Cell-based artificial platelet production has made remarkable progress over the past three decades, driven by the need for safe and stable platelet sources in the face of donor limitations and transfusion-related risks. This review provides a chronological overview of the evolution of in vitro platelet production from various cell sources (CD34+ hematopoietic stem cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and others) and highlights key advances in the field. We outline developments from the foundational experiments of the 1990s, through the introduction of iPSCs in the mid-2000s, to the adoption of three-dimensional culture and bioreactor technologies in the late 2010s and the emergence of clinical trials in the 2020s. In addition, we discuss future perspec‑ tives, including the role of advanced gene editing and scalable biomanufacturing technologies in accelerating clinical translation. This comprehensive review underscores the promise of artificial platelet production technologies for clini‑ cal applications and discusses the remaining challenges, such as scalability, cost-effectiveness, and regulatory hurdles.The recent completion of the first human clinical trials using iPSC-derived platelets marks a significant milestone, pointing to a future in which patient-specific or human leukocyte antigen-universal platelets may be transformed into transfusion medicine and regenerative therapies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, leading to the coronavirus disease 2019 (COVID-19) pandemic. Because a significant proportion of the COVID-19 confirmed cases were concentrated in the capital metropolitan area of South Korea, and a large proportion of the population in the area had been adequately vaccinated against COVID-19, we conducted a seroprevalence surveillance study focusing on the residents of the capital metropolitan area in South Korea. Methods: We used a quota-sampling method to obtain blood samples from 1,000 individuals per round, equally stratified across seven age categories and sexes and regions, from five medical institutions located within the capital metropolitan area of South Korea. During five consecutive months (rounds) between January 2022 and May 2022, a total of 5,000 samples were analyzed for anti-spike (S) and anti-nucleocapsid (N) antibodies. Results: High anti-S seropositivity was observed in all age groups, which corresponded to the vaccine coverage during the study period. Both the cumulative incidence based on polymerase chain reaction (PCR) and the estimated seroprevalence based on anti-N seropositivity increased in the fourth and fifth rounds, which corresponded to April 2022 and May 2022. Seroprevalence coincided with the cumulative incidence during the first three rounds, but exceeded from the fourth survey onwards when infection with omicron variants was increased rapidly in Korea. Conclusion Seroprevalence confirmed the number of infection cases outside of PCR testing-based surveillance. Seroepidemiological surveillance can help us understand vaccine responses and detect hidden infections, thereby providing appropriate public health guidance for achieving population-level immunity.

Background: This study examined the impact of the performance improvement and patient safety (PIPS) program implemented in 2015 on outcomes for trauma patients in a regional trauma center established by a government-led project for a national trauma system in Korea. Methods: The PIPS program was based on guidelines by the World Health Organization and American College of Surgeons. The corrective strategies were proceeded according to the loop closure principle: data-gathering and monitoring, identification of preventable trauma deaths (PTDs), evaluation of preventable factors, analysis of findings, and corrective action plans. We established guidelines and protocols for trauma care, conducted targeted education and peer review presentations for problematic cases, and enhanced resources for improvement accordingly. A comparative analysis was performed on trauma outcomes over a four-year period (2015–2018) since implementing the PIPS program, including the number of trauma team activation and admissions, time factors related to resuscitation, ventilator duration, and the rate of PTDs. Results: Human resources in the center significantly increased during the period; attending surgeons responsible for trauma resuscitation from 6 to 11 and trauma nurses from 85 to 218. Trauma admissions (from 2,166 to 2,786), trauma team activations (from 373 to 1,688), and severe cases (from 22.6 to 33.8%) significantly increased (all P < 0.001). Time to initial resuscitation and transfusion significantly decreased from 120 to 36 minutes (P < 0.001) and from 39 to 16 minutes (P < 0.001). Time to surgery for hemorrhage control and decompressive craniotomy improved from 99 to 54 minutes (P < 0.001) and 181 to 135 minutes (P = 0.042). Ventilator duration and rate of PTDs significantly decreased from 6 to 4 days (P = 0.001) and 22.2% to 8.4% (P = 0.008). Conclusion Implementation of the PIPS program resulted in improvements in outcomes at a regional trauma center that has just been opened in Korea. Further establishment of the PIPS program is required for optimal care of trauma patients.

Background: This study examined the impact of the performance improvement and patient safety (PIPS) program implemented in 2015 on outcomes for trauma patients in a regional trauma center established by a government-led project for a national trauma system in Korea. Methods: The PIPS program was based on guidelines by the World Health Organization and American College of Surgeons. The corrective strategies were proceeded according to the loop closure principle: data-gathering and monitoring, identification of preventable trauma deaths (PTDs), evaluation of preventable factors, analysis of findings, and corrective action plans. We established guidelines and protocols for trauma care, conducted targeted education and peer review presentations for problematic cases, and enhanced resources for improvement accordingly. A comparative analysis was performed on trauma outcomes over a four-year period (2015–2018) since implementing the PIPS program, including the number of trauma team activation and admissions, time factors related to resuscitation, ventilator duration, and the rate of PTDs. Results: Human resources in the center significantly increased during the period; attending surgeons responsible for trauma resuscitation from 6 to 11 and trauma nurses from 85 to 218. Trauma admissions (from 2,166 to 2,786), trauma team activations (from 373 to 1,688), and severe cases (from 22.6 to 33.8%) significantly increased (all P < 0.001). Time to initial resuscitation and transfusion significantly decreased from 120 to 36 minutes (P < 0.001) and from 39 to 16 minutes (P < 0.001). Time to surgery for hemorrhage control and decompressive craniotomy improved from 99 to 54 minutes (P < 0.001) and 181 to 135 minutes (P = 0.042). Ventilator duration and rate of PTDs significantly decreased from 6 to 4 days (P = 0.001) and 22.2% to 8.4% (P = 0.008). Conclusion Implementation of the PIPS program resulted in improvements in outcomes at a regional trauma center that has just been opened in Korea. Further establishment of the PIPS program is required for optimal care of trauma patients.

OBJECTIVES: To circumvent the limitations of the current golden standard method, colony-forming unit (CFU) assay, for viability of Bacille Calmette–Guérin (BCG) vaccines, we developed a new method to rapidly and accurately determine the potency of BCG vaccines. METHODS: Based on flow cytometry (FACS) and fluorescein diacetate (FDA) as the most appropriate fluorescent staining reagent, 17 lots of BCG vaccines for percutaneous administration and 5 lots of BCG vaccines for intradermal administration were analyzed in this study. The percentage of viable cells measured by flow cytometry along with the total number of organisms in BCG vaccines, as determined on a cell counter, was used to quantify the number of viable cells. RESULTS: Pearson correlation coefficients of FACS and CFU assays for percutaneous and intradermal BCG vaccines were 0.6962 and 0.7428, respectively, indicating a high correlation. The coefficient of variation value of the FACS assay was less than 7%, which was 11 times lower than that of the CFU assay. CONCLUSION: This study contributes to the evaluation of new potency test method for FACS-based determination of viable cells in BCG vaccines. Accordingly, quality control of BCG vaccines can be significantly improved.
Administration, Cutaneous ; BCG Vaccine ; Cell Count ; Flow Cytometry* ; Fluorescein ; Methods ; Mycobacterium bovis ; Quality Control ; Stem Cells ; Vaccine Potency ; Vaccines*

In this article, a part of fund and grant supports was omitted unintentionally.

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Carcinogenesis ; Herpesviridae ; Humans ; Hyperplasia* ; Immunohistochemistry ; MicroRNAs ; Nanoparticles ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction

PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. RESULTS: Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. CONCLUSION: Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.
Aged ; Biomarkers/metabolism ; Carcinoma, Transitional Cell/genetics/*metabolism/pathology ; Carnitine/*analogs & derivatives/genetics/metabolism ; Case-Control Studies ; Female ; Humans ; Male ; Metabolic Networks and Pathways/*physiology ; Middle Aged ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Urinary Bladder Neoplasms/genetics/*metabolism/pathology

PURPOSE: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. METHODS: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. RESULTS: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. CONCLUSIONS: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.
Biomarkers ; Biopsy ; Cohort Studies ; Diagnosis ; Early Diagnosis ; Herpes Simplex ; Humans ; Microarray Analysis ; MicroRNAs* ; Passive Cutaneous Anaphylaxis ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Prostatic Neoplasms* ; Sensitivity and Specificity ; Simplexvirus ; Urologic Diseases

BACKGROUND: We investigated the rates of fecal transmission of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE) among patients admitted to intensive care units (ICUs). METHODS: From June to August 2012, rectal cultures were acquired from all patients at ICU admission. For patients not carrying ESBL-E or CRE at admission, follow-up cultures were performed to detect acquisition. A chromogenic assay was used to screen for ESBL-E and CRE. Bacterial species identification and antibiotic susceptibility tests were performed using the Vitek 2 system (bioMerieux, France). ESBL genotypes were determined by PCR, and clonal relatedness of the isolates was assessed by pulsed-field gel electrophoresis. RESULTS: Out of 347 ICU admissions, 98 patients were found to be carriers of ESBL-E (28.2%, 98/347). Follow-up cultures were acquired from 91 of the patients who tested negative for ESBL-E at admission; the acquisition rate in this group was 12.1% (11/91), although none was a nosocomial transmission. For CRE, the prevalence of fecal carriage was 0.3% (1/347), and the acquisition rate was 2.9% (4/140). None of the CRE isolates were carbapenemase-producers. CONCLUSIONS: The high prevalence of ESBL-E carriage on admission (28.2%), coupled with rare nosocomial transmission and the very low carriage rate of CRE (0.3%), challenge the routine use of active surveillance in non-epidemic settings. Nevertheless, passive surveillance measures, such as rapid and accurate screening of clinical specimens, will be critical for controlling the spread of CRE.
Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/*metabolism ; Carbapenems/*pharmacology ; Carrier State/epidemiology ; Cross Infection/epidemiology/*transmission ; DNA, Bacterial/analysis ; Drug Resistance, Bacterial/drug effects ; Electrophoresis, Gel, Pulsed-Field ; Enterobacteriaceae/enzymology/genetics/*physiology ; Enterobacteriaceae Infections/epidemiology/*transmission ; Feces/*microbiology ; Genotype ; Humans ; Intensive Care Units ; Polymerase Chain Reaction ; Prevalence ; Republic of Korea/epidemiology ; beta-Lactamases/*metabolism