Efficacy and Safety of Low-Dose Intravesical OnabotulinumtoxinA Injections in Female Patients With Detrusor Overactivity With Detrusor Underactivity.

PURPOSE: We assessed the effectiveness and safety of using intravesical onabotulinumtoxinA (onabotA; BOTOX) injection with a low dose (75 units) for treating urinary storage symptoms in patients with detrusor overactivity with detrusor underactivity (DODU) compared to using the standard 100 units of onabotA in patients with overactive bladder (OAB). METHODS: This ambidirectional study included 121 female patients who received intravesical onabotA injections at our hospitals. A total of 87 patients with OAB and 34 patients with DODU were reviewed using a 3-day voiding diary, uroflowmetry, and questionnaires including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Patient Perception of Bladder Condition. Patients were evaluated at baseline, within 2 weeks of treatment, and beyond 3 months after treatment. RESULTS: Questionnaire scores of the DODU group demonstrated significant improvement in the short term, with a subsequent decline, but an overall improvement compared to baseline in the long term. Notably, the DODU group exhibited enhanced IPSS voiding scores after the treatment. In the OAB group, most questionnaire scores, excluding the IPSS voiding score, showed significant posttreatment improvement, which was sustained to some extent in the long term. Voiding diary parameters related to storage symptoms were enhanced in both groups. The maximum and mean flow rates decreased in the OAB group but increased in the DODU group, particularly in the short term (P=0.000). The postvoid residual volume increased in both groups after posttreatment, with a mitigated change in the long term. Safety assessments revealed manageable adverse events in both groups with comparable frequencies. CONCLUSION: Low-dose intravesical onabotA for DODU demonstrated a relatively shorter duration of efficacy than OAB. Nonetheless, the treatment improved both storage and voiding symptoms in patients with DODU without significant adverse effects.

EarlyTect BCD, a Streamlined PENK Methylation Test in Urine DNA, Effectively Detects Bladder Cancer in Patients with Hematuria.

The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube. The detection limitation of the test was approximately two genome copies of methylated PENK per milliliter of urine. In the retrospective training set (n = 105), an optimal cutoff value was determined to distinguish BC from non-BC, resulting in a sensitivity of 87.3% and a specificity of 95.2%. In the prospective validation set (n = 210, 122 Korean and 88 American patients), the overall sensitivity for detecting all stages of BC was 81.0%, with a specificity of 91.5% and an area under the curve value of 0.889. There was no significant difference between the two groups. The test achieved a sensitivity of 100% in detecting high-grade Ta and higher stages of BC. The negative predictive value of the test was 97.7%, and the positive predictive value was 51.5%. The findings of this study demonstrate that EarlyTect BCD is a highly effective noninvasive diagnostic tool for identifying BC among patients with hematuria.

AI-based betting anomaly detection system to ensure fairness in sports and prevent illegal gambling.

This study develops a solution to sports match-fixing using various machine-learning models to detect match-fixing anomalies, based on betting odds. We use five models to distinguish between normal and abnormal matches: logistic regression (LR), random forest (RF), support vector machine (SVM), the k-nearest neighbor (KNN) classification, and the ensemble model-a model optimized from the previous four. The models classify normal and abnormal matches by learning their patterns using sports betting odds data. The database was developed based on the world football league match betting data of 12 betting companies, which offered a vast collection of data on players, teams, game schedules, and league rankings for football matches. We develop an abnormal match detection model based on the data analysis results of each model, using the match result dividend data. We then use data from real-time matches and apply the five models to construct a system capable of detecting match-fixing in real time. The RF, KNN, and ensemble models recorded a high accuracy, over 92%, whereas the LR and SVM models were approximately 80% accurate. In comparison, previous studies have used a single model to examine football match betting odds data, with an accuracy of 70-80%.

Development of a Non-Contact Sensor System for Converting 2D Images into 3D Body Data: A Deep Learning Approach to Monitor Obesity and Body Shape in Individuals in Their 20s and 30s.

This study demonstrates how to generate a three-dimensional (3D) body model through a small number of images and derive body values similar to the actual values using generated 3D body data. In this study, a 3D body model that can be used for body type diagnosis was developed using two full-body pictures of the front and side taken with a mobile phone. For data training, 400 3D body datasets (male: 200, female: 200) provided by Size Korea were used, and four models, i.e., 3D recurrent reconstruction neural network, point cloud generative adversarial network, skinned multi-person linear model, and pixel-aligned impact function for high-resolution 3D human digitization, were used. The models proposed in this study were analyzed and compared. A total of 10 men and women were analyzed, and their corresponding 3D models were verified by comparing 3D body data derived from 2D image inputs with those obtained using a body scanner. The model was verified through the difference between 3D data derived from the 2D image and those derived using an actual body scanner. Unlike the 3D generation models that could not be used to derive the body values in this study, the proposed model was successfully used to derive various body values, indicating that this model can be implemented to identify various body types and monitor obesity in the future.

The Effects of an App-Based Physical Activity Program on Colorectal Cancer Patients Undergoing Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide. Oxaliplatin, which is used as adjuvant chemotherapy, affects quality of life by causing oxaliplatin-induced peripheral neuropathy in colorectal cancer patients. OBJECTIVES: This study examined the effects of an application (app)-based physical activity program for alleviating peripheral neuropathy symptoms in colorectal cancer patients undergoing chemotherapy. METHODS: This was a randomized controlled study that included 34 patients undergoing chemotherapy after being diagnosed with colorectal cancer. Outcomes were compared between patients who participated in a 6-week app-based physical activity program (experimental group; n = 17) and who received standard booklet education (control group; n = 17). Data were collected using questionnaires, and exercise time was recorded to evaluate intervention adherence. RESULTS: Significant differences were observed between the groups in peripheral neuropathy symptoms (F = 8.93, P = .002), interference with activities (Z = -2.55, P = .011), and quality of life (F = 7.65, P = .003). The experimental group showed significantly higher average exercise times at 1 to 4 weeks (Z = -2.10, P = .026), 5 to 6 weeks (Z = -4.02, P < .001), and 1 to 6 weeks (Z = -3.40, P = .001) than the control group. CONCLUSIONS: The app-based physical activity program had a positive effect on participants' exercise adherence and reduced peripheral neuropathy symptoms. Thus, we propose the adoption of a mobile health app that can be used at any time or place as an intervention for preventing or alleviating adverse effects during the treatment of cancer patients. IMPLICATIONS FOR PRACTICE: An app-based physical activity program using the mobile health app can be used as a nursing intervention to manage symptoms and increase the health behavior adherence in cancer patients.

Preclinical Study of Dual-Wavelength Light-Emitting Diode Therapy in an Osteoarthritis Rat Model.

OBJECTIVE: To evaluate the efficacy of light-emitting diode (LED) and their dual-wavelengths as a treatment strategy for osteoarthritis. METHODS: We induced osteoarthritis in male Sprague-Dawley rats by intra-articular injection of sodium iodoacetate into the right rear knee joint. The animals with lesions were divided into an untreated group and an LED-treated group (n=7 each). In the LED-treated group, the lesioned knee was irradiated with lasers (850 and 940 nm) and dose (3.15 J/cm2) for 20 minutes per session, twice a week for 4 weeks. Knee joint tissues were stained and scanned using an in vivo micro-computed tomography (CT) scanner. Serum interleukin (IL)-6 and IL-18 levels were determined using enzyme-linked immuno-sorbent assay. Several functional tests (lines crossed, rotational movement, rearing, and latency to remain rotating rod) were performed 24 hours before LED treatment and at 7, 14, 21, and 28 days after treatment. RESULTS: LED-treated rats showed improved locomotor function and suppressed matrix-degrading cytokines. Micro-CT images indicated that LED therapy had a preserving effect on cartilage and cortical bone. CONCLUSION: LED treatment using wavelengths of 850 and 940 nm resulted in significant functional, anatomical, and histologic improvements without adverse events in a rat model. Further research is required to determine the optimal wavelength, duration, and combination method, which will maximize treatment effectiveness.

Effect of saline intrusion on rice production in the Mekong River Delta.

Saline intrusion is increasingly threatening the rice farming system in The Mekong River Delta (MRD). Identifying the impact of this disaster on rice farming and providing promptly adaptable solutions is an urgent issue. This study evaluates the influence of saline intrusion on rice productivity of households in the MRD. We utilize the quasi-experimental method, the difference-in-difference (DID) method, with farm level panel data on rice farming extracted from the Vietnam Household Living Standards Survey (VHLSS) in 2014 and 2016. The empirical results indicate that households affected by saline intrusion have lower total production and lower productivity compared to the unaffected group. The affected group has lower total revenue of approximately 4969.8 thousand VND per ha and lower net revenue, on an average of 4679.3 thousand VND per ha, compared to the comparable unaffected group. Among the subsamples of different regions, the damage magnitude of households in severely affected regions by salinity intrusion is higher than in less severely affected areas. Some policy implications that can be proposed from this research are that the management agency should continue to update information on weather and climate change scenarios for forecasting and timely information for rice farmers. The agency comprehensively evaluates the effectiveness of transformed models of sustainable agricultural production adapted to salinity intrusion and replicates high-effective production models; restructure rice cultivation following the salinity intrusion level of each locality.

Evaluation of Sensitive Urine DNA-Based PENK Methylation Test for Detecting Bladder Cancer in Patients with Hematuria.

Hematuria is a prevalent symptom associated with bladder cancer (BC). However, the invasiveness and cost of cystoscopy, the current gold standard for BC diagnosis in patients with hematuria, necessitate the development of a sensitive and accurate noninvasive test. This study introduces and validates a highly sensitive urine-based DNA methylation test. The test improves sensitivity in detecting PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR. In a case-control study comprising 175 patients with BC and 143 patients without BC with hematuria, the test's optimal cutoff value was determined by distinguishing between two groups, achieved an overall sensitivity of 86.9% and a specificity of 91.6%, with an area under the curve of 0.892. A prospective validation clinical study involving 366 patients with hematuria scheduled for cystoscopy assessed the test's performance. The test demonstrated an overall sensitivity of 84.2% in detecting 38 cases of BC, a specificity of 95.7%, and an area under the curve of 0.900. Notably, the sensitivity for detecting Ta high grade and higher stages of BC reached 92.3%. The test's negative predictive value was 98.2%, and the positive predictive value was 68.7%. These findings highlight the potential of the PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR test in urine as a promising molecular diagnostic tool for detecting primary BC in patients with hematuria, which may reduce the need for cystoscopy.

A Novel Incisionless Disposable Vaginal Device for Female Stress Urinary Incontinence: Efficacy and Quality of Life.

PURPOSE: This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence. METHODS: A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed. RESULTS: Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered. CONCLUSION: The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery. Trial Registration: The study was registered as a clinical trial (KCT0008369).

A Validation Study of a Deep Learning-Based Doping Drug Text Recognition System to Ensure Safe Drug Use among Athletes.

This study aimed to develop an English version of a doping drug-recognition system using deep learning-based optical character recognition (OCR) technology. A database of 336 banned substances was built based on the World Anti-Doping Agency's International Standard Prohibited List and the Korean Pharmaceutical Information Center's Drug Substance Information. For accuracy and validity analysis, 886 drug substance images, including 152 images of prescriptions and drug substance labels collected using data augmentation, were used. The developed hybrid system, based on the Tesseract OCR model, can be accessed by both a smartphone and website. A total of 5379 words were extracted, and the system showed character recognition errors regarding 91 words, showing high accuracy (98.3%). The system correctly classified all 624 images for acceptable substances, 218 images for banned substances, and incorrectly recognized 44 of the banned substances as acceptable. The validity analysis showed a high level of accuracy (0.95), sensitivity (1.00), and specificity (0.93), suggesting system validity. The system has the potential of allowing athletes who lack knowledge about doping to quickly and accurately check whether they are taking banned substances. It may also serve as an efficient option to support the development of a fair and healthy sports culture.

The effects of fluid absorption and plasma volume changes in athletes following consumption of various beverages.

BACKGROUND: To verify the hydration effects of oral rehydration solution (ORS) on athletes by comparing the degrees of fluid absorption and plasma volume changes following beverage consumption, including ORS. METHODS: Thirty-one participants visited the testing laboratory 4 times at 1-week intervals to consume 1 L of beverage (e.g., water, ORS, and two sports drinks [SpD]) for 30 min on each visit. The urine output was measured 4 times at 1 h, 2 h, 3 h, and 4 h after beverage consumption. A blood sample was collected 3 times at 1 h, 2 h, and 3 h after beverage consumption. Body weight was measured once in 4 h after beverage consumption. RESULTS: Body weight change was smaller for ORS than for water, SpD1, and SpD2 (p < 0.05). Cumulative urine output in 4 h was lower for ORS, SpD1, and SpD2 than for water (p < 0.05), and it was lower for ORS than for SpD2 (p < 0.05). BHI in 4 h was higher for ORS, SpD1, and SpD2 than for water (p < 0.05), and it was higher for ORS than for SpD2 (p < 0.05). There was no significant difference in PVC for different beverages at all test times, i.e.., 1 h, 2 h, and 3 h. CONCLUSIONS: We evaluated the hydration effects of the consumption of beverages, such as water, SpD, and ORS in athletes. ORS and SpD were more effective than water. A comparison between ORS and SpD showed that the result could vary depending on the type of SpD.

Transcriptomic Profiling Analysis of Castration-Resistant Prostate Cancer Cell Lines Treated with Chronic Intermittent Hypoxia.

Castration-resistant prostate cancer (CRPC) is still a major concern in men's health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the effect of hypoxia on prostate cancer, two and five cycles of hypoxia and reoxygenation were administered using 22Rv1 cell lines and denominated as 22Rv1-CI and 22Rv1-PCI, respectively. Cancer cell migration was promoted in 22Rv1-CI compared to controls, and the expression of COL13A1 was significantly up-regulated in 22Rv1-CI according to differentially expressed gene analysis of RNA sequencing among groups. Cancer cell migration was impeded in a wound healing assay after transfecting si-COL13A1. Moreover, the expression of COL13A1 was also higher in the cell line originating from bone metastatic prostate cancer compared to other cell lines. Using the open database GEO, we also confirmed that the expression of COL13A1 was higher in bone metastatic prostate cancer tissue than in localized prostate cancer tissue in patients. Therefore, COL13A1 may be closely related to the bony metastasis of prostate cancer, and our findings may provide valuable information on the pathophysiology of the metastatic niche induced by hypoxia in patients with CRPC.

Conditioned Medium of Human Pluripotent Stem Cell-Derived Neural Precursor Cells Exerts Neurorestorative Effects against Ischemic Stroke Model.

Previous studies have shown that early therapeutic events of neural precursor cells (NPCs) transplantation to animals with acute ischemic stroke readily protected neuronal cell damage and improved behavioral recovery through paracrine mechanisms. In this study, we tested the hypothesis that administration of conditioned medium from NPCs (NPC-CMs) could recapitulate the beneficial effects of cell transplantation. Rats with permanent middle cerebral artery occlusion (pMCAO) were randomly assigned to one of the following groups: PBS control, Vehicle (medium) controls, single (NPC-CM(S)) or multiple injections of NPC-CM(NPC-CM(M)) groups. A single intravenous injection of NPC-CM exhibited strong neuroregenerative potential to induce behavioral recovery, and multiple injections enhanced this activity further by suppressing inflammatory damage and inducing endogenous neurogenesis leading to histopathological and functional recovery. Proteome analysis of NPC-CM identified a number of proteins that are known to be associated with nervous system development, neurogenesis, and angiogenesis. In addition, transcriptome analysis revealed the importance of the inflammatory response during stroke recovery and some of the key hub genes in the interaction network were validated. Thus, our findings demonstrated that NPC-CM promoted functional recovery and reduced cerebral infarct and inflammation with enhanced endogenous neurogenesis, and the results highlighted the potency of NPC-CM in stroke therapy.

Combination therapy with tamsulosin and traditional herbal medicine for lower urinary tract symptoms due to benign prostatic hyperplasia: A double-blinded, randomized, pilot clinical trial.

OBJECTIVES: To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: A prospective, randomized, double-blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health-Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate-specific antigen were performed. RESULTS: In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub-score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs. CONCLUSION: Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add-on treatments in patients with storage symptoms with alpha-blocker monotherapy.

Metformin and Sildenafil Attenuate Inflammation and Suppress Apoptosis After Ischemia/Reperfusion Injuries in Rat Urinary Bladder.

PURPOSE: Although metformin and sildenafil can protect various organs against ischemia/reperfusion (I/R) injuries, their effects and mechanisms of action in bladder I/R injuries remain unknown. This study investigated the effects and mechanisms of action of metformin and sildenafil against bladder I/R insults in rats. METHODS: One hundred male Sprague-Dawley rats were randomly divided into 5 groups, each of which contained 20 rats: a sham-operated group, a bladder I/R group, and bladder I/R groups treated with metformin, sildenafil, or both agents. Ischemia was induced by clamping the bilateral common iliac arteries with atraumatic vascular clamps for 2 hours, followed by reperfusion for 7 days. During this period, rats were injected once daily with 4-mg/kg metformin and/or 1-mg/kg sildenafil. RESULTS: I/R injuries induced increased malondialdehyde levels and myeloperoxidase activity and decreased superoxide dismutase activity. These changes were attenuated by treatment with metformin and/or sildenafil. The I/R group had significantly higher Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), Bax, caspase-3, and nuclear factor-kappa B (NF-κB) levels, and lower extracellular signal-regulated kinase, and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment. No differences in the levels of these markers were observed between rats coadministered metformin and sildenafil and those treated with either agent alone. CONCLUSION: Metformin and sildenafil protected the rat bladder against I/R injuries. This effect may have been due to the inhibition of reactive oxygen species production through MAPK, Bax, and Bcl-2 activation, and the restoration of inflammation through NF-κB inhibition. However, the combination of metformin and sildenafil was not more effective than either agent alone.

Impact of Percutaneous Nephrostomy on the Efficacy of in Situ Shock Wave Lithotripsy for Upper Ureteral Stones.

PURPOSE: To investigate whether a Percutaneous nephrostomy (PCN) has any impact on the success rate of shock wave lithotripsy (SWL) and to estimate the probability of stone-free in SWL patients with upper ureter stones. MATERIALS AND METHODS: Overall, 236 patients who underwent SWL for upper ureter stones between 2015 and 2019 were evaluated. Forty-nine patients who underwent PCN during SWL were identified. Medical data of the patients were retrospectively reviewed, and possible prognostic features were evaluated. RESULTS: Out of all patients, 147 patients were selected through propensity score matching. There were no significant differences between the PCN and no PCN groups, except for a lower stone-free rate (55.1% vs. 74.5%, p = .018) and one-session success rate (24.5% vs. 50.0%, p = .003) in the PCN group. In univariate analysis, a younger age, the female sex, a smaller size of stone, lower mean stone density (MSD), and absence of PCN were positive predictive factors of being stone-free in patients who underwent SWL. In multivariate analysis, a smaller size, lower MSD, and absence of PCN were positive predictive factors of being stone-free in patients who underwent SWL. CONCLUSION: Stone size, MSD, and PCN were prognostic factors that influence the outcome of SWL. The presence of PCN during SWL is associated with adverse success rates in patients with upper ureter stones.

Extracellular Vesicles in Regenerative Medicine: Potentials and Challenges.

The ultimate goal of regenerative medicine is to regain or restore the damaged or lost function of tissues and organs. Several therapeutic strategies are currently being explored to achieve this goal. From the point of view of regenerative medicine, extracellular vesicles (EVs) are exceptionally attractive due to the fact that they can overcome the limitations faced by many cell therapies and can be engineered according to their purpose through various technical modifications. EVs are biological nanoscale vesicles naturally secreted by all forms of living organisms, including prokaryotes and eukaryotes, and act as vehicles of communication between cells and their surrounding environment. Over the past decade, EVs have emerged as a new therapeutic agent for various diseases and conditions owing to their multifaceted biological functions. This is reflected by the number of publications on this subject found in the Web of Science database, which currently exceeds 12,300, over 85% of which were published within the last decade, demonstrating the increasing global trends of this innovative field. The reviews collected in this special issue provide an overview of the different approaches being explored in the use of EVs for regenerative medicine.

Is PSA density of the peripheral zone as a useful predictor for prostate cancer in patients with gray zone PSA levels?

BACKGROUND: Serum prostate-specific antigen (PSA) is widely used in screening tests for prostate cancer. As the low specificity of PSA results in unnecessary and invasive prostate biopsies, we evaluated the clinical significance of various PSAs and PSA density (PSAD) related to peripheral zones in patients with gray zone PSA level (4-10 ng/mL). METHODS: A total of 1300 patients underwent transrectal ultrasonography-guided prostate biopsy from 2014 to 2019. Among them, 545 patients in the gray zone were divided into the prostate cancer diagnosis group and the non-prostate cancer diagnosis group, and PSA, relative extra transitional zone PSA (RETzPSA), estimated post holmium laser enucleation of the prostate PSA (EPHPSA), PSAD, peripheral zone PSA density (PZPSAD) and extra-transitional zone density (ETzD) were compared and analyzed using receiver-operating characteristics (ROC) analysis after 1:1 matching using propensity score. RESULTS: Area under the ROC curve values of PSA, EPHPSA, RETzPSA, PSA density, ETzD, and PZPSAD were 0.553 (95% CI: 0.495-0.610), 0.611 (95% CI: 0.554-0.666), 0.673 (95% CI: 0.617-0.725), 0.745 (95% CI: 0.693-0.793), 0.731 (95% CI: 0.677-0.780) and 0.677 (95% CI: 0.611-0.719), respectively. PSAD had 67.11% sensitivity, 71.71% specificity, and 70.34% positive predictive rate at 0.18 ng/mL/cc. ETzD had 69.08% sensitivity, 64.47% specificity, and 66.04% positive predictive rate at 0.04 ng/mL/cc. When the cut-off value of PSAD was increased to 0.18 ng/mL/cc, the best results were obtained with an odds ratio of 5.171 (95% CI: 3.171-8.432), followed by ETzD with 4.054 (95% CI: 2.513-6.540). CONCLUSIONS: These results suggested that volume-adjusted parameters (ETzD and PSAD) might be more sensitive and accurate than various PSA in gray zone patients who required prostate biopsy to reduce unnecessary biopsy.