Survey on caregiver competency and retraining needs.

OBJECTIVES: This study investigated caregivers' job image, abilities, and educational needs, which are rapidly increasing owing to an aging society. DESIGN: A self-administered written survey was conducted at 12 general hospitals in Korea from February 1, 2022 to March 15, 2023. SAMPLE: A total of 451 caregivers participated in the survey as subjects of analysis, and 560 nurses participated as external observers. MEASUREMENTS: The caregivers' self-assessment results regarding job performance, educational needs, and retraining needs were compared with those of external observers. RESULTS: Caregivers evaluated themselves significantly higher in all areas of job performance compared to the evaluations of external observers. In particular, the caregivers' self-evaluation of their abilities in "Recording and Reporting," "Basic Resuscitation," "Safety and Infection Control," and "Understanding Major Illnesses" was different from the evaluation of nurses. Both the caregivers and external observers agreed on the need for caregiver retraining, with 1-2 hours of supplementary training every 12 months being the most preferred amount of retraining. CONCLUSIONS: There was a significant difference between caregivers' self-evaluations of their capabilities and the external observers' evaluations. Therefore, systematic professional caregiver retraining is necessary.

Comparative analysis of F-18 FDG PET/CT images between scrub typhus and systemic lupus erythematosus.

This study evaluated the use of F-18 fluorodeoxyglucose (FDG) PET/CT imaging to differentiate between scrub typhus and systemic lupus erythematosus (SLE) in patients presenting with lymphadenopathy. We carried out a retrospective analysis of 18 scrub typhus patients and seven SLE patients, using various imaging parameters, including lymph node size, spleen and liver lengths, the distance between the two farthest lesions (Dmax), and assessments of glucose metabolism. On FDG PET images, we measured the maximum standardized uptake value (SUVmax) of the lymph nodes, spleen, and liver and the mean standardized uptake value (SUVmean) of the liver and spleen. The Dmax values of scrub typhus patients were significantly longer than those of SLE patients, indicating that lymphadenopathy is more generalized in the patients with scrub typhus. The SUVmax values for the lymph node, spleen, and liver were also higher in patients with scrub typhus, while the SUVmean of the liver and spleen did not differ between the two groups. This study is the first to compare FDG PET/CT images between these two conditions, suggesting the potential of this imaging modality to provide critical diagnostic distinctions.

Effectiveness of a Fire Disaster PFA Simulation Game: A Single-Blinded Trial.

OBJECTIVE: As societies become more complex, disasters are increasing in frequency and magnitude. To respond to the psychological problems that may arise in such situations, it is necessary to develop the psychological first aid (PFA) training program that is more engaging for disaster relief workers and less limited in time and space. This study aimed to investigate the effectiveness of a web-based PFA simulation game for disaster relief workers to provide to fire disaster victims. METHODS: This was a non-randomized controlled experimental study with 30 participants in the experimental and control groups. The experimental group learned through the web-based PFA simulation game developed in this study, and the control group was provided with written educational materials regarding general disaster. The effects of time between groups and interaction between groups were tested. RESULTS: Compared to the control group, the experimental group showed significant effects on core competencies in disaster response, self-efficacy, and problem-solving process, and the persistence of the effects was also significantly different. CONCLUSION: The web-based PFA simulation game was found to be effective in improving core competencies in disaster response, self-efficacy, and problem-solving process of disaster relief workers. These results suggest that simulation games can be an effective learning method for learning PFA for disaster relief workers. Since it is difficult to learn through direct participation in disaster situations, a web-based simulation game may be a more effective way to improve and maintain the competence of PFA.

Efficacy of a virtual nursing simulation-based education to provide psychological support for patients affected by infectious disease disasters: a randomized controlled trial.

BACKGROUND: Virtual simulation-based education for healthcare professionals has emerged as a strategy for dealing with infectious disease disasters, particularly when training at clinical sites is restricted due to the risk of infection and a lack of personal protective equipment. This research evaluated a virtual simulation-based education program intended to increase nurses' perceived competence in providing psychological support to patients affected by infectious disease disasters. METHODS: The efficacy of the program was evaluated via a randomized controlled trial. We recruited 104 nurses for participation in the study and allocated them randomly and evenly to an experimental group and a control group. The experimental group was given a web address through which they could access the program, whereas the control group was provided with a web address that directed them to text-based education materials. Data were then collected through an online survey of competence in addressing disaster mental health, after which the data were analyzed using the Statistical Package for the Social Sciences(version 23.0). RESULTS: The analysis showed that the experimental group's disaster mental health competence (F = 5.149, p =.026), problem solving process (t = 3.024, p =.003), self-leadership (t = 2.063, p =.042), learning self-efficacy (t = 3.450, p =.001), and transfer motivation (t = 2.095, p =.039) significantly statistically differed from those of the control group. CONCLUSIONS: A virtual nursing simulation-based education program for psychological support can overcome limitations of time and space. The program would also be an effective learning resource during infectious disease outbreaks. CLINICAL TRIAL REGISTRATION: This Korean clinical trial was retrospectively registered (21/11/2023) in the Clinical Research Information Service ( https://cris.nih.go.kr ) with trial registration number KCT0008965.

A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis.

BACKGROUND: Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits. METHODS: In this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 [worst itch imaginable]) from baseline to month 6 among patients with a baseline score of at least 4 (indicating moderate-to-severe pruritus). RESULTS: Of the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy. A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001). Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001). Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, -3.2 vs. -1.7; least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5, P = 0.005). Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively. CONCLUSIONS: In this trial involving patients with primary biliary cholangitis, the percentage of patients who had a biochemical response and alkaline phosphatase normalization was significantly greater with seladelpar than with placebo. Seladelpar also significantly reduced pruritus among patients who had moderate-to-severe pruritus at baseline. The incidence and severity of adverse events were similar in the two groups. (Funded by CymaBay Therapeutics; RESPONSE ClinicalTrials.gov number, NCT04620733; EudraCT number, 2020-004348-27.).

The Development, Implementation, and Evaluation of a Geriatric Disaster Nursing Simulation Intervention With Supportive Debriefing.

INTRODUCTION: Geriatric disaster nursing simulation curriculum use scenarios with trauma-based topics that may contribute to lack of psychological safety in learners. This learning condition lowers students' self-efficacy, so supportive debriefing is needed to provide psychological safety for learners. The aims of this study are to develop and apply a geriatric disaster nursing simulation and to evaluate the effectiveness of a supportive debriefing model on psychological safety, learning self-efficacy, and counseling self-efficacy. METHODS: A geriatric nursing simulation scenario, checklists, and a standardized patient were developed based on the Analysis-Design-Development-Implementation-Evaluation model. Nursing students were recruited as participants and randomly assigned to either the experimental group, conventional group, or control group. All 3 groups participated in the same geriatric disaster nursing simulation scenario, after which the experimental group used a supportive debriefing model-the SENSE (share-explore-notice-support-extend) model. The conventional group used a common debriefing model, the GAS (gathering-analyzing-summarizing) model, and the control group received simple comments with no debriefing model. The effects of the debriefing models on psychological safety, learning self-efficacy, and counseling self-efficacy were measured by self-report questionnaires. The aggregate scores of the measures were 222 for counseling self-efficacy, 70 for learning self-efficacy, and 50 for psychological safety. Higher scores within these measures corresponded to heightened capabilities. RESULTS: The mean score of counseling self-efficacy in the SENSE model group was significantly increased after the simulation with the supportive debriefing from 142.80 ± 11.43 to 164.53 ± 15.48 (Z = -3.411, P = 0.001). In addition, the SENSE model group and the GAS model group had significantly higher scores in counseling self-efficacy, learning self-efficacy, and psychological safety than those of the control group. However, the SENSE model group had a significantly higher score in psychological safety than that of the GAS model group. CONCLUSIONS: The SENSE debriefing model is recommended as a supportive debriefing model to foster students' psychological safety in disaster nursing simulations.

Professional quality of life, resilience, posttraumatic stress and leisure activity among intensive care unit nurses.

BACKGROUND: Nurses working in the intensive care unit (ICU) often experience posttraumatic stress due to being exposed to pain, death, disease and surrogate trauma. Thus, it is necessary to investigate ways to enhance their coping abilities and improve their professional quality of life. AIM: This study explores factors related to professional quality of life, resilience and posttraumatic stress of ICU nurses and provides basic data for the development of psychological support programmes to address. METHODS: The participants in this cross-sectional study consisted of 112 ICU nurses working at a general hospital in Seoul, Korea. Data were collected using self-report questionnaires on general characteristics, professional quality of life, resilience and posttraumatic stress and analysed using IBM SPSS for Windows version 25. FINDINGS: Professional quality of life showed a significant positive correlation with nurses' resilience, whereas posttraumatic stress was significantly negatively correlated with professional quality of life. Among participants' general characteristics, leisure activity showed the strongest positive correlation with professional quality of life and resilience and a significant negative correlation with posttraumatic stress. CONCLUSION: This study explored the correlations among resilience, posttraumatic stress and professional quality of life of ICU nurses. Further, we found that leisure activities are associated with their higher resilience and lower posttraumatic stress. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Policy development and organisational supports are required to promote various club activities and stress reduction programmes for clinical nurses in order to increase their professional quality of life and resilience as well as prevent posttraumatic stress.

Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis.

BACKGROUND: Seladelpar is a potent and selective peroxisome proliferator-activated receptor-δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti-cholestatic, anti-inflammatory and anti-pruritic effects. AIMS: To evaluate the long-term safety and efficacy of seladelpar in patients with PBC. METHODS: In an open-label, international, long-term extension study, patients with PBC completing seladelpar lead-in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non-alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years. RESULTS: There were no serious treatment-related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2. CONCLUSIONS: Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. CLINICALTRIALS: gov: NCT03301506; Clinicaltrialsregister.eu: 2017-003910-16.

Seladelpar combined with complementary therapies improves fibrosis, inflammation, and liver injury in a mouse model of nonalcoholic steatohepatitis.

Seladelpar, a selective peroxisome proliferator-activated receptor δ (PPARδ) agonist, improves markers of hepatic injury in human liver diseases, but histological improvement of nonalcoholic steatohepatitis (NASH) and liver fibrosis has been challenging with any single agent. To discover how complementary agents could work with seladelpar to achieve optimal outcomes, this study evaluated a variety of therapeutics (alone and in combination) in a mouse model of NASH. Mice on a high-fat amylin liver NASH (AMLN) diet were treated for 12 wk with seladelpar, GLP-1-R (glucagon-like peptide-1 receptor) agonist liraglutide, apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib, farnesoid X receptor (FXR) agonist obeticholic acid, and with seladelpar in combination with liraglutide or selonsertib. Seladelpar treatment markedly improved plasma markers of liver function. Seladelpar alone or in combination resulted in stark reductions in liver fibrosis (hydroxyproline, new collagen synthesis rate, mRNA indices of fibrosis, and fibrosis staining) compared with vehicle and the other single agents. Robust reductions in liver steatosis were also observed. Seladelpar produced a reorganization of metabolic gene expression, particularly for those genes promoting peroxisomal and mitochondrial lipid oxidation. In summary, substantial improvements in NASH and NASH-induced fibrosis were observed with seladelpar alone and in combination with liraglutide in this model. Broad gene expression analysis suggests seladelpar should be effective in concert with diverse mechanisms of action.NEW & NOTEWORTHY NASH is a chronic, progressive, and increasingly problematic liver disease that has been resistant to treatment with individual therapeutics. In this study using a diet-induced mouse model of NASH, we found that the PPARδ agonist seladelpar reduced fibrosis and NASH pathology alone and in combinations with a GLP-1-R agonist (liraglutide) or an ASK1 inhibitor (selonsertib). Liver transcriptome analysis comparing each agent and coadministration suggests seladelpar should be effective in combination with a variety of therapeutics.

Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis.

BACKGROUND AND AIMS: Pruritus is a debilitating symptom for many people living with primary biliary cholangitis (PBC). In studies with seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, patients with PBC experienced significant improvement in pruritus and reduction of serum bile acids. Interleukin-31 (IL-31) is a cytokine known to mediate pruritus, and blocking IL-31 signaling provides relief in pruritic skin diseases. This study examined the connection between seladelpar's antipruritic effects and IL-31 and bile acid levels in patients with PBC. APPROACH AND RESULTS: IL-31 levels were quantified in serum samples from the ENHANCE study of patients with PBC receiving daily oral doses of placebo (n = 55), seladelpar 5 mg (n = 53) or 10 mg (n = 53) for 3 months, and for healthy volunteers (n = 55). IL-31 levels were compared with pruritus using a numerical rating scale (NRS, 0-10) and with bile acid levels. Baseline IL-31 levels closely correlated with pruritus NRS ( r = 0.54, p < 0.0001), and total ( r = 0.54, p < 0.0001) and conjugated bile acids (up to 0.64, p < 0.0001). Decreases in IL-31 were observed with seladelpar 5 mg (-30%, p = 0.0003) and 10 mg (-52%, p < 0.0001) versus placebo (+31%). Patients with clinically meaningful improvement in pruritus (NRS ≥ 2 decrease) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (NRS < 2 decrease). Strong correlations were observed for the changes between levels of IL-31 and total bile acids ( r = 0.63, p < 0.0001) in the seladelpar 10 mg group. CONCLUSIONS: Seladelpar decreased serum IL-31 and bile acids in patients with PBC. The reductions of IL-31 and bile acids correlated closely with each other and pruritus improvement, suggesting a mechanism to explain seladelpar's antipruritic effects.

Effects of a web-based education for community mental health case managers on physical healthcare for clients with severe mental illness.

This study aimed to develop and verify the effects of a web-based physical healthcare education program for community mental health case managers during the time of COVID-19. Six modules of mental health case management physical health education program were developed and provided using the EdWith education platform, which enables real-time streaming, lecture participant management and whether participants have watched the video and watch time. A total of 51 community mental health case managers participated in the study. Collected data were analyzed using SPSS 26.0 software. Participants of the physical healthcare education program testified increased performance in, as well as enhanced attitudes toward physical healthcare. Their confidence in physical healthcare increased significantly from that of the individuals in the control group. The web-based educational program for mental health case managers in physical healthcare may be beneficial to improving the physical health of clients with chronic mental illness.

What influenced frontline nurses' mental health during the early phase of the COVID-19 pandemic.

AIM: This cross-sectional study aimed to investigate the factors that affected the mental health of Korean nurses caring for coronavirus disease 2019 (COVID-19) patients, causing posttraumatic stress disorder, depression, anxiety, and sleep disorders. BACKGROUND: Infectious disease outbreaks like COVID-19 affect the mental health not only of those who contract the disease but also of nurses caring for affected patients. INTRODUCTION: To address health issues effectively, it is essential to comprehend how to prevent them. Therefore, it is necessary to scrutinize the origins of COVID-19-related health concerns and devise measures to prevent potential problems. METHOD: We used an online survey to collect data from 136 nurses caring for COVID-19 patients during the initial stage of the pandemic. The data were analyzed using the one-way analysis of variance and a simple logistic regression. RESULTS: The findings confirmed a high prevalence of posttraumatic stress disorder among nurses, with symptoms of depression, anxiety, and sleep problems. DISCUSSION: Our research has shown that it is important not to exacerbate the difficulties that nurses face after their activities. Therefore, it proposes for creating environmental structures that mitigate predictable challenges such as workload from various tasks, sleep disturbances, and hopelessness, rather than focusing on personal vulnerabilities. CONCLUSION: Timely attention to influencing factors can reduce the risk to nurses' mental health, so we need to plan preventive measures that reflect the influencing factors to prepare for future pandemics. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Continuous monitoring of the mental health status of nurses responding to a global health crisis and the development of appropriate psychological support programs and policies for creating a conducive work environment are necessary.

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

Neurofeedback Effect on Symptoms of Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis.

Posttraumatic stress disorder (PTSD) encompasses various psychological symptoms and a high early dropout rate due to treatment unresponsiveness. In recent years, neurofeedback has been implemented to control PTSD's psychological symptoms through physiological brain regulation. However, a comprehensive analysis concerning its efficacy is lacking. Therefore, we conducted a systematic review and meta-analysis to determine neurofeedback's effect on reducing PTSD symptoms. We analyzed randomized and non-randomized controlled trials (RCTs) from 1990 to July 2020, evaluating neurofeedback treatments for those diagnosed with PTSD and their symptoms. In addition, we calculated the standardized mean difference (SMD)using random-effects models to estimate effect sizes. We assessed ten articles comprising 276 participants, with a - 0.74 SMD (95% confidence interval = - 0.9230, - 0.5567), 42% I2, moderate effect size, and - 1.40 to -0.08 prediction intervals (PI). Neurofeedback was more effective for complex trauma PTSD patients than single trauma. Increasing and lengthening sessions are more effective than fewer, condensed ones. Neurofeedback positively affected arousal, anxiety, depression, and intrusive, numbing, and suicidal thoughts. Therefore, neurofeedback is a promising and effective treatment for complex PTSD.

Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes of Staphylococcus aureus Bacteremia.

BACKGROUND: Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. METHODS: Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. RESULTS: Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). CONCLUSION: The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.

Effects of a mental health nursing simulation for general ward nurses: A pilot study.

This study aimed to develop a mental health nursing simulation education programme for non-psychiatric nurses and verify its effects on mental health care competence, burden, and anxiety. To verify the effects of the simulation, we applied a non-equivalent control group pre-posttest research design. We developed a mental health nursing simulation using a standardized patient who presented moderate levels of anxiety and depressive mood during chemotherapy after mastectomy. The participants were nurses working at non-psychiatric wards of a general hospital in Seoul, Korea. Participants' mental health care competency scores increased by 80% in the experimental group and 15% in the control group from pre-test to posttest. Burden scores decreased by 42% in the experimental group and 4% in the control group from pre-test to posttest, and anxiety scores decreased by 77% in the experimental group and 24% in the control group. This study demonstrated the nursing simulation education programme's effectiveness as a complementary tool to improve mental health nursing care for non-psychiatric nurses.

Three-dimensional imaging and analysis of pathological tissue samples with de novo generation of citrate-based fluorophores.

Two-dimensional (2D) histopathology based on the observation of thin tissue slides is the current paradigm in diagnosis and prognosis. However, labeling strategies in conventional histopathology are limited in compatibility with 3D imaging combined with tissue clearing techniques. Here, we present a rapid and efficient volumetric imaging technique of pathological tissues called 3D tissue imaging through de novo formation of fluorophores, or 3DNFC, which is the integration of citrate-based fluorogenic reaction DNFC and tissue clearing techniques. 3DNFC markedly increases the fluorescence intensity of tissues by generating fluorophores on nonfluorescent amino-terminal cysteine and visualizes the 3D structure of the tissues to provide their anatomical morphology and volumetric information. Furthermore, the application of 3DNFC to pathological tissue achieves the 3D reconstruction for the unbiased analysis of diverse features of the disorders in their natural context. We suggest that 3DNFC is a promising volumetric imaging method for the prognosis and diagnosis of pathological tissues.