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Micronuclei (MN) can form through many mechanisms, including the breakage of aberrant cytokinetic chromatin bridges. The frequent observation of MN in tumors suggests that they might not merely be passive elements but could instead play active roles in tumor progression. Here, we propose a mechanism through which the presence of micronuclei could induce specific phenotypic and functional changes in cells and increase the invasive potential of cancer cells. Through the integration of diverse in vitro imaging and molecular techniques supported by clinical samples from patients with prostate cancer (PCa) defined as high-risk by the D'Amico classification, we demonstrate that the resolution of chromosome bridges can result in the accumulation of Emerin and the formation of Emerin-rich MN. These structures are negative for Lamin A/C and positive for the Lamin-B receptor and Sec61β. MN can act as a protein sinks and result in the pauperization of Emerin from the nuclear envelope. The Emerin mislocalization phenotype is associated with a molecular signature that is correlated with a poor prognosis in PCa patients and is enriched in metastatic samples. Emerin mislocalization corresponds with increases in the migratory and invasive potential of tumor cells, especially in a collagen-rich microenvironment. Our study demonstrates that the mislocalization of Emerin to MN results in increased cell invasiveness, thereby worsening patient prognosis., (© 2024. The Author(s).)

Perovskite crystals-with their exceptional nonlinear optical properties, lasing and waveguiding capabilities-offer a promising platform for integrated photonic circuitry within the strong-coupling regime at room temperature. Here we demonstrate a versatile template-assisted method to efficiently fabricate large-scale waveguiding perovskite crystals of arbitrarily predefined geometry such as microwires, couplers and splitters. We non-resonantly stimulate a condensate of waveguided exciton-polaritons resulting in bright polariton lasing from the transverse interfaces and corners of our perovskite microstructures. Large blueshifts with excitation power and high mutual coherence between the different edge and corner lasing signals are detected in the far-field photoluminescence, implying that a spatially extended condensates of coherent polaritons has formed. The condensate polaritons are found to propagate over long distances in the wires from the excitation spot and can couple to neighbouring wires through large air gaps, making our platform promising for integrated polaritonic circuitry and on-chip optical devices with strong nonlinearities., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Evaluating outcomes of concurrent Cox-Maze procedures in elderly patients undergoing high-risk cardiac surgery., Mehods: We retrospectively identified patients aged over 70 years with Atrial Fibrillation (AF) from 2011 to 2017 who had two or more other cardiac procedures. They were subdivided into two groups: 1. Cox-Maze IV AF ablation. 2. No-Surgical AF treatment. A propensity match score was used to generate a homogeneous cohort and to eliminate confounding variables. Heart rhythm was assessed from Holter reports or 12-lead ECG. Follow-up data was collected through telephone consultations and medical records., Results: There were 239 patients. Median follow up was 61 months. 70 patients had Cox-Maze IV procedures (29.3%). Demographic, intra- and post-operative outcomes were similar between groups although duration of pre-operative AF was shorter in Cox-Maze group (p = 0.001). There was no significant 30-day mortality difference in propensity matched cohorts (n = 84. P = 0.078). Sinus rhythm at annual and latest follow-up was 84.9% and 80.0% respectively in Maze group - 160 patients (66.9%) were alive at long-term follow-up with good survival outcomes in Cox Maze group. There was a high proportion of patients in NYHA 1 status in Cox-Maze group. No differences observed in freedom from stroke (p = 0.80) or permanent pacemaker (p = 0.33) between the groups., Conclusions: Surgical ablation is beneficial in elderly patients undergoing high-risk surgery - promoting excellent long-term freedom from AF and symptomatic / prognostic benefits, without added risk. Therefore, surgical risk should not be reason to deny benefits of concomitant AF-ablation., Clinical Trial Registration: Not required., (© 2024. Crown.)

Background: A congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life., Aim: Our network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients., Methods: The network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases-Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon., Results: Surgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary., Conclusions: To improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research., (© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Buschke-Löwenstein tumor (BLT), also called giant condyloma acuminatum is a rare clinical manifestation caused by human papillomavirus (HPV), usually type 6 or 11 (90 %). The BLT is described as a tumor with localized aggressiveness, rather slow but destructive and invasive growth of surrounding tissues, benign histology, low metastatic potential, and a high tendency of recurrence. We present the case of a 55-year old non-immunocompetent man, with beige, cauliflower-like papillomae presented on glans penis and coronal sulcus which increased in size for a few weeks. The lesions were surgically removed, while maintaining negative surgical margins and good cosmetic outcomes., (© 2024 The Authors.)

Multi-parametric prostate MRI (mpMRI) is crucial for diagnosing, staging, and assessing treatment response in individuals with prostate cancer. Radiologists, through an accurate and standardized interpretation of mpMRI, stratify patients who may benefit from more invasive treatment or exclude patients who may be harmed by overtreatment. The integration of prostate MRI into the diagnostic pathway is anticipated to generate a substantial surge in the demand for high-quality mpMRI, estimated at approximately two million additional prostate MRI scans annually in Europe. In this review we examine the immediate impact on healthcare, particularly focusing on the workload and evolving roles of radiologists and urologists tasked with the interpretation of these reports and consequential decisions regarding prostate biopsies. We investigate important questions that influence how prostate MRI reports are handled. The discussion aims to provide insights into the collaboration needed for effective reporting.

Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.

Purpose: To synthetize the current scientific knowledge on the use of ultrasound of the male urethra for evaluation of urethral stricture disease. This review aims to provide a detailed description of the technical aspects of ultrasonography, and provides some indications on clinical applications of it, based on the evidence available from the selected prospective studies. Advantages and limitations of the technique are also provided., Methods: A comprehensive literature search was performed using the Medline and Cochrane databases on October 2022. The articles were searched using the keywords "sonourethrography", "urethral ultrasound", "urethral stricture" and "SUG". Only human studies and articles in English were included. Articles were screened by two reviewers (M.F. and K.M.)., Results: Our literature search reporting on the role of sonourethrography in evaluating urethral strictures resulted in selection of 17 studies, all prospective, even if of limited quality due to the small patients' number (varied from 28 to 113). Nine studies included patients with urethral stricture located in anterior urethra and eight studies included patients regardless of the stricture location. Final analysis was based on selected prospective studies, whose power was limited by the small patients' groups., Conclusion: Sonourethrography is a cost-effective and safe technique allowing for a dynamic and three-dimensional urethra assessment. Yet, because of its limited value in detecting posterior urethral strictures, the standard urethrography should remain the basic 'road-map' prior to surgery. It is an operator-dependent technique, which can provide detailed information on the length, location, and extent of spongiofibrosis without risks of exposure to ionizing radiation., (© 2024. The Author(s).)

Introduction: The study presents the initial outcomes of robot-assisted radical prostatectomies (RARPs) using the Versius robotic system in a urological centre with no prior robotic surgery experience., Material and Methods: A retrospective analysis of 58 RARPs was conducted, including patients' parameters as well as Versius system performance., Results: The study involved 58 patients (average age 66.9 years). Median preoperative prostate specific antigen (PSA) was 9.8 ng/ml, with 48% having ISUP grade group ≥ 3 on biopsy and 25.8% showing extraprostatic extension on MRI. Median blood loss was 437 ml, with complications (10.3% Clavien-Dindo grade II and 4 grade III cases). One conversion to open surgery occurred (0.58%). Final pathology revealed 46.5% extraprostatic disease, and 25.8% had positive margins. Post-surgery, 96.5% had undetectable PSA at 6 weeks. Continence rates were 89.7% at 6 weeks, increasing to 91.3% at 12 months. Median catheter duration was 7.9 days, and the hospital stay was 4.5 days. Console time averaged 150.9 minutes, with a median operative time of 213 minutes. The Versius system reported medium priority alarms in 24.1% of operations, including 1266 alarms related to robotic arm clashes and 43 instrument swaps. One bedside unit exchange occurred with no console or robotic system failures., Conclusions: The Versius robotic system can be successfully introduced in a urological centre without prior robotic surgery experience. Our setup and operating room positioning are effective, safe, and reproducible. We encountered and resolved surgical and technical challenges. Further follow-up studies are needed to assess the system's performance., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)

Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer and its pathogenesis is strongly associated with VHL-HIF-VEGF signaling. SHH ligand is the upstream SHH pathway regulator, while GLI1 is its major effector that stimulates as a transcription factor, i.a. expression of VEGFA gene. The aim of present study was to assess the prognostic significance of SHH, GLI1 and VEGFA immunoreactivity in KIRC tissues. The analysis included paired tumor and normal samples from 34 patients with KIRC. The immunoreactivity of SHH, GLI1 and VEGFA proteins was determined by immunohistochemical (IHC) renal tissues staining. The IHC staining results were assessed using the immunoreactive score (IRS) method which takes into account the number of cells showing a positive reaction and the intensity of the reaction. Increased GLI1 protein immunoreactivity was observed in KIRC tissues, especially in early-stage tumors, according to the TNM classification. Elevated expression of the VEGFA protein was noted primarily in high-grade KIRC samples according to the Fuhrman/WHO/ISUP scale. Moreover, a directly proportional correlation was observed between SHH and VEGFA immunoreactivity in TNM 3 + 4 and Fuhrman/ISUP/WHO 3 + 4 tumor tissues as well as in samples of patients with shorter survival. We also observed an association between shorter patient survival as well as increased and decreased immunoreactivity, of the VEGFA and GLI1, respectively. The aforementioned findings suggest that the expression pattern of SHH, GLI1 and VEGFA demonstrates prognostic potential in KIRC., (© 2023. The Author(s).)

Background and Objectives: Penile cancer is a rare neoplasm in developed countries with an incidence of 0.8/100,000 per male inhabitant. Despite the development of personalized medicine and multimodal treatment, the outcome of penile cancer treatment is insufficient. Our study aimed to assess the levels of pro-inflammatory cytokines' mRNA such as interleukin 1-A (encoded by IL1A gene, alias IL-1A) , interleukin 1-B ( IL1B , IL-1B ), interleukin 1 receptor antagonist ( IL1RN , IL-1RN ), interleukin 6 ( IL6 , IL-6 ), transforming growth factor β1 ( TGFB1 , TGFβ-1 ), and Interferon-gamma ( INFG , INF-γ ) in penile cancer tissue and associate them with tumor progression and patient survival. Material and Methods: Skin biopsies from patients suffering from penile cancer (n = 6) and unchanged foreskin from 13 healthy adult males undergoing circumcision due to a short frenulum were obtained. Pro-inflammatory cytokine mRNA levels were quantified through qPCR. Results: We observed higher expression of pro-inflammatory cytokine genes (IL-1A, IL-1B, IL-6, INF-γ, TGF-β) in penile cancer tissue. The average follow-up period was 48 months (range: 38-54 months), during which only one penile tumor progression was observed However, this was without association with the nature of tumor (patient refused radical treatment). Conclusions: This is the first study to show increased expression of cytokines such as IL-1A, IL-1B, IL-6, INF-γ, and TGF-β in penile cancer with positive correlation between TNM staging and INF-γ levels in tumor samples (rs = 0.672, p = 0.045), which may be associated with the immunosuppressive role of the tumor environment.

Background: Multiparametric prostate MRI (mpMRI) is gaining wider recommendations for diagnosing and following up on prostate cancer. However, despite the high accuracy of mpMRI, false positive and false negative results are reported. Some of these may be related to normal anatomic structures, benign lesions that may mimic cancer, or poor-quality images that hamper interpretation. The aim of this review is to discuss common potential pitfalls in the interpretation of mpMRI., Methods: mpMRI of the prostates was performed on 3T MRI scanners (Philips Achieva or Siemens Magnetom Vida) according to European Society of Urogenital Radiology (ESUR) guidelines and technical requirements., Results: This pictorial review discusses normal anatomical structures such as the anterior fibromuscular stroma, periprostatic venous plexus, central zone, and benign conditions such as benign prostate hyperplasia (BPH), post-biopsy hemorrhage, prostatitis, and abscess that may imitate prostate cancer, as well as the appearance of prostate cancer occurring in these locations. Furthermore, suggestions on how to avoid these pitfalls are provided, and the impact of image quality is also discussed., Conclusions: In an era of accelerating prostate mpMRI and high demand for high-quality interpretation of the scans, radiologists should be aware of these potential pitfalls to improve their diagnostic accuracy.

Background: Airway management in life-threatening emergencies is essential for children, and endotracheal intubation is the gold standard. It protects against regurgitation and enables mechanical ventilation. New types of airway management equipment are being developed and implemented to meet the needs of medical personnel., Research Design and Methods: This prospective, randomized, cross-over simulation trial evaluated the success of endotracheal intubation in three scenarios: normal airway (scenario-A), tongue edema (scenario-B), and continuous chest compression (scenario-C), using the bébé Vie Scope™ laryngoscope (VieScope) and the Macintosh blade laryngoscope (MAC) as a comparative tool performed by nurses with limited tracheal intubation experience., Results: The results of the study showed that in scenario-A, there were no significant differences in the first attempt success rate or endotracheal intubation time between VieScope and MAC. However, VieScope was associated with better visualization of the glottis. In scenarios B and C, VieScope was significantly more effective than MAC in terms of first-pass success rate, time to intubate, Cormack-Lehane grade, POGO score, and ease of endotracheal intubation., Conclusions: Bébé VieScope may be useful for endotracheal intubation in pediatric patients, particularly in cases of tongue edema and ongoing chest compression, providing a higher first-pass success rate than conventional laryngoscopes.

Onco-nephrology is a new field of medicine which combines many aspects of kidney injury in cancer patients and cancers in patients with kidney disease. This connection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, numerous paraneoplastic syndromes and an increased rate cancers in dialysis and transplanted patients. The appropriate laboratory assessment of the kidney function allows to optimize chemotherapy and thus minimizes the risk of complications. This article focuses on acute kidney injury (AKI), chronic kidney disease (CKD), various electrolyte and acid-base disorders, the most common cancers after kidney transplantation and the kidney disorders associated with HSCT (hematopoietic stem cell transplantation). The possibility of the application of novel cancer therapy, such as cancer immunotherapy and proton therapy in transplant recipients was also discussed.

Introduction and Objective: In COVID-19, the rapid prediction of the severity of a patient's condition using modern biomarkers can accelerate the implementation of appropriate therapy, and thus improve the patient's prognosis., Material and Methods: A meta-analysis was conducted of data available in the literature on the differences in baseline suPAR blood concentration between patients (1) who tested positive and negative for COVID-19, (2) who had severe and non-severe COVID-19, and (3) COVID-19 survivors and non-survivors., Results: SuPAR levels in SARS-CoV-2 negative and positive patients varied and amounted to 3.61±1.59 ng/ml vs. 6.45±3.13 ng/ml, respectively (MD = -3.18; 95%CI: -4.71 to -1.66; p<0.001). suPAR levels among non-severe and severe COVID-19 patients were 7.06±2.64 ng/ml and 5.06±3.16 ng/ml (MD = 0.18; 95%CI: -2.48 to 2.83; p=0.90), respectively. Pooled analysis showed that suPAR levels between severe versus critical COVID-19 patients to be 5.59±1.54 ng/ml and 6.49±1.43 ng/ml, respectively (MD = -1.00; 95%CI: -1.31 to -0.70; p<0.001). The suPAR levels between ICU survivors versus non-survivors amounted to 5.82±2.33 ng/ml and 8.43±4.66 ng/ml (MD = -3.59; 95%CI: -6.19 to -1.00; p=0.007). In the case of in-hospital mortality, the mean suPAR level among survivors to hospital discharge was 5.63±1.27 ng/ml, compared to 7.85±2.61 ng/ml for patients who did not survive (MD = -3.58; 95%CI: -5.42 to -1.74; p<0.001)., Conclusions: SuPAR levels are significantly elevated in severe COVID-19 illness and maybe useful in predicting mortality. Further studies are needed to determine cut-off points and clarify the association of suPAR levels with disease progression. This is of utmost importance given the ongoing pandemic and overburdened health care systems.

Background: The study was undertaken to compare the diagnostic performance of diffusion kurtosis imaging (DKI) with the standard monoexponential (ME) apparent diffusion coefficient (ADC) model in the detection of significant prostate cancer (PCa), using whole-mount histopathology of radical prostatectomy specimens as a reference standard., Methods: 155 patients with prostate cancer had undergone multiparametric magnetic resonance imaging (mpMRI) at 3T before prostatectomy. Quantitative diffusion parameters-the apparent diffusion coefficient corrected for non-Gaussian behavior (D app ), kurtosis (K), ADC 1200 , and ADC 2000 were correlated with Gleason score and compared between cancerous and benign tissue and between GS ≤ 3 + 3 and GS ≥ 3 + 4 tumors., Results: The mean values of all diffusion parameters (D app , K, ADC 1200 , ADC 2000 ) were significantly different both between malignant and benign tissue and between GS ≤ 3 + 3 and GS ≥ 3 + 4 tumors. Although the kurtosis model was better fitted to DWI data, the diagnostic performance in receiver operating characteristic (ROC) analysis of DKI and the standard ADC model in the detection of significant PCa was similar in the peripheral zone (PZ) and in peripheral and transitional zones (TZ) together. In conclusion, our study was not able to demonstrate a clear superiority of the kurtosis model over standard ADC in the diagnosis of significant PCa in PZ and in both zones combined.

Background: The nuclear factor-κB transcription factors 1 and 2 (NFKB1 and NFKB2) are key components of the NF-κB pathway, which responds to inflammatory signals. Since the NFKB1/2 factors are activated via different inflammatory molecules, we aimed to check their expression levels in penile cancer (PC), penile dermatoses: lichen sclerosus (PLS) and zoon balanitis (ZB)., Methods: Skin biopsies from altered and healthy looking foreskin were obtained from 59 (49 LS; early PLS: 13, moderate PLS: 32, severe PLS: 4; 6 PC; 4 ZB) and unchanged foreskin from 13 healthy control adult males undergoing circumcision. NFKB1/2 mRNA levels were quantified by qPCR., Results: The highest levels of NFKB1 and NFKB2 were observed in PC, ca. 22 and 3.5 times higher than in control, respectively. NFKB1 expression was correlated with PLS progression (rs = 0.667) and was ca. 20 times higher in advanced PLS than in controls and early PLS. Occurrence of micro-incontinence was associated with elevated NFKB1 levels in PLS., Conclusion: This is the first study regarding gene profiles of NFKB1/2 in PC and penile dermatoses. New drugs targeting modulation of canonical-activated NF-κB pathway should be studied and introduced to the treatment of PLS and PC apart from other treatments.

Cystatin C is a specific biomarker of kidney function. We perform this meta-analysis to determine the association of Cystatin C with the COVID-19 severity. In this systematic review and meta-analysis, we searched PubMed, EMBASE, Cochrane library, and Web of Science for studies published until 2nd September 2022 that reported associations between Cystatin C levels and COVID-19 severity. The analysis was performed using a random-effects model to calculate pooled standard mean difference (SMD). Twenty-five studies were included in the meta-analysis. Pooled analysis showed statistically significant differences of Cystatin C levels among survive vs. decreased patients (0.998 ± 0.225 vs. 1.328 ± 0.475 mg/dL, respectively; SMD = -2.14; 95%CI: -3.28 to -1.01; p < 0.001). Cystatin C levels in COVID-19 severe vs. non-severe groups varied and amounted to 1.485 ± 1.191 vs. 1.014 ± 0.601 mg/dL, respectively (SMD = 1.81; 95%CI: 1.29 to 2.32; p < 0.001). Additionally, pooled analysis showed that Cystatin C levels in patients with acute kidney injury (AKI) was 1.562 ± 0.885 mg/dL, compared to 0.811 ± 0.108 mg/dL for patients without AKI (SMD = 4.56; 95%CI: 0.27 to 8.85; p = 0.04). Summing up, Cystatin C is a potentially very good marker to be used in the context of COVID-19 disease due to the prognosis of patients' serious condition, risk of AKI and mortality. In addition, Cystatin C could be used as a marker of renal complications in COVID-19 other than AKI due to the need to monitor patients even longer after leaving the hospital.

The SARS-CoV-2 (COVID-19) pandemic is a major issue that necessitates the use of cutting-edge disease prediction models. The aim of the study was to assess the existing evidence regarding association between Krebs von den Lungen-6 levels and COVID-19 severity. A literature search was performed on Web of Science, PubMed, Scopus and Cochrane Central Register of Controlled Trials databases from 1 January 2020 up to 2 August 2022. The electronic database search was supplemented by searching Google Scholar. In addition, reference lists of relative articles were also reviewed. KL-6 levels among COVID-19 positive vs. negative patients varied and amounted to 443.37 ± 249.33 vs. 205.73 ± 86.8 U/mL (MD = 275.33; 95%CI: 144.57 to 406.09; p < 0.001). The KL-6 level was 402.82 ± 261.16 U/mL in the severe group and was statistically significantly higher than in the non-severe group (297.38 ± 90.46 U/mL; MD = 192.45; 95%CI: 118.19 to 266.72; p < 0.001). The KL-6 level in the mild group was 272.28 ± 95.42 U/mL, compared to 268.04 ± 55.04 U/mL in the moderate COVID-19 group (MD = −12.58; 95%CI: −21.59 to −3.57; p = 0.006). Our meta-analysis indicates a significant association between increased KL-6 levels and SARS-CoV-2 infection. Moreover, KL-6 levels are significantly higher in patients with a more severe course of COVID-19, indicating that KL-6 may be a useful predictor to identify patients at risk for severe COVID-19.

Background: Lower extremity peripheral artery disease is a problem of contemporary medicine and along with the ischemic heart disease it is considered to be a civilization disease. The risk of the disease increases significantly within a group of people reaching the age of 55 years and is closely related to co-occurring hazardous factors, such as diabetes, hyperlipidemia, hypertension or tobacco smoking. The first symptom reported by patients is intermittent claudication. Such symptoms may indicate that lower extremity peripheral artery disease does have an impact on posture disorders and motor skills., Methods: The study covered four stages. The first stage involved medical interviews to obtain information regarding anthropometry, age, motor organ surgery, concomitant diseases and the lifestyle. In the following stage the value of the ankle brachial index for both lower limbs were calculated. In case of symptomatic patients, additionally, the location of artery stenosis/aortoiliac section, was verified. The third stage involved using a dynamometric platform for determination of the body mass center position for both studied groups. In the fourth stage a treadmill walk test was used to assess the participants for intermittent claudication., Findings: Based on the obtained results, an attempt was taken to observe the relationship between the clinical characteristics of the disease and the body mass center position deviations., Interpretation: The attempt was undertaken to assess whether the measurement of body mass center position might be a diagnostic parameter to evaluate the patient's condition and thus an indication for taking a decision for surgical treatment or rehabilitation., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [ 68 Ga]Ga-PSMA PET/CT prior to surgery, with special consideration of PET-negative cases., Methods: The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [ 68 Ga]Ga-PSMA I&T PET/CT as part of the diagnostic work-up prior to radical prostatectomy. All primary tumors were routinely stained with H&E. In addition, immunohistochemical staining of PSMA was performed and the immunoreactive score (IRS) was computed as semiquantitative measure. Subsequently, imaging findings were correlated to histopathologic results., Results: Eighty-three percent (33/40) of patients presented focal uptake of [ 68 Ga]Ga-PSMA I&T in the primary tumor in at least one prostate lobe. Among PSMA-PET positive patients, one-third had lymph node metastases (LNM) detected by post-operative histopathology, while in PET negative patients, only 1 out of 7 presented with regional LN involvement; PSMA-avid distant lesions, predominantly in bones, were observed in 15% and 0% of patients, respectively. The median IRS classification of PSMA expression in tumor tissue was 2 (range, 1-3) both in PSMA-PET positive and negative prostate lobes, with significantly different interquartile range: 2-3 vs. 2-2, respectively (p = 0.03). The median volume of PSMA-PET positive tumors was 5.4 mL (0.2-32.9) as compared to 1.6 mL (0.3-18.3) of PET-negative tumors (p < 0.001). There was a significant but weak correlation between SUV max and percentage of PSMA-positive tumor cells (r = 0.46, p < 0.001). A total of 35/44 (~80%) lobes were positive in PSMA-PET imaging, when a cut-off percentage of PSMA-positive cells was ≥ 90%, while 19/36 (~53%) lobes with < 90% PSMA-positive cells were PSMA-PET negative., Conclusion: Positive [ 68 Ga]Ga-PSMA I&T PET/CT scan of primary tumor of PCa results from a combination of factors, such as homogeneity and intensity of PSMA expression, tumor volume and grade, with a cutoff value of ≥ 90% PSMA-positive cells strongly determining PET-positivity. Focal accumulation of [ 68 Ga]Ga-PSMA in the primary tumor may correlate positively with aggressiveness of prostate cancer, harboring higher risk of regional LN involvement and distant metastatic spread., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Renal cell carcinoma (RCC) is a disease with no specific diagnostic method or treatment. Thus, the evaluation of novel diagnostic tools or treatment possibilities is essential. In this study, a multiplatform untargeted metabolomics analysis of urine was applied to search for a metabolic pattern specific for RCC, which could enable comprehensive assessment of its biochemical background. Thirty patients with diagnosed RCC and 29 healthy volunteers were involved in the first stage of the study. Initially, the utility of the application of the selected approach was checked for RCC with no differentiation for cancer subtypes. In the second stage, this approach was used to study clear cell renal cell carcinoma (ccRCC) in 38 ccRCC patients and 38 healthy volunteers. Three complementary analytical platforms were used: reversed-phase liquid chromatography coupled with time-of-flight mass spectrometry (RP-HPLC-TOF/MS), capillary electrophoresis coupled with time-of-flight mass spectrometry (CE-TOF/MS), and gas chromatography triple quadrupole mass spectrometry (GC-QqQ/MS). As a result of urine sample analyses, two panels of metabolites specific for RCC and ccRCC were selected. Disruptions in amino acid, lipid, purine, and pyrimidine metabolism, the TCA cycle and energetic processes were observed. The most interesting differences were observed for modified nucleosides. This is the first time that the levels of these compounds were found to be changed in RCC and ccRCC patients, providing a framework for further studies. Moreover, the application of the CE-MS technique enabled the determination of statistically significant changes in symmetric dimethylarginine (SDMA) in RCC., Competing Interests: The authors declare that there are no conflicts of interest., (© 2022 The Author(s).)

Reservoirs of dense atomic gas (primarily hydrogen) contain approximately 90 per cent of the neutral gas at a redshift of 3, and contribute to between 2 and 3 per cent of the total baryons in the Universe 1-4 . These 'damped Lyman α systems'-so called because they absorb Lyman α photons within and from background sources-have been studied for decades, but only through absorption lines present in the spectra of background quasars and γ-ray bursts 5-10 . Such pencil beams do not constrain the physical extent of the systems. Here we report integral-field spectroscopy of a bright, gravitationally lensed galaxy at a redshift of 2.7 with two foreground damped Lyman α systems. These systems are greater than 238 kiloparsecs squared in extent, with column densities of neutral hydrogen varying by more than an order of magnitude on scales of less than 3 kiloparsecs. The mean column densities are between 10 20.46 and 10 20.84  centimetres squared and the total masses are greater than 5.5 × 10 8 -1.4 × 10 9 times the mass of the Sun, showing that they contain the necessary fuel for the next generation of star formation, consistent with relatively massive, low-luminosity primeval galaxies at redshifts greater than 2., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear., Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk., Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019., Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455)., Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation., Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75])., Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year., Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, with high mortality rates worldwide. The sonic hedgehog (SHH) molecular cascade is altered in various malignancies in tumorigenesis, and several SHH pathway inhibitors have been considered as potential anticancer drugs. The aim of the present study was to determine the expression profile of SHH signaling components and their target genes in ccRCC. Additionally, the present study examined the effects of SHH pathway inhibitory drugs (RU‑SKI43, cyclopamine and GLI‑antagonist 61) on cell viability, cell cycle progression, expression levels of SHH target genes and migration ability in 786‑O, ACHN and HK2 cells. The study also included paired tumor and normal samples from 62 patients with ccRCC. The mRNA levels in clinical samples and cell lines were measured via reverse transcription‑quantitative PCR. Cell viability was examined using a sulforhodamine B assay. Flow cytometry was used to investigate cell cycle progression and the migratory rate of cells was assessed using a wound healing assay. High mRNA levels of SHH , smoothened ( SMO ), glioma‑associated zinc finger protein ( GLI ) 1‑3 , BCL2 apoptosis regulator ( BCL2 ), MYC proto‑oncogene ( MYC ), vascular endothelial growth factor A ( VEGFA ) and cyclin D1 ( CCND1 ) were observed in the tumor tissues, especially in early ccRCC, according to the TNM stage or World Health Organization/International Society of Urological Pathology (ISUP) grade. High expression levels of VEGFA , as well as low CCND1 mRNA expression, were associated with short overall survival, and increased VEGFA expression was an independent prognostic factor of a poor outcome in patients with advanced ISUP grade (Cox hazard ratio test). Cyclopamine treatment was found to arrest 786‑O cells in the G 2 /M phase and decreased the expression levels of GLI1 , BCL2 , VEGFA and CCND1 . RU‑SKI43 inhibited cell migration and decreased the expression levels of BCL2 , MYC and CCND1 in ACHN cells. Overall, the results of the present study suggested that SHH signaling may be involved in the early development of ccRCC, and the expression levels of CCND1 and VEGFA may serve as prognostic factors of this disease. Cyclopamine and RU‑SKI43 appear to be potential anti‑renal cell carcinoma drugs; however, this hypothesis requires verification by further in vivo studies.

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups., Competing Interests: J.P.D. is cofounder and shareholder in Cray Innovation AB. The remaining authors have declared that no competing interests exist.

Purpose: To assess the expression of selected cytokines in penile lichen sclerosus (PLS) and associate them with the occurrence of micro-incontinence (MI) in different stages of PLS., Methods: The skin biopsies from 49 PLS affected, and 13 from nonlesional foreskins (healthy control adult males undergoing circumcision due to phimosis caused by short frenulum) were obtained. All specimens were used for RNA extraction and RT-qPCR. Quantitative assessment of the gene expression of interleukin 1-A (IL-1A), interleukin 1-B (IL-1B), interleukin 1 receptor antagonist (IL-1RN), interleukin 6 (IL-6), transforming growth factor β1 (TGF-β1), and interferon-gamma (INF-γ) was performed. To determinate the presence of MI, the patients were asked about voiding patterns, especially leaking tiny drops of urine from the urethral meatus after urination., Results: IL-1A, IL-6, and INF-γ mRNA levels were approximately 150, 16, and 59 times higher in PLS than in control samples, respectively. The highest IL-1A mRNA levels were observed in early PLS (n = 13), INF-γ in moderate PLS (n = 32), while IL-6 in severe PLS (n = 4). MI was noted in 45 PLS patients vs. 0 in control (p < 0.0001). IL-1A and IL-6 vs control ratios were concentration (ca.) 400 and 30 times higher, respectively, in MI PLS samples than in PLS without MI., Conclusion: Occlusion and irritating urine effect are associated with the clinical progression of penile LS with increased mRNA expression of IL-1A, INF-γ, and IL-6 pro-inflammatory cytokines in the foreskin., (© 2022. The Author(s).)

Introduction and Hypothesis: Surgical treatment using the mid-urethral tape has become a gold standard in the treatment of stress urinary incontinence in women. Many urogynecologists use ultrasound during the postoperative follow-up. The aim of this study was to investigate whether the position of the tape in the mid- or distal-urethra could influence the subjective assessment after surgery in 1-month control based on questionnaires of genitourinary symptoms, UDI6-SF and VAS scale., Methods: A group of 76 patients using a synthetic tension-free retropubic vaginal tape after anti-incontinence surgery was retrospectively included in this study. In a postoperative follow-up, the synthetic tape detection was performed using introital ultrasound, and its position was determined as a quotient T/U (T = distance between the external urethral orifice and the lower edge of the tape, U = urethral length). The patients were divided into two groups of 38 patients: one group with the position of the tape in the distal urethra (T/U ≤ 0.24) and the other group with the tape localised in the mid-urethra (T/U = 0.25-0.37). The correlation between the height of the tape position and the subjective assessment was evaluated in both groups of patients in the 1-month control., Results: No association was found between the height of the tape position in a group of patients after anti-incontinence surgery with a T/U value not exceeding 0.375 and the subjective assessment or the value of Vres., Conclusions: The height of the tape position, with the T/U not exceeding 0.375, has no impact on the subjective assessment of the surgical anti-incontinence treatment in 1-month control., (© 2022. The Author(s).)

The simultaneous determination of metabolites from biological fluids may provide more accurate information about the current body condition. So far, the metabolomics approach has been successfully applied to study the mechanism of several disorders and to search for novel biomarkers. Urine and plasma are widely accepted matrices for the evaluation of several pathologies, while prostate cancer (CaP) development is still unknown. For this reason, an alternative matrix, the seminal fluid, was proposed to expand the knowledge about the CaP pathomechanism. The main aim of this study was to develop and optimize the sample preparation protocol to ensure the highest coverage of the metabolome of ejaculate samples. Parameters like the type and composition of the solvent mixture, time of extraction, and applied volume of the solvent were tested. The optimized method was applied for the untargeted metabolomics profiling of seminal fluid samples obtained from CaP patients. Moreover, urine and serum samples were also prepared for untargeted metabolomics analysis. Analyses were carried out with the use of two complementary analytical techniques: GC-EI-QqQ/MS and LC-ESI-TOF/MS. Finally, the metabolic signature of seminal fluid (n = 7), urine (n = 7), and plasma (n = 7) samples was compared. Furthermore, the hypothesis of the increased level of metabolites in ejaculate samples related to the CaP development was evaluated. The results indicated that the developed and optimized sample preparation protocol for seminal fluid may be successfully applied for metabolomics study. Untargeted analysis of ejaculate enabled to determine the following classes of compounds: fatty acids, sphingolipids, phospholipids, sugars, and their derivatives, as well as amino acids. Finally, a comparison of the three tested matrices was carried out. To our best knowledge, it is the first time when the metabolic profile of the three matrices, namely, urine, plasma, and seminal fluid, was compared. Based on the results, it can be pointed out that ejaculate comprises the metabolic signature of both matrices (polar compounds characteristic for urine, and non-polar ones present in plasma samples). Compared to plasma, semen samples revealed to have a similar profile; however, determined levels of metabolites were lower in case of ejaculate. In case of urine samples, compared to semen metabolic profiles, the levels of detected metabolites were decreased in the latter ones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Buszewska-Forajta, Raczak-Gutknecht, Struck-Lewicka, Nizioł, Artymowicz, Markuszewski, Kordalewska, Matuszewski and Markuszewski.)

The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer.

Introduction : Image-guided surgery is becoming a new tool in colorectal surgery. Intraoperative visualisation of different structures using fluorophores helps during various steps of operations. In our report, we used two fluorophores-indocyanine green (ICG), and methylene blue (MB)-during different steps of colorectal surgery, using one camera system for two separate near-infrared wavelengths. Material and methods : Twelve patients who underwent complex open or laparoscopic colorectal surgeries were enrolled. Intravenous injections of MB and ICG at different time points were administered. Visualisation of intraoperative ureter position and fluorescent angiography for optimal anastomosis was performed. A retrospective analysis of patients treated in our departments during 2020 was performed, and data about ureter injury and anastomotic site complications were collected. Results : Intraoperative localisation of ureters with MB under fluorescent light was possible in 11 patients. The mean signal-to-background ratio was 1.58 ± 0.71. Fluorescent angiography before performing anastomosis using ICG was successful in all 12 patients, and none required a change in position of the planned colon resection for anastomosis. The median signal-to-background ratios was 1.25 (IQR: 1.22-1.89). Across both centres, iatrogenic injury of the ureter was found in 0.4% of cases, and complications associated with anastomosis was found in 5.5% of cases. Conclusions : Our study showed a substantial opportunity for using two different fluorophores in colorectal surgery, whereby the visualisation of one will not change the possible quantification analysis of the other. Using two separate dyes during one procedure may help in optimisation of the fluorescent properties of both dyes when using them for different applications. Visualisation of different structures by different fluorophores seems to be the future of image-guided surgery, and shows progress in optical technologies used in image-guided surgery.

Background: Uroplakins (UPs) are glycoproteins that play a specific role in the structure and function of the urothelium. Disorders which affect the normal expression of UPs are associated with the pathogenesis of infections and neoplasms of the urinary tract, primary vesicoureteral reflux, hydronephrosis and renal dysfunction. The appearance of uroplakins in the urine and/or plasma may be of potential importance in the detection of urinary tract dysfunction. The aim of the present study was to investigate uroplakin IIIa (UPIIIa) and uroplakin II (UPII) expression in patients with selected urological diseases., Methods: Plasma and urine from patients with benign prostatic hyperplasia (BPH), urethral stricture (US), urinary tract infection (UTI) and urolithiasis were compared to healthy people without urological disorders. UPs concentrations were measured by the immunoenzymatic method., Results: In patients with BPH and UTI, concentrations of UPIIIa in urine and plasma, as well as UPII in urine, were statistically significantly higher than in the control groups. In the US group, only the plasma UPIIIa concentration differed significantly from the control., Conclusion: The conducted research shows that benign urological diseases may affect the state of the urothelium, as manifested by increased concentrations of both UPs in patients' urine and plasma, especially in BPH and UTI.

Purpose: The purpose of this study was to assess the possibility of detecting sentinel lymph nodes (SLNs) and to perform analysis of lymphatic outflow in patients with suspicion of upper tract urothelial carcinoma (UTUC) with the use of a radioisotope-based technique., Methods: During 2018-2021, a prospective study was conducted on 19 patients with the suspicion of UTUC and for whom diagnostic ureterorenoscopy (URS) was planned. Technetium-99m ( 99m Tc) nanocolloid radioactive tracer injection and a tumor biopsy were performed for staging procedures. Three-dimensional (3D) reconstruction and fusion of images were performed for better localization of lymph nodes (LNs). Detection of SLNs and the analysis of the radiotracer outflow was conducted with the use of single-photon emission-computed tomography/computed tomography (SPECT/CT) lymphangiography., Results: The mean age of the patients was 73.4 years; 7 (36%) were male. Pathological staging from the biopsy was T0-8 (42%), Ta-7 (36%), T1-4 (21%). SLNs were detected in two of 19 cases (10%). In one patient a single SLN (5.3%) was visualized, and in another case (5.3%), multiple (double) radioactive lymph nodes were visualized. In 17 out of the 19 (89.5%) cases, no lymphatic outflow was observed, and out of these five cases (26.3%) of gravitational leakage of injected radiotracer to the retroperitoneal space was noted., Conclusions: We demonstrated that detection of SLNs in the upper urinary tract is possible yet challenging. Radiotracer injection in the upper urinary tract during ureterorenoscopy is difficult to perform, and the expected result of injection is unsatisfactory. Lymphatic outflow from the tumor site to the first LNs in our studied group of patients is visible in 10.5% of cases. SPECT/CT lymphangiography in cases of UTUC may provide valuable information about a patient's individual anatomy of the lymphatic system and the position of the first lymph nodes draining lymph with potential metastatic cells from the tumor.

Spin-orbit interactions which couple the spin of a particle with its momentum degrees of freedom lie at the center of spintronic applications. Of special interest in semiconductor physics are Rashba and Dresselhaus spin-orbit coupling. When equal in strength, the Rashba and Dresselhaus fields result in SU(2) spin rotation symmetry and emergence of the persistent spin helix only investigated for charge carriers in semiconductor quantum wells. Recently, a synthetic Rashba-Dresselhaus Hamiltonian was shown to describe cavity photons confined in a microcavity filled with optically anisotropic liquid crystal. In this Letter, we present a purely optical realization of two types of spin patterns corresponding to the persistent spin helix and the Stern-Gerlach experiment in such a cavity. We show how the symmetry of the Hamiltonian results in spatial oscillations of the spin orientation of photons traveling in the plane of the cavity.

Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients. In order to investigate the gene expression differences between tumors with low and high TSR, we applied multigene expression analysis (nCounter ® PanCancer Progression Panel, NanoString) of 42 tissue samples. TSR scores were categorized into low (<1 TSR) and high (≥1 TSR). In the pilot cohort, 31 patients (43.1%) were categorized as low and 41 (56.9%) as high TSR score, whereas 48 (23.0%) patients from the validation cohort were classified as low TSR and 161 (77.0%) as high. In both cohorts, high TSR appeared to indicate the shorter time to biochemical recurrence in PCa patients (Log-rank test, p = 0.04 and p = 0.01 for the pilot and validation cohort, respectively). Additionally, in the multivariate analysis of the validation cohort, TSR predicted BR independent of other factors, i.e., pT, pN, and age ( p = 0.04, HR 2.75, 95%CI 1.07-7.03). Our data revealed that tumors categorized into low and high TSR score show differential expression of various genes; the genes upregulated in tumors with low TSR score were mostly associated with extracellular matrix and cell adhesion regulation. Taken together, this study shows that high stroma content can play a protective role in PCa. Automatic EpCAM-based quantification of TSR might improve prognostication in personalized medicine for PCa.

This study aimed to define patients with renal cell cancer and coexisting tumor thrombus in order to address concerns regarding survival and prognostic factors after radical surgery. Several prognostic factors for overall survival (OS) were assessed in patients treated surgically at five institutions from 2012 to 2018. Univariate and multivariate analyses were used to determine the independent risk factors of OS. A total of 142 patients were eligible for further analysis (mean age of 64.75 years, 56% males). Most patients presented with clear cell carcinoma (95%). The Mayo stage was predominantly 0-1 (88%). Distant visceral metastases at the time of diagnosis were present in 36 patients (25%), whereas nodal metastases were present in 24 patients (16.9%). During the follow-up period (mean of 32.5 months), the 3-year OS rate reached 68.2%. The majority of patients received no adjuvant treatment ( n = 107). In a multivariable model predicting OS, regional lymph node status ( p < 0.001), distant metastases ( p = 0.009), tumor grade ( p = 0.002), duration of hospitalization ( p = 0.016), and Clavien-Dindo grade ( p = 0.047) were identified as independent prognostic factors. A subgroup of patients with specific clinicopathological factors may benefit most from the radical surgery, including patients without regional lymph node or distant metastases and with low tumor grades, whereas short hospitalization and low Clavien-Dindo grades represent additional independent prognostic factors.

Participation of anti-inflammatory interleukin-13 (IL-13) in the process of carcinogenesis was well studied. Angiogenesis plays a key role in the process of tumour growth and metastasis. Higher expression of angiogenin (ANG) have been proven in many types of cancers. The aim of the study was to more fully understand the significance of plasma IL-13 as an immunomodulator and ANG as a stimulator of the angiogenesis process in patients with bladder cancer (BC) and to investigate the relationship between parameters. These parameters were examined in the group of BC patients and in subgroups of BC depending on clinical stage: non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC), histopathologic malignancy low grade (LG), high grade (HG) and in primary and recurrent BC. The level of IL-13 and ANG in the plasma of BC patients and controls were measured by enzyme-linked immunosorbent assay. All calculations were done using the STATISTICA 13.3 (TIBCO software Inc.). Plasma levels of IL-13 and ANG were significantly higher in BC patients and in all patient subgroups examined than in the controls (p < 0.001). A negative significant correlation was found between ANG and IL-13 levels in BC-patients. Based on the receiver operating characteristic curves (ROC), IL-13 had good diagnostic value in BC. The presented results may suggest a relationship between angiogenesis and inflammation in the pathogenesis of bladder cancer and the development of this disease. With the increase of IL-13 level in BC-patients plasma, the ANG level decreased.

Reconstructing quantum states is an important task for various emerging quantum technologies. The process of reconstructing the density matrix of a quantum state is known as quantum state tomography. Conventionally, tomography of arbitrary quantum states is challenging as the paradigm of efficient protocols has remained in applying specific techniques for different types of quantum states. Here, we introduce a quantum state tomography platform based on the framework of reservoir computing. It forms a quantum neural network and operates as a comprehensive device for reconstructing an arbitrary quantum state (finite-dimensional or continuous variable). This is achieved with only measuring the average occupation numbers in a single physical setup, without the need of any knowledge of optimum measurement basis or correlation measurements.

Since varicocele is so common in infertile men, this study intends to analyse the relationships between varicocele and conventional semen characteristics, sperm nuclear DNA dispersion and oxidation-reduction potential (ORP) in semen. Varicocele-positive and varicocele-negative infertile men (study groups) showed significantly lower standard sperm parameters and higher sperm DNA fragmentation (SDF) and ORP in semen than healthy volunteers and subjects with proven fertility (control groups). A lower proportion of low SDF levels (0-15% SDF) and higher incidence of high SDF levels (>30% SDF), as well as a higher prevalence of high ORP values (>1.37 mV/10 6 sperm/mL), were found in the study groups vs. the control groups. Moreover, infertile men had significantly lower odds ratios (ORs) for low SDF levels and significantly higher ORs for high SDF levels and high ORP. SDF and ORP were negatively correlated with sperm number, morphology, motility and vitality. Furthermore, a significant positive correlation was found between SDF and ORP. The obtained results suggest that disorders of spermatogenesis may occur in varicocele-related infertility. These abnormalities are manifested not only by reduced standard semen parameters but also by decreased sperm DNA integrity and simultaneously increased oxidative stress in semen.