Gene set correlation enrichment analysis for interpreting and annotating gene expression profiles.

Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (DEG) list (or each of its DEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVID-19-related cells and patient samples, Gscore provided a means for studying how DEGs are implicated in COVID-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual DEGs, DEG lists, and genome-wide expression profiles based on existing biological knowledge.

Evidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-Analog Antiviral Drug in the Inhibition of I K(M) or I K(DR) and in the Stimulation of I MEP.

Remdesivir (RDV, GS-5734), a broad-spectrum antiviral drug in the class of nucleotide analogs, has been particularly tailored for treatment of coronavirus infections. However, to which extent RDV is able to modify various types of membrane ion currents remains largely uncertain. In this study, we hence intended to explore the possible perturbations of RDV on ionic currents endogenous in pituitary GH3 cells and Jurkat T-lymphocytes. The whole-cell current recordings of ours disclosed that upon membrane depolarization in GH3 cells the exposure to RDV concentration-dependently depressed the peak or late components of I K(DR) elicitation with effective IC50 values of 10.1 or 2.8 µM, respectively; meanwhile, the value of dissociation constant of RDV-induced blockage of I K(DR) on the basis of the first-order reaction was yielded to be 3.04 µM. Upon the existence of RDV, the steady-state inactivation curve of I K(DR) was established in the RDV presence; moreover, the recovery became slowed. However, RDV-induced blockage of I K(DR) failed to be overcome by further addition of either α,ß-methylene ATP or cyclopentyl-1,3-dipropylxanthine. The RDV addition also lessened the strength of M-type K+ current with the IC50 value of 2.5 µM. The magnitude of voltage hysteresis of I K(M) elicited by long-lasting triangular ramp pulse was diminished by adding RDV. Membrane electroporation-induced current in response to large hyperpolarization was enhanced, with an EC50 value of 5.8 µM. Likewise, in Jurkat T-lymphocytes, adding RDV declined I K(DR) amplitude concomitantly with the raised rate of current inactivation applied by step depolarization. Therefore, in terms of the RDV molecule, there appears to be an unintended activity of the prodrug on ion channels. Its inhibition of both I K(DR) and I K(M) occurring in a non-genomic fashion might provide additional but important mechanisms through which in vivo cellular functions are seriously perturbed.

Cranberries for Preventing Recurrent Urinary Tract Infections in Uncircumcised Boys.

Background • Highly concentrated cranberry juice has long been considered to have protective properties against urinary tract infections (UTIs), on the basis of its content of cranberry proanthocyanidins, with A-type interflavan bonds. Objective • This study intended to evaluate the benefits of a highly concentrated cranberry juice for the prevention of repeated episodes of UTI in uncircumcised boys. Design • The study was a randomized, controlled trial. Setting • The study took place at Taipei City Hospital, Renai and Zhongxing Branches (Taipei City, Taiwan). Participants • Participants were 55 uncircumcised boys and 12 circumcised boys, aged 6 to 18 y, with histories of uncomplicated UTI, who were patients at the hospital. Intervention • The uncircumcised boys were randomly divided into 2 groups: (1) group 1 (n = 28) took 4 oz (120 mL) daily of cranberry juice for 6 mo; and (2) group 2 (n = 27), the negative control group, drank a placebo juice for 6 months. The circumcised boys in group 3, a positive control group, also drank a placebo juice for 6 mo. Outcome Measures • The time to UTI (ie, to the appearance of symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence to the treatment, and adverse effects were assessed at monthly visits. Results • After 6 mo of a prophylactic treatment with cranberry juice, the incidence of bacteriuria, mainly Escherichia coli, as shown in urine cultures at ≥1 × 105, were 25% (7/28), 37% (10/27), and 33.3% (4/12) in groups 1, 2 and 3, respectively. The comparisons of the rate of prevention of a recurrence of UTI between group 1 and group 2 and between group 1 and group 3 showed that group 1 had fewer recurrent episodes of UTI. No children withdrew from the study. No adverse events or side effects were recorded. Conclusions • Cranberry juice may reduce the number of repeated episodes of UTI in uncircumcised boys and may have beneficial effects against the growth of Gram-negative bacterial pathogens. Its preventive benefits against UTI in the uncircumcised boys were even higher than those of circumcision for the circumcised boys.

Comparison of extracorporeal shock wave lithotripsy running models between outsourcing cooperation and rental cooperation conducted in Taiwan.

BACKGROUND/PURPOSE: We conducted a retrospective study to compare the cost and effectiveness between two different running models for extracorporeal shock wave lithotripsy (SWL), including the outsourcing cooperation model (OC) and the rental cooperation model (RC). METHODS: Between January 1999 and December 2005, we implemented OC for the SWL, and from January 2006 to October 2011, RC was utilized. With OC, the cooperative company provided a machine and shared a variable payment with the hospital, according to treatment sessions. With RC, the cooperative company provided a machine and received a fixed rent from the hospital. We calculated the cost of each treatment session, and evaluated the break-even point to estimate the lowest number of treatment sessions to make the balance between revenue and cost every month. Effectiveness parameters, including the stone-free rate, the retreatment rate, the rate of additional procedures and complications, were evaluated. RESULTS: Compared with OC there were significantly less treatment sessions for RC every month (42.6±7.8 vs. 36.8±6.5, p=0.01). The cost of each treatment session was significantly higher for OC than for RC (751.6±20.0 USD vs. 684.7±16.7 USD, p=0.01). The break-even point for the hospital was 27.5 treatment sessions/month for OC, when the hospital obtained 40% of the payment, and it could be reduced if the hospital got a greater percentage. The break-even point for the hospital was 27.3 treatment sessions/month for RC. No significant differences were noticed for the stone-free rate, the retreatment rate, the rate of additional procedures and complications. CONCLUSION: Our study revealed that RC had a lower cost for every treatment session, and fewer treatment sessions of SWL/month than OC. The study might provide a managerial implication for healthcare organization managers, when they face a situation of high price equipment investment.

Change in intraoperative rectal temperature influencing erectile dysfunction following transurethral resection of the prostate.

BACKGROUND/PURPOSE: In this study, we assessed the relationship between changes in intraoperative rectal temperature and erectile function in patients who have undergone transurethral resection of the prostate. METHODS: Eighty-six potential patients with benign prostatic hyperplasia-induced lower urinary tract symptoms were studied. Patients were divided into two groups: group 1-small prostates (<40 ml) and group 2-large prostates (≥ 40 ml), as determined by transrectal ultrasound measurement. The intraoperative rectal temperature was evaluated using a transrectal thermosensor and the differences between the highest intra- and preoperative temperatures were recorded. The erectile function at baseline, at three months and at one-year postoperatively was assessed using the International Index of Erectile Function-5 (IIEF-5) questionnaire. RESULTS: Intraoperative rectal temperature differences were 0.54 ± 0.24°C for group 1 (n=45) and 0.44 ± 0.20°C for group 2 (n=41), (p=0.04). The IIEF-5 scores for group1 and group 2 were, respectively, 20.9 ± 1.6 and 20.6 ± 1.6 at baseline (p=0.32), 17.3 ± 2.9 and 18.7 ± 3.2 (p=0.037) at 3 months, 17.9 ± 2.7 and 18.7 ± 3.0 (p=0.17) at 1 year postoperatively. The deterioration of erectile function at 3 months post-operatively was observed for both groups. The percentage of retrograde ejaculation between two groups was not significantly different (p=0.33) at 1 year postoperatively. CONCLUSION: Our study revealed that a higher intraoperative rectal temperature difference caused by transurethral resection of the prostate might affect the postoperative erectile function, particularly in patients with a small prostate.

Species and antimicrobial resistance of uropathogens isolated from patients with urinary catheter.

A large number of hospitalized patients have an indwelling urinary tract catheter (IUC) placed at some time during their hospital stay and may suffer from catheter-associated urinary tract infections, the leading cause of nosocomial infections. Here we investigated the prevalence of uropathogens associated with catheter-associated urinary tract infections and assessed the resistances of these pathogens to commonly prescribed antibiotics. In total, 2,997 urine samples were examined at a regional hospital in Taipei, Taiwan in 2004: 1,948 (65%) samples from hospitalized patients and 1,049 (35%) samples from outpatients. Patients with IUCs accounted for 1,381 samples (46%). Stratified analyses were used to calculate the age- and gender-adjusted odds ratio (OR) of antimicrobial resistance associated with the use of IUCs. Compared to the urine specimens of the patients without IUCs, those isolated from catheterized patients had a lower prevalence rate of Escherichia (E.) coli (23.4% vs 36.8%) and higher rates of resistant strains including Pseudomonas species (16.4% vs 8.6%) and rare gram-negative bacilli (5.8% vs 4.5%). Additionally, IUCs significantly increased the antimicrobial resistance of E. coli (OR 2.41-3.07), other species of Enterobacteriaceae (OR 1.57-2.38), and rare gram-negative bacilli (OR 2.41-5.21) to nearly all antibiotics tested, such as trimethoprim/sulfamethoxazole. Thus, IUCs increased the prevalence of urinary tract infections caused by some highly resistant pathogens. Moreover, IUCs were associated with the increased risk of concurrent resistance of Enterobacteriaceae. Clinicians are advised to exercise better management of urinary catheter in order to further reduce and control catheter-associated urinary tract infections in hospitals.

Age-specific prevalence rates of phimosis and circumcision in Taiwanese boys.

BACKGROUND/PURPOSE: To estimate the age-specific prevalence rates of phimosis and circumcision in an urban sample of Taiwanese boys. METHODS: A convenience sample of 1145 boys aged from 7 to 13 years was enrolled and cross-sectionally evaluated for preputial retractability and status of circumcision. Another convenience sample of 59 newborn male infants was enrolled from the infant room of a city municipal hospital. These infants were examined for preputial development at birth. RESULTS: None of the newborn male infants had a completely retractable prepuce (i.e. type 3). The prevalence rate of type 3 prepuce increased with age from 71.7% (95% confidence interval [CI], 66.5-75.5%) for boys aged 7 years to 72.4% (95% CI, 67.3-77.0%) for boys aged 10 years and 84.1% (95% CI, 79.6-88.0%) for boys aged 13 years. In contrast, the prevalence rate of type 1 prepuce decreased with age from 83.1% (95% CI, 71.0-91.6%) for newborn infants to 0.3% (95% CI, 0.0001-1.8%) for boys aged 13 years. On the other hand, the prevalence of circumcision slightly increased with age from 7.2% (95% CI, 5.3-10.8%) for boys aged 7 years to 8.7% (95% CI, 6.5-13.3%) for boys aged 13 years. CONCLUSION: Nonretractability of the prepuce was very common among the Taiwanese newborns. Among the school boys, the degree of preputial separation and exposure of glans increased with age and progressed even more rapidly in adolescence. Very few boys still suffered from unretractable prepuce by the age of 13.

Transurethral RollerLoop vapor resection of prostate for treatment of symptomatic benign prostatic hyperplasia: a 2-year follow-up study.

OBJECTIVE: We compared the 2-year safety and efficacy of two transurethral resection techniques-transurethral vapor resection of the prostate (TUVRP) and conventional loop transurethral resection of the prostate (TURP)-in the surgical management of benign prostatic hyperplasia. MATERIAL AND METHODS: Between August 1997 and September 2002, 441 patients underwent transurethral prostatectomy, either TUVRP (n = 221) or TURP (n = 220). TUVRP was performed using a "RollerLoop" resection loop. All patients were assessed preoperatively by means of International Prostate Symptom Score (IPSS), quality of life (QOL) score, prostate volume, peak urinary flow (Qmax) and post-void residual volume (PVR) measurements and a sexual function questionnaire. Patients were followed up for 3, 6, 12 and 24 months after surgery, and this was followed by a comparison of the incidences of sexual dysfunction, complications and re-treatment. RESULTS: After 2 years of follow-up, no differences were noted between the TUVRP and TURP groups with respect to average IPSS (p = 0.9), QOL scores (p = 0.56), Qmax (p = 0.89) or PVR (p = 0.55), as well as the incidences of bladder neck contracture or urethral stricture (p = 0.34), re-treatment (p = 0.49) or sexual dysfunction (p = 0.57). However, significant reductions in operative time (p = 0.005), decrease in serum hemoglobin levels (p < 0.001), catheterization time (p < 0.001), postoperative hospital stay (p < 0.001) and hospitalization costs (p < 0.001) were observed in the TUVRP group compared to the TURP group. CONCLUSION: Our results suggest that TUVRP provides equivalent safety and efficacy to TURP during a 2-year follow-up period, in which short-term advantages in perioperative morbidity and cost savings were also demonstrated.

Transurethral electrovapor resection versus standard transurethral resection treatment for a large prostate: a 2-year follow-up study conducted in Taiwan.

INTRODUCTION: Those patients featuring a large prostate and undergoing transurethral resection typically face a longer duration of surgery, they have a higher degree of hemorrhage and a higher irrigant volume required for the procedure, and they tend to reflect a higher incidence of morbidity than is the case for a small prostate. We report on the relative safety and efficacy of transurethral electrovapor resection of the prostate (TUVRP) as compared with standard transurethral resection of the prostate (TURP) for Taiwanese patients having a prostate size >50 ml. PATIENTS AND METHODS: Seventy-six symptomatic benign prostatic hyperplasia patients featuring a prostate size >50 ml were randomized and underwent either TUVRP using wedge loop or standard TURP. Perioperative parameters, treatment outcome, and adverse events associated with the surgical procedure are assessed herein. RESULTS: Mean operation time, changes in hemoglobin levels, resected prostate weight, perioperative irrigant volume needed, and incidences of recatheterizations and readmissions, all differed significantly when the two surgical procedures were compared. The average expense differences for the two procedures were impressive (p < 0.0001). No postoperative intergroup sexual dysfunction differences were noted. Clinical improvements following either TUVRP or TURP were significant and sustained for at least a period of 2 years. Intergroup comparison of International Prostate Symptom Score, quality of life, peak flow rate, and postvoid residual volume revealed no significant differences at 2 years (p = 0.45, 0.48, 0.12, and 0.29, respectively). The need for postoperative medical retreatment and/or reoperation did not differ significantly between the two groups (p = 0.62 and p = 0.56, respectively, at 6 months and p = 0.47 and p = 0.48, respectively, at 2 years). CONCLUSIONS: The TUVRP procedure offers advantages as regards a number of perioperative parameters when compared with the TURP procedure, and it seems that TUVRP might provide at least an equivalent treatment outcome as is the case for TURP.