Improved Outcomes Following a Conservative Approach to Hemodynamically Significant PDA: A Comparison Across Two Periods.

INTRODUCTION: Patent ductus arteriosus (PDA) is a commonly encountered morbidity that occurs inversely with gestational age. In response to the growing trend of avoiding PDA ligation and prophylactic interventions, our center adopted a conservative approach starting in September 2020. This approach involves more precise fluid restriction for hemodynamically significant (hs) PDA.This study aims to evaluate whether a conservative approach to hs PDA has led to a reduction in adverse clinical outcomes for very low birth weight infants (VLBWI) during the period of conservative treatment Methods: Since more conservative approach to hemodynamically significant (hs) PDA was adopted since September 2020, the two periods were divided as Period 1 (Jan 2015 to Aug 2020) and Period 2 (Sep 2020 to June 2023). Fluid therapy was carefully monitored and advanced from day 1 in all VLBWI and a more conservative approach as fluid restriction was attempted in hs PDA during Period 2. RESULTS: Of the 540 VLBWI with hs PDA, 348 infants were born and diagnosed with hs PDA. Period 2 demonstrated a significantly higher rate of medical treatment (79.17% vs 19.51%) and lower PDA ligation (54.17% vs 78.05%). Period 2 showed a greater adherence to conservative fluid restriction compared to Period 1.BPD and BPD ≥ moderate, sepsis, NEC (≥ grade 2), IVH (grade≥3) were notably lower in Period 2 with lower mortality. In regard to PDA related treatment, primary PDA ligation was significantly higher in Period 1.The secondary PDA ligation after medical failure and more conservative fluid restriction were significantly higher in Period 2. At corrected age of 18-24 months, cognitive score was significantly lower in VLBWI born in period 1 compared to those born in period 2. CONCLUSION: Our study demonstrated that a conservative approach to hs PDA led to better clinical outcomes and improved cognitive scores at a corrected age of 18-24 months compared to the period of active PDA ligation. This conservative strategy involving more precise fluid restriction and the judicious use of appropriate diuretics, has shown to improve clinical outcomes with minimal intervention.

Complement C5a Receptor Signaling in Macrophages Enhances Trained Immunity Through mTOR Pathway Activation.

Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies ß-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.

Muscle Advancement During Arthroscopic Rotator Cuff Repair as a Treatment Option for Irreparable Rotator Cuff Tears.

Background: The management of irreparable rotator cuff tears presents a surgical dilemma. However, supraspinatus muscle advancement (MA) could be used to convert irreparable to reparable tears without requiring a graft. Purpose: To compare the outcomes of patients with an irreparable tear who underwent rotator cuff repair with MA with those with a reparable large to massive cuff tear who underwent rotator cuff repair. Study Design: Cohort study; Level of evidence, 3. Methods: We enrolled 62 patients who underwent rotator cuff repair for a large to massive tear between January 2020 and May 2022. Among them, 29 patients underwent an MA procedure due to an inability to repair despite releases (MA group), whereas the other 33 patients did not require the procedure (NMA group). At 1 year postoperatively, follow-up assessments including magnetic resonance imaging were performed to evaluate group outcomes. Results: Despite there being more revision surgery cases and a poorer potential for cuff healing in the MA group, the retear rates in the MA and NMA groups were similar (31.0% vs 21.2%, respectively; P = .401), as were clinical outcomes, including the visual analog scale for pain (2.9 vs 1.9; P = .076), University of California, Los Angeles (27.0 vs 29.1; P = .185), Constant (70.1 vs 74.9; P = .063), and American Shoulder and Elbow Surgeons (74.5 vs 81.8; P = .168) scores. Postoperative muscle power during forward elevation was weaker in the MA group than in the NMA group (35.1 vs 45.8 N; P = .052), but external rotation power was comparable (49.3 vs 59.0 N; P = .121). Progress in fatty degeneration of the supraspinatus was not significantly different in the 2 groups (P = .43), although the MA group showed a nonsignificant decrease in supraspinatus atrophy (P = .092) due to the lateral shift produced by the procedure. Conclusion: The MA procedure for irreparable tears produced outcomes comparable with reparable tears, offering a valuable perspective on the efficiency of the procedure. The comparable but relatively high retear rates emphasize the need for further studies to compare with other treatment options for irreparable tears.

Effect of biologic therapies on quality of life in severe asthma: Findings from the PRISM study.

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except "cough," were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P < 0.05). The total scores and subscores of all domains of the QLQAKA, SAQ, and EQ-5D improved significantly 6 months after biologic therapy but not after conventional therapy. The total QLQAKA, SAQ, and EQ-5D scores improved after 6 months in the anti-IL-5 (P < 0.05) and anti-IL-4/IL-13 (P < 0.05) treatment groups with no significant difference between groups (P > 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

Extraperitoneal single-port robot-assisted radical prostatectomy: Short-term outcomes and technique description.

PURPOSE: We evaluated the feasibility, safety, and learning curve of extraperitoneal single-port robot-assisted radical prostatectomy (SP-RARP) and introduced innovative surgical techniques to maintain the instrument positions during the procedures. MATERIALS AND METHODS: A cohort of 100 patients underwent extraperitoneal SP-RARP at our institution from December 2021 to April 2023. The procedures were performed by an experienced urology surgeon utilizing two surgical techniques for dissecting the posterior aspect of the prostate-"changing instrument roles" and "using camera inversion"-to prevent positional shifts between the camera and instruments. RESULTS: The mean operation time for SP-RARP was 93.58 minutes, and the mean console time was 65.16 minutes. The mean estimated blood loss during the procedures was 109.30 mL. No cases necessitated conversion to multi-port robot, laparoscopy, or open surgery, and there were no major complications during the hospital stay or in the short-term follow-up. Early outcomes of post-radical prostatectomy indicated a biochemical recurrence rate of 4.0% over a mean follow-up duration of 6.40 months, with continence and potency recovery rates of 92.3% and 55.8%, respectively. Analysis of the learning curve showed no significant differences in operation time, console time, and positive surgical margin rates between the initial and latter 50 cases. CONCLUSIONS: Extraperitoneal SP-RARP is a feasible and safe option for the treatment of localized prostate cancer in skilled hands. Continued accrual of cases is essential for future comparisons of SP-RARP with multiport approaches.

Cannabidiol Alleviates Imiquimod-Induced Psoriasis by Inhibiting JAK2-STAT3 in a Mouse Model.

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown efficacy in treating psoriasis, a chronic inflammatory skin disease affecting 1-3% of the global population; however, the mechanisms remain unclear. This study investigated CBD's effects on imiquimod (IMQ)-induced psoriasis in mice, which were divided into five groups: Control, IMQ, Clobetasol, 0.01% CBD, and 0.1% CBD. After inducing psoriasis with IMQ, clobetasol or CBD was applied. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), with histopathological changes examined via hematoxylin and eosin staining. Gene expression of inflammatory markers (Il1b, Il6, Il12b, Il17a, Il22, and Tnf) was analyzed by RT-PCR, while protein levels of signal transducer and activator of transcription (STAT)3, P-STAT3, Janus kinase (JAK)2, and JAK3 were evaluated through western blot and immunohistochemistry. The results demonstrated that CBD significantly reduced PASI scores, epidermal thickness, keratosis, hyperproliferation, and inflammation. Moreover, CBD inhibited the IL-23 receptor-mediated JAK2-STAT3 signaling pathway, leading to the downregulation of Il1b, Il6, Il12b, Il17a, Il22, and Tnf expression. These findings suggest that CBD effectively alleviates psoriasis-like symptoms in mice and may serve as a promising therapeutic agent for psoriasis by targeting the JAK2-STAT3 pathway.

Complete genome sequence of candidate probiotic Limosilactobacillus fermentum KUFM407.

It has been reported that the administration of Limosilactobacillus fermentum alleviates diseases such as osteoporosis and colitis. In this study, we report the complete genome sequence of Limosilactobacillus fermentum KUFM407, a probiotic strain of LAB isolated from Korean traditional fermented food, Kimchi. Whole genome sequencing of L. fermentum KUFM407 was performed on the Illumina MiSeq and Oxford Nanopore MinION platform. The genome consisted of one circular chromosome (2,077,616 base pair [bp]) with a guanine cytosine (GC) content of 51.5% and one circular plasmid sequence (13,931 bp). Genome annotation identified 1,932 protein-coding genes, 15 rRNAs, and 58 tRNAs in the assembly. The function annotation of the predicted proteins revealed genes involved in the biosynthesis of bacteriocin and fatty acids. The complete genome of L. fermentum KUFM407 could provide valuable information for the development of new probiotic food and health supplements.

Comparison of Asthma Phenotypes in Severe Asthma Cohorts (SARP, U-BIOPRED, ProAR and COREA) From 4 Continents.

PURPOSE: Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively. METHODS: The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma. RESULTS: The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts. CONCLUSIONS: The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.

Pirfenidone Alleviates Inflammation and Fibrosis of Acute Respiratory Distress Syndrome by Modulating the Transforming Growth Factor-ß/Smad Signaling Pathway.

Acute respiratory distress syndrome (ARDS) occurs as an acute onset condition, and patients present with diffuse alveolar damage, refractory hypoxemia, and non-cardiac pulmonary edema. ARDS progresses through an initial exudative phase, an inflammatory phase, and a final fibrotic phase. Pirfenidone, a powerful anti-fibrotic agent, is known as an agent that inhibits the progression of fibrosis in idiopathic pulmonary fibrosis. In this study, we studied the treatment efficiency of pirfenidone on lipopolysaccharide (LPS) and bleomycin-induced ARDS using rats. The ARDS rat model was created by the intratracheal administration of 3 mg/kg LPS of and 3 mg/kg of bleomycin dissolved in 0.2 mL of normal saline. The pirfenidone treatment group was administered 100 or 200 mg/kg of pirfenidone dissolved in 0.5 mL distilled water orally 10 times every 2 days for 20 days. The administration of LPS and bleomycin intratracheally increased lung injury scores and significantly produced pro-inflammatory cytokines. ARDS induction increased the expressions of transforming growth factor (TGF)-ß1/Smad-2 signaling factors. Additionally, matrix metalloproteinase (MMP)-9/tissue inhibitor of metalloproteinase (TIMP)-1 imbalance occurred, resulting in enhanced fibrosis-related factors. Treatment with pirfenidone strongly suppressed the expressions of TGF-ß1/Smad-2 signaling factors and improved the imbalance of MMP-9/TIMP-1 compared to the untreated group. These effects led to a decrease in fibrosis factors and pro-inflammatory cytokines, promoting the recovery of damaged lung tissue. These results of this study showed that pirfenidone administration suppressed inflammation and fibrosis in the ARDS animal model. Therefore, pirfenidone can be considered a new early treatment for ARDS.

Deep learning-based prediction of Clostridioides difficile infection caused by antibiotics using longitudinal electronic health records.

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis. It is recognized as one of the most significant hospital-acquired infections. Although CDI can develop severe complications and spores of Clostridioides difficile can be transmitted by the fecal-oral route, CDI is occasionally overlooked in clinical settings. Thus, it is necessary to monitor high CDI risk groups, particularly those undergoing antibiotic treatment, to prevent complications and spread. We developed and validated a deep learning-based model to predict the occurrence of CDI within 28 days after starting antibiotic treatment using longitudinal electronic health records. For each patient, timelines of vital signs and laboratory tests with a 35-day monitoring period and a patient information vector consisting of age, sex, comorbidities, and medications were constructed. Our model achieved the prediction performance with an area under the receiver operating characteristic curve of 0.952 (95% CI: 0.932-0.973) in internal validation and 0.972 (95% CI: 0.968-0.975) in external validation. Platelet count and body temperature emerged as the most important features. The risk score, the output value of the model, exhibited a consistent increase in the CDI group, while the risk score in the non-CDI group either maintained its initial value or decreased. Using our CDI prediction model, high-risk patients requiring symptom monitoring can be identified. This could help reduce the underdiagnosis of CDI, thereby decreasing transmission and preventing complications.

Sex-specific survival gene mutations are discovered as clinical predictors of clear cell renal cell carcinoma.

Although sex differences have been reported in patients with clear cell renal cell carcinoma (ccRCC), biological sex has not received clinical attention and genetic differences between sexes are poorly understood. This study aims to identify sex-specific gene mutations and explore their clinical significance in ccRCC. We used data from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), The Renal Cell Cancer-European Union (RECA-EU) and Korean-KIRC. A total of 68 sex-related genes were selected from TCGA-KIRC through machine learning, and 23 sex-specific genes were identified through verification using the three databases. Survival differences according to sex were identified in nine genes (ACSS3, ALG13, ASXL3, BAP1, JADE3, KDM5C, KDM6A, NCOR1P1, and ZNF449). Female-specific survival differences were found in BAP1 in overall survival (OS) (TCGA-KIRC, p = 0.004; RECA-EU, p = 0.002; and Korean-KIRC, p = 0.003) and disease-free survival (DFS) (TCGA-KIRC, p = 0.001 and Korean-KIRC, p = 0.000004), and NCOR1P1 in DFS (TCGA-KIRC, p = 0.046 and RECA-EU, p = 0.00003). Male-specific survival differences were found in ASXL3 (OS, p = 0.017 in TCGA-KIRC; and OS, p = 0.005 in RECA-EU) and KDM5C (OS, p = 0.009 in RECA-EU; and DFS, p = 0.016 in Korean-KIRC). These results suggest that biological sex may be an important predictor and sex-specific tailored treatment may improve patient care in ccRCC.

Sargassum horneri extract fermented by Lactiplantibacillus pentosus SH803 mediates adipocyte metabolism in 3T3-L1 preadipocytes by regulating oxidative damage and inflammation.

Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1ß, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPß, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPß, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

Gut Dysbiosis in the First-Passed Meconium Microbiomes of Korean Preterm Infants Compared to Full-Term Neonates.

Since gestational age (GA) is an important factor influencing the presence of specific microbiomes, we aimed to characterize the core microbiomes of preterm infants compared to full-term (FT) infants. This study investigated the differences in microbiota composition between very preterm (VP), moderate-to-late preterm (MLP), and FT neonates by examining the core microbiomes of a large cohort of Korean neonates. Meconium samples from 310 neonates with a GA range of 22-40 weeks were collected, and 16S rRNA analyses were performed; 97 samples were obtained from the FT, 59 from the VP, and 154 from the MLP group. Firmicutes, Bacteroidetes, and Proteobacteria were the phylum-level core microbiomes. Infants born before 37 weeks showed a disruption in the core microbiomes. At the phylum level, the relative abundance of Bacteroidetes was positively (r = 0.177, p = 0.002) correlated with GA, while that of Proteobacteria was negatively (r = -0.116, p = 0.040) correlated with GA. At the genus level, the relative abundances of Bacteroides and Prevotella were positively correlated with GA (r = 0.157, p = 0.006; r = 0.160, p = 0.005). The meconium of preterm infants exhibited significantly lower α-diversities than that of FT infants. ß-diversities did not appear to differ between the groups. Overall, these findings underscore the importance of GA in shaping the early gut microbiome.

Development of a deep learning-based fully automated segmentation of rotator cuff muscles from clinical MR scans.

BACKGROUND: The fatty infiltration and atrophy in the muscle after a rotator cuff (RC) tear are important in surgical decision-making and are linked to poor clinical outcomes after rotator cuff repair. An accurate and reliable quantitative method should be developed to assess the entire RC muscles. PURPOSE: To develop a fully automated approach based on a deep neural network to segment RC muscles from clinical magnetic resonance imaging (MRI) scans. MATERIAL AND METHODS: In total, 94 shoulder MRI scans (mean age = 62.3 years) were utilized for the training and internal validation datasets, while an additional 20 MRI scans (mean age = 62.6 years) were collected from another institution for external validation. An orthopedic surgeon and a radiologist manually segmented muscles and bones as reference masks. Segmentation performance was evaluated using the Dice score, sensitivities, precision, and percent difference in muscle volume (%). In addition, the segmentation performance was assessed based on sex, age, and the presence of a RC tendon tear. RESULTS: The average Dice score, sensitivities, precision, and percentage difference in muscle volume of the developed algorithm were 0.920, 0.933, 0.912, and 4.58%, respectively, in external validation. There was no difference in the prediction of shoulder muscles, with the exception of teres minor, where significant prediction errors were observed (0.831, 0.854, 0.835, and 10.88%, respectively). The segmentation performance of the algorithm was generally unaffected by age, sex, and the presence of RC tears. CONCLUSION: We developed a fully automated deep neural network for RC muscle and bone segmentation with excellent performance from clinical MRI scans.

Enhanced Survival of 22-25 Week Preterm Infants After Proactive Care Implementation: A Comparative Analysis of Two Time Periods.

OBJECTIVES: To investigate the impact of proactive perinatal care on periviable preterm infants before and after its implementation. METHODS: This retrospective cohort study was conducted over a period of 10 y, from 2013 to 2019, referred to as Phase I, and from 2020 to 2022, referred to as Phase II. A total of 162 eligible infants born between 220/7 and 256/7 wk of gestation were included in this analysis. RESULTS: A total of 125 infants were born in phase I, and 37 infants in phase II received proactive care with minimal handling. The mortality decreased from 54.4% to 24.3% (P = 0.001). The composite outcomes of severe brain injury or death, sepsis or death and necrotizing enterocolitis or death were also improved with proactive care. Gestational age [adjusted odds ratio (aOR) 0.900; 95% confidence interval (CI), 0.836-0.970], air leak syndrome (aOR 4.958; 95% CI, 1.681-14.624), massive pulmonary hemorrhage (aOR 4.944; 95% CI, 2.055-11.893), and birth in phase II (aOR 0.324; 95% CI, 0.115-0.912) were independently associated with mortality. CONCLUSIONS: The implementation of proactive care with minimal handling resulted in an increased survival rate and a reduction in the combined morbidities between the two time periods. The provision of proactive perinatal care with minimal handling is crucial for improving both the survival rates and clinical outcomes of these vulnerable infants.

Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction.

PURPOSE: Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascular function, remains unclear. Our objectives are to (i) evaluate the effect of Li-ESWT (specifically radial type ESWT [rESWT]) on penile microvascular perfusion (PMP) in aging rats, (ii) elucidate a possible mechanism, and (iii) evaluate its impact on angiogenic and smooth muscle biomarkers in cavernosal tissue. MATERIALS AND METHODS: Male rats (n=9; 15-18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. Rats were euthanized at the end of the study and penile tissues were analyzed for angiogenic markers (vascular endothelial growth factor-A [VEGF-A], endothelial nitric oxide synthase [eNOS]) and smooth muscle content (α-actin) using immunostaining, Western blot, and quantitative polymerase chain reaction (qPCR). RESULTS: rESWT resulted in more than a 2-fold increase in PMP (from 68.5 arbitrary units; 163.7 AU). L-NAME injection produced a <40%-50% decrease (185.3 to 101.0 AU) in rESWT-induced PMP response. Immunostaining revealed increased α-actin, eNOS, and VEGF-A in the cavernosum and these findings were confirmed by qPCR and Western blot results. CONCLUSIONS: rESWT improved PMP, which may be mediated via increased VEGF expression, which stimulates the NO/cyclic guanosine monophosphate pathway, resulting in sustained PMP. rESWT devices could offer a safe, non-invasive treatment for age-related ED.

Discovery and Validation of Survival-Specific Genes in Papillary Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel.

PURPOSE: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. MATERIALS AND METHODS: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan-Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. RESULTS: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10-7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10-7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10-7 and DFS: p = 1.21 × 10-7) databases. CONCLUSIONS: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment.

The impact of sexual reproduction-induced vertical migration on the complexity of harmful algal blooms in Heterosigma akashiwo.

Vertical migration behaviour, which is integral to marine energy circulation, is a prevalent trait among marine organisms. However, the behaviour of phytoplankton, particularly beyond diel vertical migration (DVM), remain underexplored compared to groups like zooplankton. Through the lens of the harmful alga Heterosigma akashiwo, which exhibits active vertical migrations and unique fluctuating bloom dynamics, this study aimed to explore the ecological intricacies and diverse benefits of phytoplankton vertical migration behaviours. During the bloom period of H. akashiwo, we unexpectedly observed a dense concentration of cells at bottom layer during daytime. This phase coincided with the emergence of cells related to this species' sexual reproduction. Laboratory experiments further showed an elevated frequency of sexual reproduction in the cell populations that migrated to deeper depths compared to those at the surface. This finding implies a connection between dense bottom accumulation (BA) and the life cycle transitions of the species. This BA phase persisted for two days, after which the populations returned to their standard DVM behaviour, providing insight into the unique fluctuating bloom dynamics of H. akashiwo. Our study suggests that phytoplankton vertical migrations are not strictly dictated by DVM, revealing diverse vertical migration behaviours that may contribute to the complexity of harmful algal bloom patterns.