Ctr9 promotes virulence of Candida albicans by regulating methionine metabolism.

Candida albicans, a part of normal flora, is an opportunistic fungal pathogen and causes severe health issues in immunocompromised patients. Its pathogenicity is intricately linked to the transcriptional regulation of its metabolic pathways. Paf1 complex (Paf1C) is a crucial transcriptional regulator that is highly conserved in eukaryotes. The objective of this study was to explore the role of Paf1C in the metabolic pathways and how it influences the pathogenicity of C. albicans. Paf1C knockout mutant strains of C. albicans (ctr9Δ/Δ, leo1Δ/Δ, and cdc73Δ/Δ) were generated using the CRISPR-Cas9 system. To investigate the effect of Paf1C on pathogenicity, macrophage interaction assays and mouse survival tests were conducted. The growth patterns of the Paf1C knockout mutants were analyzed through spotting assays and growth curve measurements. Transcriptome analysis was conducted under yeast conditions (30°C without serum) and hyphal conditions (37°C with 10% FBS), to further elucidate the role of Paf1C in the pathogenicity of C. albicans. CTR9 deletion resulted in the attenuation of C. albicans virulence, in macrophage and mouse models. Furthermore, we confirmed that the reduced virulence of the ctr9Δ/Δ mutant can be attributed to a decrease in C. albicans cell abundance. Moreover, transcriptome analysis revealed that metabolic processes required for cell proliferation are impaired in ctr9Δ/Δ mutant. Notably, CTR9 deletion led to the downregulation of methionine biosynthetic genes and the cAMP-PKA signaling pathway-related hypha essential genes, which are pivotal for virulence. Our results suggest that Ctr9-regulated methionine metabolism is a crucial factor for determining C. albicans pathogenicity.

Enhanced Osteogenesis in 2D and 3D Culture Systems Using RGD Peptide and α-TCP Phase Transition within Alginate-Based Hydrogel.

Cell-laden hydrogels have been extensively investigated in various tissue engineering fields by their potential capacity to deposit numerous types of cells in a specific area. They are largely used in soft-tissue engineering applications because of their low mechanical strength. In addition, sodium alginate is well-known for its encapsulation, loading capacity and for being easily controllable; however, it lacks cell-binding ligands and hence the ability to adhere cells. In this study, it is aimed to enhance osteogenesis in cells encapsulated in alginate and improve its mechanical properties by introducing a synthetic peptide and calcium phosphate phase transition. To increase cell-hydrogel interactions and increasing cell viability, an RGD peptide is added to a photocrosslinkable methacrylate-modified alginate, and alpha-tricalcium phosphate (α-TCP) is added to the hydrogel to increase its mechanical strength via phase transition. Cell proliferation, growth, and differentiation are assessed in both 2D and 3D cell cultures. The addition of α-TCP significantly improved the mechanical properties of the hydrogel. Moreover, the RGD peptide and α-TCP showed a synergistic effect with significantly improved cell adhesion and osteogenesis in both 2D and 3D cell cultures. Therefore, the functional hydrogel developed in this study can potentially be used for bone tissue regeneration.

Paramixta manurensis gen. nov., sp. nov., a novel member of the family Erwiniaceae producing indole-3-acetic acid isolated from mushroom compost.

There are numerous species in the Erwiniaceae family that are important for agricultural and clinical purposes. Here we described the Erwiniaceae bacterium PD-1 isolated from mushroom (Pleurotus eryngii) compost. Comparative genomic and phylogenetic analyses showed that the strain PD-1 was assigned to a new genus and species, Paramixta manurensis gen. nov., sp. nov. in the family Erwiniaceae. From the average amino acid index, we identified the five AroBEKAC proteins in the shikimate pathway as a minimal set of molecular markers to reconstruct the phylogenetic tree of the Erwiniaceae species. The strain PD-1 containing annotated genes for ubiquinone and menaquinone produced a higher level of ubiquinone (Q8) than demethylmenaquinone (DMK8) and menaquinone (MK8) in anaerobic condition compared to aerobic condition, as similarly did the reference strains from the genera Mixta and Erwinia. Results from fatty acid methyl ester and numerical analyses of strain PD-1 showed a similarity to species of the genera Mixta and Winslowiella. This study revealed that the strain's ability to utilize polyols, such as glycerol, erythritol, and D-arabitol, distinguished the strain PD-1 from the nearest relative and other type strains. The analyzed genetic markers and biochemical properties of the strain PD-1 suggest its potential role in the process of mushroom compost through the degradation of carbohydrates and polysaccharides derived from fungi and plants. Additionally, it can produce a high concentration of indole-3-acetic acid as a plant growth-promoting agent.

Surface Crystal and Degradability of Shape Memory Scaffold Essentialize Osteochondral Regeneration.

The minimally invasive deployment of scaffolds is a key safety factor for the regeneration of cartilage and bone defects. Osteogenesis relies primarily on cell-matrix interactions, whereas chondrogenesis relies on cell-cell aggregation. Bone matrix expansion requires osteoconductive scaffold degradation. However, chondrogenic cell aggregation is promoted on the repellent scaffold surface, and minimal scaffold degradation supports the avascular nature of cartilage regeneration. Here, a material satisfying these requirements for osteochondral regeneration is developed by integrating osteoconductive hydroxyapatite (HAp) with a chondroconductive shape memory polymer (SMP). The shape memory function-derived fixity and recovery of the scaffold enabled minimally invasive deployment and expansion to fill irregular defects. The crystalline phases on the SMP surface inhibited cell aggregation by suppressing water penetration and subsequent protein adsorption. However, HAp conjugation SMP (H-SMP) enhanced surface roughness and consequent cell-matrix interactions by limiting cell aggregation using crystal peaks. After mouse subcutaneous implantation, hydrolytic H-SMP accelerated scaffold degradation compared to that by the minimal degradation observed for SMP alone for two months. H-SMP and SMP are found to promote osteogenesis and chondrogenesis, respectively, in vitro and in vivo, including the regeneration of rat osteochondral defects using the binary scaffold form, suggesting that this material is promising for osteochondral regeneration.

Psychometric validation of the Positive Drinking Consequences Questionnaire in adolescents.

BACKGROUND: The Positive Drinking Consequences Questionnaire (PDCQ) was developed to measure positive consequences of alcohol use endorsed by college drinkers. Efforts to assess positive drinking consequences experienced by adolescents have been much more limited. The aim of the present study was to advance the psychometric testing and evaluation of the factor structure of the PDCQ in adolescents. METHODS: The current sample consisted of 173 adolescents at T1 (mean age = 15 years, range = 13-17; 61% female) who reported alcohol use in the past 12 months. Data were collected at two time points over a 12-month interval in the United States. Confirmatory factor analyses, internal consistency, test-retest reliability, and discriminant, concurrent, predictive, and incremental validity were tested. RESULTS: Our analyses supported four factors of positive alcohol-related consequences: sociability, liquid courage, sexual enhancement, and tension reduction. Internal consistency was moderate to high (α = 0.78-0.94, ω = 0.86-0.91 at T1; α = 0.59-0.93, ω = 0.85-0.93 at T2). Test-retest reliability was fair to good (ICC = 0.46-0.55). The PDCQ total and subscale factor scores demonstrated discriminant validity from negative alcohol expectancy. PDCQ total and subscale factor scores were positively associated with current alcohol consumption (ρs = 0.19-0.50 at T1; ρs = 0.17-0.46 at T2), indicating concurrent validity. Predictive validity analyses showed that the overall PDCQ scale score and the sociability subscale positively predicted maximum drinks 1 year later (ρs = 0.18-0.22). However, the sexual enhancement subscale was negatively predictive of typical drinking frequency 1 year later. Finally, the PDCQ showed incremental validity for concurrent alcohol consumption beyond that for alcohol expectancies and drinking motives. CONCLUSION: The present findings support for the reliability and validity of PDCQ for use in adolescents where it may have utility as an assessment tool for characterizing various aspects of positive drinking.

Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue.

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.

Swd2/Cps35 determines H3K4 tri-methylation via interactions with Set1 and Rad6.

BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.

Nurses' media competency: A concept analysis.

OBJECTIVES: To analyze and define the concept of nurses' media competency. DESIGN: Concept analysis. DATA SOURCES: We conducted a literature search in PubMed, CINAHL, PsycInfo, and RISS International, as well as a hand-search, for relevant articles published between January 1990 and April 2023. A total of 57 articles related to nurses' media competency, published in English or Korean, were included in this study. REVIEW METHODS: We used Walker and Avant's method of concept analysis to identify the defining attributes, antecedents, and consequences of the concept. RESULTS: The seven defining attributes of nurses' media competency were networking with members of the media, selecting the appropriate media platform, considering that the target audience is the public, creating one's own media products, delivering intended messages through the media, monitoring and responding to the media, and maintaining professional dignity. Antecedents of the concept included cultivation of desirable nursing professionalism, critical evaluation of policies and issues, recognition of media influence, establishment of education and guidelines for media use, and having facilities and availability of technologies for media use. Consequences of the concept were improved influence of individual nurses, enhanced public awareness of the nursing profession, stronger networks and collaboration among professionals, and contributions to the promotion of public health. CONCLUSIONS: This concept analysis presents a theoretical definition of nurses' media competency that can provide guidance on how to educate nurses to develop media competency and how to measure nurses' media competency.

Multiplex Detection of Foodborne Pathogens using 3D Nanostructure Swab and Deep Learning-Based Classification of Raman Spectra.

Proactive management of foodborne illness requires routine surveillance of foodborne pathogens, which requires developing simple, rapid, and sensitive detection methods. Here, a strategy is presented that enables the detection of multiple foodborne bacteria using a 3D nanostructure swab and deep learning-based Raman signal classification. The nanostructure swab efficiently captures foodborne pathogens, and the portable Raman instrument directly collects the Raman signals of captured bacteria. a deep learning algorithm has been demonstrated, 1D convolutional neural network with binary labeling, achieves superior performance in classifying individual bacterial species. This methodology has been extended to mixed bacterial populations, maintaining accuracy close to 100%. In addition, the gradient-weighted class activation mapping method is used to provide an investigation of the Raman bands for foodborne pathogens. For practical application, blind tests are conducted on contaminated kitchen utensils and foods. The proposed technique is validated by the successful detection of bacterial species from the contaminated surfaces. The use of a 3D nanostructure swab, portable Raman device, and deep learning-based classification provides a powerful tool for rapid identification (≈5 min) of foodborne bacterial species. The detection strategy shows significant potential for reliable food safety monitoring, making a meaningful contribution to public health and the food industry.

New strain Brevibacillus laterosporus TSA31-5 produces both brevicidine and brevibacillin, exhibiting distinct antibacterial modes of action against Gram-negative and Gram-positive bacteria.

The growing prevalence of antibiotic resistance has made it imperative to search for new antimicrobial compounds derived from natural products. In the present study, Brevibacillus laterosporus TSA31-5, isolated from red clay soil, was chosen as the subject for conducting additional antibacterial investigations. The fractions exhibiting the highest antibacterial activity (30% acetonitrile eluent from solid phase extraction) were purified through RP-HPLC. Notably, two compounds (A and B) displayed the most potent antibacterial activity against both Escherichia coli and Staphylococcus aureus. ESI-MS/MS spectroscopy and NMR analysis confirmed that compound A corresponds to brevicidine and compound B to brevibacillin. Particularly, brevicidine displayed notable antibacterial activity against Gram-negative bacteria, with a minimum inhibitory concentration (MIC) range of 1-8 µg/mL. On the other hand, brevibacillin exhibited robust antimicrobial effectiveness against both Gram-positive bacterial strains (MIC range of 2-4 µg/mL) and Gram-negative bacteria (MIC range of 4-64 µg/mL). Scanning electron microscopy analysis and fluorescence assays uncovered distinctive morphological alterations in bacterial cell membranes induced by brevicidine and brevibacillin. These observations imply distinct mechanisms of antibacterial activity exhibited by the peptides. Brevicidine exhibited no hemolysis or cytotoxicity up to 512 µg/mL, comparable to the negative control. This suggests its promising therapeutic potential in treating infectious diseases. Conversely, brevibacillin demonstrated elevated cytotoxicity in in vitro assays. Nonetheless, owing to its noteworthy antimicrobial activity against pathogenic bacteria, brevibacillin could still be explored as a promising antimicrobial agent.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aß42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. Methods: Aß42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aß42/40 testing. Results: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs. negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. Conclusion: High-throughput plasma Aß42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.

A Comparison of 2 Cage Sizes in Biportal Endoscopic Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: This study compared the fusion and subsidence rate and clinical outcomes when using different-sized static PEEK cages in BE-TLIF. SUMMARY OF BACKGROUND DATA: Biportal endoscopic techniques for transforaminal lumbar interbody fusion (BE-TLIF) have been shown to have similar clinical and fusion outcomes with faster clinical recovery in comparison to tubular surgery. Subsidence of the interbody, however, could be a complication. METHODS: Patients who underwent 1 or 2 level BE-TLIF for degenerative and isthmic spondylolisthesis between January 2019 and January 2022 were included. A 32×10 mm cage (group A) and a 40×15 mm cage (group B) were compared. The visual analog scale (VAS) for back and leg symptoms, and Oswestry disability index (ODI) were collected. Plain radiographs and computed tomography assessed fusion and subsidence at a minimum of 12 months. RESULTS: Of the 69 enrolled patients, 39 group A patients (51 levels) and 30 group B patients (32 levels) were compared. The operation time per level was 123 ± 15.8 and 138 ± 10.5 minutes per fusion level in groups A and B, respectively (P < 0.05). ODI improved from 64.8 ± 6.2 to 15.7 ± 7.1 in group A and from 65.3 ± 5.6 to 15.1 ± 6.3 in group B at the final follow-up (P < 0.05). VAS leg and back score improvement between the groups did not differ; however, the 3-month postoperative VAS back improvement was significantly higher in group B. The final fusion rate at the final follow-up did not significantly differ; however, the fusion ratio at 1 year was higher in group B (P < 0.05). Subsidence occurred in 5 cases (9.8%) in group A and none in group B (P < 0.05). CONCLUSION: BE-TLIF using a larger cage can be performed safely with similar patient-reported outcome measures with a faster fusion rate with less subsidence risk. LEVEL OF STUDY: III.

New plasma LC-MS/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer's disease risk assessment.

Early detection of Alzheimer's disease (AD) represents an unmet clinical need. Beta-amyloid (Aß) plays an important role in AD pathology, and the Aß42/40 peptide ratio is a good indicator for amyloid deposition. In addition, variants of the apolipoprotein E (APOE) gene are associated with variable AD risk. Here, we describe the development and validation of high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for plasma Aß40 and Aß42 quantitation, as well as apolipoprotein E (ApoE) proteotype determination as a surrogate for APOE genotype. Aß40 and Aß42 were simultaneously immunoprecipitated from plasma, proteolytically digested, and quantitated by LC-MS/MS. ApoE proteotype status was qualitatively assessed by targeting tryptic peptides from the ApoE2, ApoE3, and ApoE4 proteoforms. Both assays were validated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Within-run precision was 1.8%-4.2% (Aß40), 1.9%-7.2% (Aß42), and 2.6%-8.3% (Aß42/40 ratio). Between-run precision was 3.5%-5.9% (Aß40), 3.8%-8.0% (Aß42), and 3.3%-8.7% (Aß42/40 ratio). Both Aß40 and Aß42 were linear from 10 to 2500 pg/mL. Identified ApoE proteotypes had 100% concordance with APOE genotypes. We have developed a precise, accurate, and sensitive high-throughput LC-MS/MS assay for plasma Aß40, Aß42, and proteoforms of ApoE.

Early Physiologic Numerical and Waveform Characteristics of Simulated Hemorrhagic Events With Healthy Volunteers Donating Blood.

OBJECTIVES: Early signs of bleeding are often masked by the physiologic compensatory responses delaying its identification. We sought to describe early physiologic signatures of bleeding during the blood donation process. SETTING: Waveform-level vital sign data including electrocardiography, photoplethysmography (PPG), continuous noninvasive arterial pressure, and respiratory waveforms were collected before, during, and after bleeding. SUBJECTS: Fifty-five healthy volunteers visited blood donation center to donate whole blood. INTERVENTION: After obtaining the informed consent, 3 minutes of resting time was given to each subject. Then 3 minutes of orthostasis was done, followed by another 3 minutes of resting before the blood donation. After the completion of donating blood, another 3 minutes of postbleeding resting time, followed by 3 minutes of orthostasis period again. MEASUREMENTS AND MAIN RESULTS: From 55 subjects, waveform signals as well as numerical vital signs (heart rate [HR], respiratory rate, blood pressure) and clinical characteristics were collected, and data from 51 subjects were analyzable. Any adverse events (AEs; dizziness, lightheadedness, nausea) were documented. Statistical and physiologic features including HR variability (HRV) metrics and other waveform morphologic parameters were modeled. Feature trends for all participants across the study protocol were analyzed. No significant changes in HR, blood pressure, or estimated cardiac output were seen during bleeding. Both orthostatic challenges and bleeding significantly decreased time domain and high-frequency domain HRV, and PPG amplitude, whereas increasing PPG amplitude variation. During bleeding, time-domain HRV feature trends were most sensitive to the first 100 mL of blood loss, and incremental changes of different HRV parameters (from 300 mL of blood loss), as well as a PPG morphologic feature (from 400 mL of blood loss), were shown with statistical significance. The AE group (n = 6) showed decreased sample entropy compared with the non-AE group during postbleed orthostatic challenge (p = 0.003). No significant other trend differences were observed during bleeding between AE and non-AE groups. CONCLUSIONS: Various HRV-related features were changed during rapid bleeding seen within the first minute. Subjects with AE during postbleeding orthostasis showed decreased sample entropy. These findings could be leveraged toward earlier identification of donors at risk for AE, and more broadly building a data-driven hemorrhage model for the early treatment of critical bleeding.

An epitope-tagged Swd2 reveals the different requirements of Swd2 concentration in H3K4 methylation and viability.

Swd2/Cps35 is a common component of the COMPASS H3K4 methyltransferase and CPF transcription termination complex in Saccharomyces cerevisiae. The deletion of SWD2 is lethal, which results from transcription termination defects in snoRNA genes. This study isolated a yeast strain that showed significantly reduced protein level of Swd2 following epitope tagging at its N-terminus (9MYC-SWD2). The reduced level of Swd2 in the 9MYC-SWD2 strain was insufficient for the stability of the Set1 H3K4 methyltransferase, H3K4me3 and snoRNA termination, but the level was enough for viability and growth similar to the wildtype strain. In addition, we presented the genes differentially regulated by the essential protein Swd2 under optimal culture conditions for the first time. The expression of genes known to be decreased in the absence of Set1 and H3K4me3, including NAD biosynthetic process genes and histone genes, was decreased in the 9MYC-SWD2 strain, as expected. However, the effects of Swd2 on the ribosome biogenesis (RiBi) genes were opposite to those of Set1, suggesting that the expression of RiBi genes is regulated by more complex relationship between COMPASS and other Swd2-containing complexes. These data suggest that different concentrations of Swd2 are required for its roles in H3K4me3 and viability and that it may be either contributory or contrary to the transcriptional regulation of Set1/H3K4me3, depending on the gene group.

Nanotopology-Enabled On-Site Pathogen Detection for Managing Atopic Dermatitis.

Atopic dermatitis (AD), a prevalent skin condition often complicated by microbial infection, poses a significant challenge in identifying the responsible pathogen for its effective management. However, a reliable, safe tool for pinpointing the source of these infections remains elusive. In this study, a novel on-site pathogen detection that combines chemically functionalized nanotopology with genetic analysis is proposed to capture and analyze pathogens closely associated with severe atopic dermatitis. The chemically functionalized nanotopology features a 3D hierarchical nanopillar array (HNA) with a functional polymer coating, tailored to isolate target pathogens from infected skin. This innovative nanotopology demonstrates superior pathogenic capture efficiency, favorable entrapment patterns, and non-cytotoxicity. An HNA-assembled stick is utilized to directly retrieve bacteria from infected skin samples, followed by extraction-free quantitative loop-mediated isothermal amplification (direct qLAMP) for validation. To mimic human skin conditions, porcine skin is employed to successfully capture Staphylococcus aureus, a common bacterium exacerbating AD cases. The on-site detection method exhibits an impressive detection limit of 103 cells mL-1. The HNA-assembled stick represents a promising tool for on-site detection of bacteria associated with atopic dermatitis. This innovative approach enables to deepen the understanding of AD pathogenesis and open avenues for more effective management strategies for chronic skin conditions.

Exploring Nursing Research Culture in Clinical Practice: Qualitative Ethnographic Study.

BACKGROUND: Cultivating a positive research culture is considered the key to facilitating the utilization of research findings. In the realm of clinical nursing research, nurses conducting research may find the utilization of findings challenging due to the lack of a positive research culture. OBJECTIVE: This study aims to identify and describe the sociocultural context of nursing research in a clinical setting at a Korean tertiary hospital. METHODS: We included participant observation and ethnographic interviews with 6 registered nurses working in a medical-surgical unit in a Korean tertiary hospital who had experience conducting nursing research in clinical settings in this qualitative ethnographic study. The study was conducted from April 2022 to May 2022. Data analysis was conducted using Spradley's ethnographic approach, which includes domain analysis, taxonomic analysis, componential analysis, and theme analysis, and occurred concurrently with data collection. RESULTS: The overarching theme identified for nursing research culture in clinical practice was the development of a driving force for growth within the clinical environment. This theme encompasses (1) balancing positive and negative influences in the research process, (2) fostering transformational change for both nurses and patients, and (3) promoting complementary communication among nurses. CONCLUSIONS: Clinical research plays a vital role in nursing practice that requires a balance of supportive elements, such as patient-driven research questions and hospital research support, with practical challenges such as shift work and high work intensity. This study found that a positive clinical nursing research culture can serve as a unifying bridge, connecting researchers, patients, who serve as both the origin and ultimate beneficiaries of research, and hospitals that facilitate research endeavors. Future research should explore whether the themes derived from this study fully reflect a clinical nursing research culture comprising patients, nurses, and the hospital environment and determine what requirements are needed to establish such a nursing research culture.

Inducing Pluripotency in Somatic Cells: Historical Perspective and Recent Advances.

Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating in vitro disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.

Agathobaculum butyriciproducens improves ageing-associated cognitive impairment in mice.

AIMS: The gut microbiota is increasingly recognised as a pivotal regulator of immune system homeostasis and brain health. Recent research has implicated the gut microbiota in age-related cognitive impairment and dementia. Agathobaculum butyriciproducens SR79 T (SR79), which was identified in the human gut, has been reported to be beneficial in addressing cognitive deficits and pathophysiologies in a mouse model of Alzheimer's disease. However, it remains unknown whether SR79 affects age-dependent cognitive impairment. MAIN METHOD: To explore the effects of SR79 on cognitive function during ageing, we administered SR79 to aged mice. Ageing-associated behavioural alterations were examined using the open field test (OFT), tail suspension test (TST), novel object recognition test (NORT), Y-maze alternation test (Y-maze), and Morris water maze test (MWM). We investigated the mechanisms of action in the gut and brain using molecular and histological analyses. KEY FINDINGS: Administration of SR79 improved age-related cognitive impairment without altering general locomotor activity or depressive behaviour in aged mice. Furthermore, SR79 increased mature dendritic spines in the pyramidal cells of layer III and phosphorylation of CaMKIIα in the cortex of aged mice. Age-related activation of astrocytes in the cortex of layers III-V of the aged brain was reduced following SR79 administration. Additionally, SR79 markedly increased IL-10 production and Foxp3 and Muc2 mRNA expression in the colons of aged mice. SIGNIFICANCE: These findings suggest that treatment with SR79 may be a beneficial microbial-based approach for enhancing cognitive function during ageing.