: A mixed methods design., Setting: One university in Southern Taiwan., Participants: Forty nursing students., Methods: An unfolding case study was developed based on the clinical reasoning model and unfolding cases model. The Nurses Clinical Reasoning Scale, Self-Directed Learning Instrument, and Questionnaire of Group Responsibility and Cooperation in Learning Teams were used. Forty nursing students completed questionnaires and nine of them participated in focus group discussions. Wilcoxon signed-rank, Spearman correlation, regression, and inductive content analysis were used to analyze data., Results: Students' abilities in clinical reasoning, self-directed learning, and team collaboration were statistically significantly improved after implementation of the unfolding case study. Emergent themes included "patient-centered communication," "group inspiration and learning," "thinking critically and reflecting on oneself," and "applying theoretical knowledge in care to meet patients' changing needs.", Conclusions: Unfolding case studies provide a safe environment in which nursing students may learn and apply knowledge to safe patient care., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims and Objectives: To develop a Chinese version of a chronic wound health-related quality of life (QoL) instrument and to examine the psychometric properties of this instrument., Background: Existing QoL instruments are not tailored to the linguistic and cultural characteristics of Chinese-speaking patients; a version addressing this gap will increase clinical understanding of their healthcare experience and may help guide chronic wound care., Design: A methodological study., Methods: The method advanced by DeVellis (2017) was used to develop the instrument. An initial pool of 38 items was created. To optimize scale length and test reliability and validity, exploratory and confirmatory factor analyses were conducted. A total of 23 items formed the final pool. After two rounds of expert discussions, the average content validity index of the final 23 items was .89., Results: A total of 226 patients completed the instrument and were divided into two groups for further analysis. Exploratory factor analysis revealed that 15 items remained in four factors (social activity restrictions, physical and psychological disturbance, wound burden and daily life limitation), which accounted for 64.87% of the variance. Confirmatory factor analysis revealed an acceptable fit of the hypothesized factor structure and the convergent and discriminant validities were achieved. Cronbach's α coefficients for each factor were .807, .773, .799 and .713, respectively., Conclusion: The Chinese version of a chronic wound health-related QoL instrument consists of 15 items in four subscales and demonstrates good reliability and validity., Relevance to Clinical Practice: This instrument can be used intermittently or continuously to evaluate the treatment effect of chronic wounds by assessing health-related QoL. Scholars in Chinese-speaking regions may find this culturally compatible instrument useful when conducting studies related to chronic wounds., Patient or Public Contribution: Two hundred twenty-six participants provided their perspectives on health-related QoL., (© 2023 John Wiley & Sons Ltd.)

Sediments are important sinks for di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, and thus, maintaining the sediment quality is essential for eliminating plasticizers in aqueous environments and recovering the sediment ecological functions. To mitigate the potential risks of endocrine-disrupting compounds, identifying an effective and eco-friendly degradation process of organic pollutants from sediments is important. However, sustainable and efficient utilization of slow pyrolysis for converting shark fishbone to generate shark fishbone biochar (SFBC) has rarely been explored. Herein, SFBC biomass was firstly produced by externally incorporating heteroatoms or iron oxide onto its surface in conjunction with peroxymonosulfate (PMS) to promote DEHP degradation and explore the associated benthic bacterial community composition from the sediment in the water column using the Fe-N-SFBC/PMS system. SFBC was pyrolyzed at 300-900 °C in aqueous sediment using a carbon-advanced oxidation process (CAOP) system based on PMS. SFBC was rationally modified via N or Fe-N doping as a radical precursor in the presence of PMS (1 × 10 -5  M) for DEHP removal. The innovative SFBC/PMS, N-SFBC/PMS, and Fe-N-SFBC/PMS systems could remove 82%, 65%, and 90% of the DEHP at pH 3 in 60 min, respectively. The functionalized Fe 3 O 4 and heteroatom (N) co-doped SFBC composite catalysts within a hydroxyapatite-based structure demonstrated the efficient action of PMS compared to pristine SFBC, which was attributed to its synergistic behavior, generating reactive radicals (SO 4 •- , HO•, and O 2 •- ) and non-radicals ( 1 O 2 ) involved in DEHP decontamination. DEHP was significantly removed using the combined Fe-N-SFBC/PMS system, revealing that indigenous benthic microorganisms enhance their performance in DEHP-containing sediments. Further, DEHP-induced perturbation was particularly related to the Proteobacteria phylum, whereas Sulfurovum genus and Sulfurovum lithotrophicum species were observed. This study presents a sustainable method for practical, green marine sediment remediation via PMS-CAOP-induced processes using a novel Fe-N-SFBC composite material and biodegradation synergy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: To assess the quality change of our single-center pediatric colonoscopy after applying bundle for bowel preparation and general anesthesia and centralize the procedure using terminal ileum (TI) intubation rate as the main indicator., Methods: All elective colonoscopies performed for patients younger than 18 years old in MacKay Memorial Hospital from July 2015 through June 2020 (assigned to group 1, before bundle) and from August 2020 through July 2021 (assigned to group 2, after bundle) were retrospectively reviewed for demographic characteristics, indications, bowel preparation agent and cleansing level, diagnostic and therapeutic procedures, maximum intestinal level reached, and cecal intubation and total procedure time. Statistical analysis was done using P value < 0.05 considered to be significant., Results: Analysis included 45 and 32 colonoscopies in group 1 and 2, respectively. Bloody stool was the most frequent indication in both groups. Both TI intubation rate (42.2 % vs. 75.0 %, P = 0.004) and biopsy rate (45.0 % vs. 75.9 %, P = 0.01) increased significantly from group 1 to group 2. The narrower standard deviation of bowel preparation score (1.93 vs. 1.15) and total procedure time (37.71 vs. 22.29) in group 2 indicated a more stable quality, although the mean showed no difference. There was no statistical difference in age, gender, body weight, cecal intubation rate, or cecal intubation time., Conclusion: A higher TI intubation rate and biopsy rate indicated an improved quality of pediatric colonoscopy after applying bundle including bowel preparation and general anesthesia, with additional centralization., Competing Interests: Conflict of Interest Statement The authors have no conflicts of interest to declare., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Purpose: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50-80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia., Methods: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia., Results: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01-0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05-0.31), and propofol administration (OR = 0.30, 95%CIs 0.10-0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied., Conclusions: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted., Trial Registration: PROSPERO CRD42021285200., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

The diagnosis of lymphoma is based on histopathological and immunophenotypical features. CD5 and CD10 are traditionally considered a T-cell antigen and a germinal center B-cell antigen, respectively. It is very unusual for a low-grade B-cell lymphoma (BCL) to co-express CD5 and CD10. Although the biologic basis or clinical significance of such co-expression is unclear, this rare event may pose a significant diagnostic challenge. Here, we report a case of a 63-year-old male presenting with bilateral cervical lymphadenopathy and lymphocytosis. Histologically, the nodal tumor was largely diffuse with neoplastic small atypical lymphocytes co-expressing CD5, CD10, and CD20, but not CD23 or cyclin D1. The leukemic cells in the peripheral blood exhibited hairy projections. Taking together the marked splenomegaly, involvement of lymph nodes, bone marrow, and peripheral blood, a final diagnosis of splenic marginal zone lymphoma (SMZL) was reached. The patient was alive with partial response for 10 months after immunochemotherapy. The dual expression of CD5 and CD10 is extremely unusual for low-grade BCL and may lead to an erroneous diagnosis. Integrating the findings into peripheral blood smear tests, flow cytometry, histopathology, imaging, and clinical features is mandatory to exclude other lymphoma types and to reach a correct diagnosis, particularly for a case with nodal presentation.

Polycyclic aromatic hydrocarbons (PAHs) are critical environmental concerns due to their intrinsic toxic aromatic nature and concomitant circumstances that potentially harm the ecological and human health. In this study, converting mahogany (Swietenia macrophylla King) pericarps to value-added biochar by pyrolysis for evaluating the potential formation/destruction of biochar-bound PAHs was studied for the first time. This study designed and optimized the thermal processing conditions at 300-900 °C in the CO 2 or N 2 atmosphere, and heteroatoms (N, O, B, NB, and NS) were modified for mahogany pericarps biochar (MPBC) production. The MPBC500 exhibited significantly higher pyrolysis products of PAHs (2780 ± 38 ng g -1 ) than that of MPBC900 (78 ± 6 ng g -1 ) under N 2 without introducing modified elements. Specifically, the inhibition capacity of MPBC500 for PAHs under CO 2 was improved most efficiently by the active nitrogen species of the pyridinic N and pyrrolic N groups. The pyrolysis conditions and heteroatom modification of MPBC altered its physicochemical properties, that is, aromaticity and hydrophobicity, affecting the PAH concentration and composition in the pyrolysis products. This study reveals sustainable approaches to reduce the environmental footprint of biochar by focusing on increases in PAHs pollution in sustainable biochar produced from a low-carbon bioeconomy perspective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Summary: The crescentic alar groove serves as a topographic landmark that frames the ala and separates this convex structure from the surrounding cosmetic subunits. This aesthetic landmark can be attenuated or even obliterated during wound repair in this area. Flaps spanning the alar crease are often noticeably bulky with a pin-cushioned appearance in nasal reconstruction, and it is challenging to reproduce a natural-appearing alar groove. The authors proposed a novel technique with a modified, interrupted inverted horizontal mattress suture to create an alar groove. From March of 2016 to May of 2021, 22 consecutive patients with alar defects who underwent nasal reconstruction with the paramedian forehead flap were identified. All patients underwent the authors' novel technique for the creation of the alar groove. The mean follow-up time was 3 years 7 months (range, 14 months to 5 years). A total of 32 alar crease creation suture operations were performed. All uneven wounds healed uneventfully within 2 weeks. Two cases of postoperative fading alar grooves required alar crease creation sutures to be redone. The authors' novel alar crease creation suture is a safe, straightforward, and reliable technique to create an aesthetic alar groove in forehead flap nasal reconstruction. It can create a medially shallow and laterally deep alar crease without apparent complications., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Biochar production from cellulose biomass is an alternative solution in the search for clean and renewable biofuel. However, the rational design of cellulose biochar (CLBC) for polycyclic aromatic hydrocarbons (PAHs) reduction by integrating pyrolysis process parameters and introducing heteroatoms as inhibitors remains to be studied. Therefore, exogenous heteroatoms (N, B, S, SB, NB, and NS) were used to modify CLBC for the first time. CLBC300 pyrolyzed at 300 °C in a CO 2 atmosphere achieved the highest concentrations of PAHs (4982 ± 271 ng g -1 ), compared with that of CLBC700 (3615 ± 71 ng g -1 ) formed in a N 2 atmosphere without heteroatom doping. The results showed that binary nitrogen- and sulfur-doped CLBC exhibited remarkable PAH-removal performance of 99 % with the lowest toxic equivalency (TEQ) value of 9 ng g -1 . Overall, this study presents novel insights into the development of a heteroatom-based modification approach for reducing CLBC-borne PAHs and creating value-added products from cellulose biomass., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The programming of innate and adaptive immunity plays a pivotal role in determining the course of pregnancy, leading to either normal term birth (TB) or preterm birth (PB) through the modulation of macrophage (M1/M2) differentiation. Extracellular vesicles (EVs) in maternal blood, harboring a repertoire of physiological and pathological messengers, are integral players in pregnancy outcomes. It is unknown whether urinary EVs (UEVs) could serve as a non-invasive mechanistic biomarker for predicting PB. Methods: This study investigated first-trimester UEVs carrying M1 messengers with altered immune programming, aiming to discern their correlation to subsequent PB. A birth cohort comprising 501 pregnant women, with 40 women experiencing PB matched to 40 women experiencing TB on the same day, was examined. First-trimester UEVs were isolated for the quantification of immune mediators. Additionally, we evaluated the UEV modulation of "trained immunity" on macrophage and lymphocyte differentiations, including mRNA expression profiles, and chromatin activation modification at histone 3 lysine 4 trimethylation (H3K4me3). Results: We found a significant elevation ( p < 0.05) in the particles of UEVs bearing characteristic exosome markers (CD9/CD63/CD81/syntenin) during the first trimester of pregnancy compared to non-pregnant samples. Furthermore, UEVs from PB demonstrated significantly heightened levels of MCP-1 ( p = 0.003), IL-6 ( p = 0.041), IL-17A ( p = 0.007), IP-10 ( p = 0.036), TNFα ( p = 0.004), IL-12 ( p = 0.045), and IFNγ ( p = 0.030) relative to those from TB, indicative of altered M1 and Th17 differentiation. Notably, MCP-1 (>174 pg/mL) exhibited a sensitivity of 71.9% and specificity of 64.6%, and MCP-1 (>174 pg/mL) and IFNγ (>8.7 pg/mL) provided a higher sensitivity (84.6%) of predicting PB and moderate specificity of 66.7%. Subsequent investigations showed that UEVs from TB exerted a significant suppression of M1 differentiation (iNOS expression) and Th17 differentiation (RORrT expression) compared to those of PB. Conversely, UEVs derived from PB induced a significantly higher expression of chromatin modification at H3K4me3 with higher production of IL-8 and TNFα cytokines ( p < 0.001). Implications: This pioneering study provides critical evidence for the early detection of altered M1 and Th17 responses within UEVs as a predictor of PB and early modulation of altered M1 and Th17 polarization associated with better T-cell regulatory differentiation as a potential prevention of subsequent PB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Lin, Tseng, Chien, Lee and Yang.)

This research was to study the efficiency of Sphagnum moss-derived biochar (SMBC) in removing polycyclic aromatic hydrocarbons (PAHs) from marine sediment using a peroxymonosulfate (PMS)-based carbon-advanced oxidation process (PMS-CAOPs). Sphagnum moss-derived biochar (SMBC) was generated via a simple thermochemical process for PMS activation toward enhancing decontamination of sediments. At pH 6, the SMBC/PMS system achieved a PAH removal efficiency exceeding 78% in 12 h reaction time. Moreover, PAHs of 6-, 5-, 4-, 3-, and 2-ring structures exhibited 98%, 74%, 68%, 85%, and 91%, of removal, respectively. The SMBC activation of PMS generated both radicals (SO 4 •- and HO•) and nonradical ( 1 O 2 ), species responsible for PAHs degradation, attributed primarily to inherent iron and carbon moieties. The significant PAHs degradation efficiency showcased by the SMBC/PMS process holds promise for augmenting the performance of indigenous benthic microbial activity in sediment treatment contexts. The response of sediment microbial communities to PAH-induced stress was particularly associated with the Proteobacteria phylum, specifically the Sulfurovum genus. The findings of the present study highlight the efficacy of environmentally benign reactive radical/nonradical-based PMS-CAOP using pristine carbon materials, offering a sustainable strategy for sediment treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release.

Background: Probiotic supplementation is increasingly being given to very low birth weight (VLBW) preterm infants. This preliminary observational study aimed to investigate the effects of multiple-strain probiotics on the gut microbiota of VLBW preterm infants., Methods: We collected meconium and stool samples on days 14, 30, and 60 after birth from 49 VLBW infants with a gestational age of <32 weeks. The infants were divided into the probiotics (n = 24) and control (n = 25) groups. The microbial composition and diversity in the gut of the two groups were analyzed using 16 S rRNA gene sequencing., Results: The relative abundance of Bifidobacterium and Lactobacillus was significantly higher in the probiotics group than in the control group on days 14, 30, and 60 (Bifidobacterium: p = 0.002, p < 0.0001, and p < 0.0001, respectively; Lactobacillus: p = 0.012, p < 0.0001, and p < 0.0001, respectively). The control group exhibited a significantly higher proportion of participants with a low abundance (<1%) of Bifidobacterium or Lactobacillus on days 14, 30, and 60 than those in the probiotic group. Moreover, the probiotics group exhibited a significantly lower abundance of Klebsiella on days 14 and 30 (2.4% vs. 11.6%, p = 0.037; and 7.9% vs. 16.6%, p = 0.032, respectively) and of Escherichia-Shigella on day 60 than the control group (6.1% vs. 12.3%, p = 0.013). Beta diversity analysis revealed that the microbiota profile was clearly divided into two groups on days 30 and 60 (p = 0.001)., Conclusion: Probiotic supplementation significantly increased the relative abundance of Bifidobacterium and Lactobacillus and inhibited the growth of potential pathogens. Furthermore, probiotic supplementation led to a distinct gut microbiota profile. Further research is needed to identify probiotic strains that exert significant influence on the gut microbiome and their long-term health implications in preterm infants., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

This study investigates the mechanism behind the oxidation di-(2-ethylhexyl) phthalate (DEHP) in marine sediment by coupling sulfite using biochar prepared from sorghum distillery residue (SDRBC). The rationale for this investigation stems from the need to seek effective methods for DEHP-laden marine sediment remediation. The aim is to assess the feasibility of sulfite-based advanced oxidation processes for treating hazardous materials such as DEHP containing sediment. To this end, the sediment in question was treated with 2.5 × 10 -5  M of sulfite and 1.7 g L -1 of SDRBC700 at acidic pH. Additionally, the study demonstrated that the combination of SDRBC/sulfite with a bacterial system enhances DEHP removal. Thermostilla bacteria were enriched, highlighting their role in sediment treatment. This study concludes that sulfite-associated sulfate radicals-driven carbon advanced oxidation process (SR-CAOP) offers sustainable sediment pretreatment through the SDRBC/sulfite-mediated microbial consortium, in which the SO 3 •- and 1 O 2 were responsible for DEHP degradation. SDRBC/sulfite offers an effective and environmentally friendly method for removing DEHP. Further, these results can be targeted at addressing industry problems related to sediment treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To investigate caregivers' perceptions of using a ride-on car (ROC) and observe behavioral changes in their children following ROC training and conventional therapy., Methods: The study included 37 toddlers with motor delays and their caregivers, divided into an ROC training group (27 participants) and a conventional therapy group (10 participants). A binary, multiple-choice, and open-ended questionnaire was administered before and after a 3-month intervention period., Results: Over 70% of caregivers had no experience using mobility devices before the intervention. Before the intervention, children's ability and age were key barriers to using mobility devices. After the intervention, caregivers in the ROC group were more inclined than those in the control group to allocate a larger budget for these devices., Conclusions: The findings highlight the importance of pediatric physical and occupational therapists working collaboratively with caregivers during such interventions and raising awareness about government subsidies and resources available for mobility devices., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Background: Narrative medicine can serve as a tool to empathize with human beings' predicament and suffering. The research intended to examine whether the use of narrative medicine to form an empathetic connection could bring any positive impacts on health professions students., Methods: A two-group quasi-experimental design was adopted to examine whether the intervention of narrative medicine to form an empathetic connection could demonstrate differences between the experimental group (35 students) and the control group (32 students) with regard to professional identity, self-reflection, emotional catharsis, and reflective writing competency. These 67 participants were health professions students in a medical university (mean age = 20.02; SD  = 0.23), with varied majors in health disciplines. The 16-week intervention was the use of narrative medicine to form an empathetic connection with those suffering, via the three stages of narrative medicine: attention → representation → affiliation. The quantitative instruments included a professional identity scale (PIS-HSP), a reflective thinking scale (RTS-HSP), and an emotional catharsis scale (ECS-IN), as well as an analytic reflective writing scoring rubric (ARWSR-HSP). To triangulate the quantitative results, the study also used the student interviews. The SPSS software was used to analyze the data., Results: The quantitative results demonstrated that the narrative medicine-based intervention could bring positive effects on the health professions students. After going through the intervention, the students in the experimental group had stronger professional identity, a higher reflective thinking level, more emotional catharsis, and greater improvement in reflective writing competency than those not receiving the intervention, though some subscales not reaching statistical significance., Conclusion: This research results proved that the use of narrative medicine to form an empathetic connection could bring positive impacts on health professions students regarding professional identity, self-reflection, emotional catharsis, and self-reflective writing competency.

Background: Although medical literature has highlighted the importance of role modelling, hardly any reveals how humanistic qualities and role modelling should be taught. This study aimed to determine whether the use of Bandura's social cognitive learning for humanistic professional role modelling could elicit any positive effect on medical university students' awareness of humanistic professionalism, caring behaviours, and school-to-work transitional anxiety., Methods: We conducted a 16-week quasi-experimental study to examine whether the intervention could elicit any differences between the experimental group (BanduraSCLT - HPRM - Literature-and-Film Study; N  = 34) and the control group (non-BanduraSCLT - HPRM - Literature-and-Film Study; N  = 33), comprising of medical university students from the central part of Taiwan. The quantitative instruments included the Humanistic Professional Awareness Scale (HPAS-HSP), Caring Behaviour Scale (CBS-HSP) and School-to-Work Transitional Anxiety Scale (StWTA-HS). One-way MANOVA (multivariate analysis of variance) and one-way MANCOVA (multivariate analysis of covariance) were used for statistical analysis., Results: The results revealed that students who received Bandura's social cognitive learning for humanistic professional role modelling had significantly stronger humanistic professional awareness in terms of 'personal integrity and accountability', 'sensitivity to others' and 'professional competence'. They also had more effective caring behaviour in terms of 'support and attentiveness', 'professional knowledge and skills', 'gratifying needs and responsiveness' and 'confidentiality and trust'. In addition, they had less school-to-work transitional anxiety in terms of 'inexperience in professional knowledge and skills', 'fear of death', 'fear of being infected' and 'interpersonal interactions.', Conclusion: The findings suggest that using Bandura's social cognitive learning for humanistic professional role modelling can have a positive impact on awareness of humanistic professionalism, caring behaviour and school-to-work transitional anxiety. Hence, it can be an effective teaching tool for medical education.

The determination of resection extent traditionally relies on the microscopic invasiveness of frozen sections (FSs) and is crucial for surgery of early lung cancer with preoperatively unknown histology. While previous research has shown the value of optical coherence tomography (OCT) for instant lung cancer diagnosis, tumor grading through OCT remains challenging. Therefore, this study proposes an interactive human-machine interface (HMI) that integrates a mobile OCT system, deep learning algorithms, and attention mechanisms. The system is designed to mark the lesion's location on the image smartly and perform tumor grading in real time, potentially facilitating clinical decision making. Twelve patients with a preoperatively unknown tumor but a final diagnosis of adenocarcinoma underwent thoracoscopic resection, and the artificial intelligence (AI)-designed system mentioned above was used to measure fresh specimens. Results were compared to FSs benchmarked on permanent pathologic reports. Current results show better differentiating power among minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and normal tissue, with an overall accuracy of 84.9%, compared to 20% for FSs. Additionally, the sensitivity and specificity, the sensitivity and specificity were 89% and 82.7% for MIA and 94% and 80.6% for IA, respectively. The results suggest that this AI system can potentially produce rapid and efficient diagnoses and ultimately improve patient outcomes.

Background: The arteriovenous fistula is the preferred access route for hemodialysis, although its high primary failure rate remains a clinical challenge. Multiple studies have attempted to determine the risk factors for primary arteriovenous fistula failure; however, none have identified pulse pressure as a potential predictive marker. High pulse pressure is a surrogate poor arterial compliance endpoint and leads to inferior cardiovascular outcomes. Our aim was to determine whether elevated pulse pressure indicates poor arteriovenous fistula maturation., Methods: We retrospectively reviewed 274 patients who underwent an arteriovenous fistula index operation between September 1, 2018 and May 31, 2019. Demographic, clinical data, and operative parameters were collected and analyzed. The maximum follow-up period was 365 days. Arteriovenous fistula failure was defined as the inability to achieve functional use during the follow-up period. We identified risk factors for arteriovenous fistula failure by performing a multivariate logistic regression analysis using backward elimination procedures., Results: A total of 274 patients were included in the study. The patients' average age was 61.3 ± 14.0 years, approximately half of the patients ( n  = 161, 58.8%) were male, and the majority had hypertension. At the end of the follow-up period, 68 (24.8%) had arteriovenous fistula failure. The proportion of patients with pulse pressure values of >60 mmHg was significantly higher in the failure group than in the maturation group (66.0% vs 80.9%; p  = 0.021). A PP value of >60 mmHg (odds ratio = 2.25; 95% confidence interval = 1.14-4.42; p  = 0.019) and coronary artery disease or myocardial infarction (odds ratio = 1.97; 95% confidence interval = 1.01-3.84; p  = 0.045) were found to be independent risk factors for primary arteriovenous fistula failure., Conclusions: High pulse pressure is an independent risk factor for primary arteriovenous fistula failure., 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.

Background: The coronavirus disease pandemic has had a tangible impact on bronchoscopy for burn inpatients due to isolation and triage measures. We utilised the machine-learning approach to identify risk factors for predicting mild and severe inhalation injury and whether patients with burns experienced inhalation injury. We also examined the ability of two dichotomous models to predict clinical outcomes including mortality, pneumonia, and duration of hospitalisation., Methods: A retrospective 14-year single-centre dataset of 341 intubated patients with burns with suspected inhalation injury was established. The medical data on day one of admission and bronchoscopy-diagnosed inhalation injury grade were compiled using a gradient boosting-based machine-learning algorithm to create two prediction models: model 1, mild vs. severe inhalation injury; and model 2, no inhalation injury vs. inhalation injury., Results: The area under the curve (AUC) for model 1 was 0·883, indicating excellent discrimination. The AUC for model 2 was 0·862, indicating acceptable discrimination. In model 1, the incidence of pneumonia (P < 0·001) and mortality rate (P < 0·001), but not duration of hospitalisation (P = 0·1052), were significantly higher in patients with severe inhalation injury. In model 2, the incidence of pneumonia (P < 0·001), mortality (P < 0·001), and duration of hospitalisation (P = 0·021) were significantly higher in patients with inhalation injury., Conclusions: We developed the first machine-learning tool for differentiating between mild and severe inhalation injury, and the absence/presence of inhalation injury in patients with burns, which is helpful when bronchoscopy is not available immediately. The dichotomous classification predicted by both models was associated with the clinical outcomes., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P < 0.001), large duct type (P=0.024) and poor histological grade (P = 0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P = 0.0025), local recurrence-free (P < 0.0001) and metastasis-free survival (P < 0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P = 0.034], disease-specific (HR 2.011; P = 0.039), local recurrence-free (HR 2.721; P < 0.001) and metastasis-free survival (HR 3.117; P < 0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-βsignaling pathway' and 'platelet-derived growth factor receptor-β signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ong et al.)

Objective: Viewing that there is a lack of valid and reliable measures to assess visual literacy in clinical and healthcare settings, this study aimed to develop a visual literacy scale to assess health students' and professionals' visual literacy, by which teachers can further help them sharpen their visual literacy skills and sensitivity to let them reach effective communication in clinical and healthcare settings., Methods: The scale was constructed according to Slavec and Drnovšek's three-phase scale development process: theoretical significance and existence of the scale construct, representative data collection and appropriate data collection methods, and statistical analysis of data collection and statistical evidence of the scale construct. To investigate the psychometrical properties, the researchers first performed a pilot study on randomly selected 464 health students and professionals, using exploratory factor analysis (EFA) with SPSS to derive the hidden factor structure, and then on randomly selected 303 participants, using confirmatory factor analysis (CFA) with AMOS to validate the derived factor structure. Internal consistency, convergent validities, discriminant validities, and goodness-of-fit indices were also examined in the study., Results: After going through the EFA, 30 items in three factors were identified: "allegorical meaning" (12 items), "explicit meaning" (10 items), and "symbolic meaning" (8 items). The three factors explained 73.191 of the total variance. The CFA generated the same three factors and 22 items: "allegorical meaning" (12 items), "explicit meaning" (4 items), and "symbolic meaning" (6 items). The three factors accounted for 75.022% of variance. Both the EFA and CFA models demonstrated satisfactory goodness-of-fit and good convergent and discriminant validities. Regarding the reliabilities, the Cronbach's alpha values in the EFA and CFA models were all above 0.90., Conclusion: The findings have demonstrated that the VLS-HSP can be a formal instrument to measure visual literacy on health students and professionals., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Wang and Liao.)

Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p < 0.001), large duct type (p = 0.004), and poorly differentiated histology (p = 0.002). COMP overexpression correlates with poorer DFS (HR, 3.651; p = 0.001), OS (HR, 1.827; p = 0.023), LRFS (HR, 4.077; p < 0.001), and MFS (HR, 3.718; p < 0.001). High COMP expression ties to worse overall survival (p = 0.0001), DSS (p < 0.0001), LRFS (p < 0.0001), and MFS (p < 0.0001). In conclusion, COMP overexpression links to poor prognosis and pathological features in iCCA, indicating its potential as a biomarker., (© 2023. Springer Nature Limited.)

Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear. Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group ( n = 15,697) and an unvaccinated group ( n = 21,325). Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47-0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60-0.95; aHR: 0.66, 95% CI: 0.53-0.82; aHR: 0.26, 95% CI: 0.19-0.36, after receiving 1, 2-3 and ≥4 vaccinations, respectively). Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Jong, Zheng, Zheng, Lin, Chiu, Hsu, Fang, Hao, Chen, Yang, Lee and Liu.)

Background: Traditionally, radial forearm free flaps are utilized for nasal lining reconstruction when local flaps cannot provide adequate coverage. However, according to our clinical observation, the skin of the forearm flap is relatively thin and prone to collapse. We present a series of nasal reconstructions using free flaps harvested from the lower extremities to determine if the thick flap could provide more support and decrease the tendency of airway collapse., Methods: From March 2011 to July 2021, we identified 15 patients who underwent total or subtotal nasal reconstruction with free flap from the lower extremities (10 anterolateral thigh flap, 4 medial sural artery perforator flap, and 1 profunda artery perforator flap). We included 15 patients who underwent free forearm flap reconstruction as controls. The Nasal Obstruction Symptoms Evaluation (NOSE) score was utilized to subjectively evaluate the degree of nasal obstruction symptoms., Results: The lower extremity group had a lower NOSE score than the forearm group (25.4 vs. 40). It took more time (6.5 vs. 4.2 months) and more surgeries (4.6 vs. 2.6) from the first free flap reconstruction till forehead flap reconstruction in the lower extremity group than in the forearm group, although the total number of surgeries was comparable between the 2 groups (7.2 vs. 8.1)., Conclusions: Utilizing free flaps from the lower extremities in total or subtotal reconstruction of the nasal lining may decrease the tendency of flap collapse and alleviate airway obstruction symptoms and may also allow reconstruction of surrounding defects simultaneously compared with using forearm flaps., Competing Interests: Conflict of Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: The ability to simultaneously cut and perform hemostasis with low lateral thermal injury makes carbon dioxide laser a useful tool in blepharoplasty. Monopolar electrosurgery is another commonly used cutting tool that improves the quality of hemostasis and cutting speed. This study aimed to objectively and quantitatively assess the intraoperative and postoperative outcomes of transconjunctival lower blepharoplasty using either a carbon dioxide laser or monopolar electrosurgery., Methods: Between August of 2018 and March of 2021, 78 patients who underwent transconjunctival lower blepharoplasty were assigned randomly to the carbon dioxide laser group or the monopolar electrosurgery group. Patient-related parameters were recorded. Periorbital bruises were assessed objectively and quantitatively using the ecchymosis evaluation score. Analyses were performed using the independent sample t test, the Mann-Whitney U test, the chi-square test, and the Fisher exact test., Results: Sex, age, local anesthesia injection volume, and fat removal volume were not different between the groups. Patients' subjective intraoperative heat sensation was significantly higher in the monopolar electrosurgery group than in the carbon dioxide laser group. The carbon dioxide laser group had a significantly lower incidence of postoperative chemosis than the monopolar electrosurgery group. All patients had uncomplicated wound healing, except three (7.89%) patients in the monopolar electrosurgery group who developed conjunctival granuloma. Operation time, intraoperative pain sensation, intraoperative blood pressure, postoperative ecchymosis, conjunctivitis, and patients' aesthetic satisfaction did not differ between the groups., Conclusion: The authors' findings revealed that carbon dioxide laser is a useful technique for reducing intraoperative heat sensation and postoperative chemosis and may prevent conjunctival wound complications., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Elevated triglyceride glucose (TyG) index is associated with an increased risk of cardiovascular disease. The current study aimed to investigate whether the TyG index was correlated with renal function decline in patients with hypertension. Han Chinese participants with essential hypertension were included. The TyG index was calculated as ln[fasting triglycerides (mg/dL) * fasting glucose (mg/dL)/2]. Renal function decline was defined as >25% decline in estimated glomerular filtration rate (eGFR). The Cox proportional hazard regression model was used to examine the independent effect of the TyG index on renal events. In total, 548 Han Chinese hypertensive participants with a mean age of 62.1 ± 14.3 years were eligible for enrollment. During a mean follow-up period of 4.7 ± 3.1 years, 97 patients suffered from >25% decline in eGFR. When compared to those without eGFR decline, patients with eGFR decline had higher fasting triglyceride levels (P = .056), fasting glucose levels (P = .014), and TyG indexes (P = .014). The Cox proportional hazard regression model revealed that the TyG index (hazard ratio [HR] = 1.490; 95% confidence interval [CI] = 1.016-2.185, P = .041), office systolic blood pressure (HR = 1.013; 95% CI = 1.000-1.026, P = .047), diabetes mellitus (HR = 1.797, 95% CI = 1.026-3.147, P = .040), and baseline eGFR (HR = 1.015; 95% CI = 1.002-1.028, P = .025) were associated with renal events. In conclusions, an elevated TyG index is independently associated with an increased risk of eGFR decline in hypertensive patients., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The formation of 2- to 6-ring polycyclic aromatic hydrocarbons (PAHs) in sorghum distillery residue-derived biochar (SDRBC) was evaluated under different thermochemical pyrolysis conditions of carbonization atmosphere (N 2 or CO 2 ), temperature (300-900 °C) and doping with nonmetallic elements, i.e., N, B, O, P, N + B, and N + S. The results indicated that without surface modification, PAHs formation was 944 ± 74 ng g -1 , the highest level, and 181 ± 16 ng g -1 , the lowest level, at 300 °C in N 2 and CO 2 atmosphere, respectively. Boron doping of SDRBC significantly reduced the PAHs content (by 97%) under N 2 at 300 °C. Results demonstrated that boron modified SDRBC exhibited the highest degree of PAHs reduction. Combined pyrolysis temperature and atmosphere in addition to heteroatom doping is a robust and viable strategy for efficient suppression of PAHs formation and high-value utilization of pyrolysis products of low carbon footprint., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)