Search

Abstract The current study aimed to evaluate short‐ and long‐term complication rates and functional outcomes in a substantial cohort of patients undergoing ileal ureter interposition at two high‐volume medical centres. Materials and methods A retrospective single‐arm analysis was conducted on patients who underwent ureter reconstruction using ileum between 2003 and 2022 at the University Clinic of Cologne and the National Cancer Institute of Ukraine. Data on aetiology, surgical techniques, pre‐ and postoperative kidney function changes, readmission rates and complication management were collected. Postoperative complications were classified according to Clavien–Dindo, and estimated glomerular filtration rate (eGFR) was calculated using the CKD‐EPI formula. Results Results revealed 107 cases with consistent data. Within 90 days post‐surgery, 53% experienced complications, mainly graded as I–II. Grade III complications were seen in 13%, with two cases of grade IV complications leading to extended hospitalisation and patient death. The 90‐day mortality rate was 1.8%. Over a mean follow‐up of 52 months, clinically significant vesico‐renal refluxes occurred in 28%, with only 5.4% leading to persistent urinary tract infection. Antireflux techniques appeared to reduce urine upflow incidence compared with conventional interposition. Anastomosis stricture occurred in 15% of patients, with 63% requiring permanent re‐stenting and 37% needing re‐anastomosis. Metabolic acidosis was clinically significant in 7.5% of cases. A slight improvement in renal function was observed during the first year post‐surgery (average postoperative eGFR = 76 ± 22 ml/min; Mann–Witney U test, p = 0,0198). Affected kidney function improved in 56 (52%), was stable in 41 (38%) and deteriorated in 10 (9.3%). Loss of kidney function on the surgery side was seen in 4 (3.7%) patients and resulted in nephrectomy in 3 (2.8%) cases. Conclusion Ileal ureter interposition demonstrated a favourable safety profile and functional outcomes. This surgical intervention provides an effective tension‐free bypass, irrespective of healthy ureter length.

The aim of this work was to gain an initial impression of the surface quality that can be achieved with additively manufactured ceramic components. For this purpose, an assessment body was generated, which has partially double-curved surfaces that can be scanned using a confocal microscope. After manufacturing using Vat Photopolymerization for ceramic components (CerAM VPP) with a commercial alumina suspension (Lithalox 350, Lithoz, Vienna, AUT) and thermal processing, the respective surface was measured at four different geometric areas. For evaluation, line sections were extracted to calculate Ra values as well as to determine Sa values for surfaces. Ra and Sa values were determined in all areas, reaching always values below 2.5 μm. The surface quality is therefore an order of magnitude lower than that of typical metallic AM components.

Abstract After decades where human spaceflight missions have been reserved to low Earth orbit, recent years have seen mission proposals and even implemented plans, e.g. with the mission Artemis I, for returning to the lunar surface. SpaceX has published over various media (e.g., its official website, conference presentations, user manual) conceptual information for its reusable Starship to enable human exploration missions to the Martian surface by the end of the decade. The technological and human challenges associated with these plans are daunting. Such a mission at that distance would require excellent system reliability and in-situ-resource utilization on a grand scale, e.g. to produce propellant. The plans contain little details however and have not yet been reviewed concerning their feasibility. In this paper we show significant technological gaps in these plans. Based on estimates and extrapolated data, a mass model as needed to fulfill SpaceX’s plans could not be reproduced and the subsequent trajectory optimization showed that the current plans do not yield a return flight opportunity, due to a too large system mass. Furthermore, significant gaps exist in relevant technologies, e.g. power supply for the Martian surface. It is unlikely that these gaps can be closed until the end of the decade. We recommend several remedies, e.g. stronger international participation to distribute technology development and thus improve feasibility. Overall, with the limited information published by SpaceX about its system and mission scenario and extrapolation from us to fill information gaps, we were not able to find a feasible Mars mission scenario using Starship, even when assuming optimal conditions such as 100% recovery rate of crew consumables during flight.

The assessment of artificial intelligence (AI) application for prediction of internal combustion engine (ICE) performance and its impact on CO2 emissions is conducted in this paper. Three machine learning techniques (Random Forest, Support Vector Regression, and Semi-supervised Deep Fuzzy C-means) are developed to analyze inputs from an engine simulation software package database. By employing these sophisticated mathematical techniques, we successfully assess the influence of engine power range on CO2 emissions in this paper. Moreover, the framework facilitates segment-based analysis, which enables segment-specific assessment of CO2 emission based on metrics such as average traveled distance and average daily trips in urban and rural settings. The Deep Fuzzy C-means model (DFCM) seems promising to predict engine performance, with high predictive accuracy and a coefficient of determination (R2) approaching unity. The results indicate that integration of inter-class and intra-class distinctions, along with considering the interquartile range of engine power provides invaluable insights for the formulation of strategies aimed at overhauling the passenger vehicle fleet and advancing decarbonization efforts. By implementing the proposed innovative techniques, we aspire to enrich the precision of ICE emission models, leading to more reliable calculations and an enhanced understanding of the environmental implications associated with vehicles.

Accurately measuring vehicle mileage is pivotal in precise CO2 emission calculations and the development of reliable emission models. Nonetheless, mileage data gathered from surveys relying on self-estimation, garage reports, and other estimation-based sources often yield rough approximations that substantially deviate from the actual mileage. To tackle this issue, we present a comprehensive framework aimed at bolstering the accuracy of CO2 emission models. This paper harnesses two innovative techniques: the deep learning semi-supervised fuzzy C-means (SSFCM) and polynomial classifier models. By leveraging these sophisticated mathematical techniques, we achieve successful classification of passenger vehicles, enabling more precise evaluations of average mileage. Real data shows that vehicles in Switzerland considerably exceed the estimated mileage in the years following the first registration of the vehicle. The difference lies in the covered mileage after vehicles reach five years of age. Our framework supports segment-based analysis for assessing average mileage and enhancing emission models for better understanding of vehicle-related environmental impact.

Current political and sociological efforts to respond to the need for more environmentally friendly technologies have inspired a revival of wood and wood-based material utilization in space systems. The popularity of these materials has faded since their widespread use in the early days of aerospace engineering. This work reviews the literature to provide an overview of use cases, the motivation for using wood and wood-based materials and the challenges involved. A small number of applications were identified in which wood and wood-based materials were preferred over non-renewable raw materials. They are mainly applied for less-stressed disposable components or as a thermal protection material. It can be shown that the applied wooden materials have advantages such as low production costs, easy availability, easy and environment-friendly decomposition and low weight. However, only a limited number of applications have achieved a high level of technological readiness so far. Properties such as anisotropy and a lack of uniformity, defects in wood, the quantity available material and a lack of standards for the certification of wooden materials represent challenges. These are addressed in the current research, which additionally focuses on sustainable growth, enhanced environmental friendliness and advanced lightweight design.

A cold-gas test campaign has been conducted at the DLR’s P6.2 test bench in Lampoldshausen, with the objective of investigating the linear aerospike nozzle flow in interaction with secondary injection thrust vector control (SITVC). In this campaign, the influence of nozzle truncation, injection position and injection pressure on the nozzle surface and base pressure is analysed using pressure probes and Schlieren flow-visualisation techniques. The effects of injection position and truncation on the nozzle surface pressure development are comparable for all geometric variations, resulting in a locally increased static pressure upstream and a locally decreased static pressure downstream of the injection. The magnitude and dimension of these high- and low-pressure regions are correlated with the injection pressure. However, the influence of injection position and truncation on the base pressure is not entirely predictable by the named parameters, indicating an interdependence between both geometric parameters. Finally, the required pressure ratio of injection to the primary flow to ensure sonic injection has been analysed on TUD’s cold-gas test bench. This allows the respective injection position-dependent threshold to be identified. The analysis reveals that these experiments have been conducted under transsonic injection conditions.

Background: Detection of circulating tumor-derived material (cTM) in the peripheral blood (PB) of cancer patients has been shown to be useful in early diagnosis, prediction of prognosis, and disease monitoring. However, it has not yet been thoroughly evaluated for pediatric sarcoma patients. Methods: We searched the PubMed and EMBASE databases for studies reporting the detection of circulating tumor cells, circulating tumor DNA, and circulating RNA in PB of pediatric sarcoma patients. Data on performance in identifying cTM and its applicability in diagnosis, and evaluation of tumor characteristics, prognostic factors, and treatment response was extracted from publications. Results: A total of 79 studies were assigned for the present systematic review, including detection of circulating tumor cells (116 patients), circulating tumor DNA (716 patients), and circulating RNA (2887 patients). Circulating tumor cells were detected in 76% of patients. Circulating DNA was detected in 63% by targeted NGS, 66% by shallow WGS, and 79% by digital droplet PCR. Circulating RNA was detected in 37% of patients. Conclusion: Of the cTM from Ewing's sarcoma and rhabdomyosarcoma ctDNA proved to be the best target for clinical application including diagnosis, tumor characterization, prognosis, and monitoring of disease progression and treatment response. For osteosarcoma the most promising targets are copy number alterations or patient specific micro RNAs, however, further investigations are needed to obtain consensus on clinical utility.

Immunoglobulin A (IgA) is the most abundant antibody isotype in humans and anti-HLA IgA was found in sera of transplant recipients. Focusing on patients awaiting kidney re-transplantation, we tested the impact of anti-HLA-class I/II IgA antibodies on graft survival. We analyzed 276 patients with and 238 without allograft failure. Eight motives of the Fcα receptor (FCAR) and Fcγ receptor were analyzed in patients with allograft failure. The distribution of anti-HLA IgA1/A2 and IgG antibodies differed significantly (p < 0.0001) between both patient groups, and IgA1 plus IgA2 antibodies were more abundant in patients with allograft failure. Allograft survival was significantly impaired if anti-HLA-class I plus II IgA was present, in the first 105 months (9 years) of follow-up (median of 43 vs. >105 months, p = 0.007). Patients with anti-HLA IgA and IgG vs. anti-HLA IgG only had a significantly shorter allograft survival within that follow-up period (88 vs. >105 months, p = 0.008). Moreover, allograft survival was shorter (p = 0.02) in carriers of GG vs. AA + AG genotypes of FCAR rs16986050. Thus, the presence of anti-HLA IgA plus IgG vs. IgG only was associated with shorter kidney allograft survival and FCAR motives may impact on graft survival.

Objectives: To evaluate an overview of the past, present, and future of robotic surgery. To provide insight and focus on the current status of the field of robotic systems for urological surgery with outcomes and discuss future perspectives in terms of other operative techniques and new robotic platforms. Evidence acquisition: The authors undertook a non-systematic literature review using PubMed, Medline, and Google search. They used the search terms “robotic uro-surgery”, “laparoscopic”, “minimally invasive surgery”, “future of robotics”, “global robotic market growth”, “geographical distribution”, and “cost-effectiveness”. Evidence synthesis: Robotic surgery has embraced and extended almost all aspects of uro-surgical fields since its introduction three decades ago. There are definite advantages of robots to the surgeons and patients. It has become new standard of care for many surgical procedures. Innovation and technological advances are continuing and new with more precise robots are emerging. The major downside is cost. Despite the high cost, robot market is growing. Conclusion: Over the past decade, minimally invasive approaches have virtually revolutionised surgery and robotic surgery has accelerated these changes. Without doubt, robotic urologic surgery is here to stay and will expand further in all surgical disciplines. Utilisation of robotics should be coupled with a reduction in costs to healthcare systems, and improved clinical outcomes for the general population rather than a privileged few. Therefore, making this expensive technology more affordable must be part of the equation.

Abstract Background The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms. Methods The effect of COVID-19 on lower urinary tract function was studied in a prospective multi-centre, observational study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran. Results None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19% of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48 to 61% in the Tabriz cohort (p-value = 0.03) and from 30 to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 30 to 58%. (p-value =0.039). Conclusion Patients admitted with COVID-19 did not report to have any lower urinary tract symptoms, even those patient who had a positive Urine SARS-CoV-2 PCR. In addition, hematuria, WBC in urine as well as SARS- CoV-2 presence in urine, were found to be strong negative prognostic factors in admitted COVID-19 patients.

Abstract The question of whether a singularity can form in an initially regular flow, described by the 3D incompressible Navier–Stokes (NS) equations, is a fundamental problem in mathematical physics. The NS regularity problem is super-critical, i.e., there is a ‘scaling gap’ between what can be established by mathematical analysis and what is needed to rule out a singularity. A recently introduced mathematical framework—based on a suitably defined ‘scale of sparseness’ of the regions of intense vorticity—brought the first scaling reduction of the NS super-criticality since the 1960s. Here, we put this framework to the first numerical test using a spatially highly resolved computational simulation performed near a ‘burst’ of the vorticity magnitude. The results confirm that the scale is well suited to detect the onset of dissipation and provide numerical evidence that ongoing mathematical efforts may succeed in closing the scaling gap.

Checkpoint blocking therapies are used to treat metastatic melanoma, but can have adverse immune-mediated effects, including liver pathology. Here the authors identify an expanded pool of CD4+ effector memory T cells resulting from prior CMV exposure as a risk factor for this adverse effect in these patients.

This paper aims to introduce a scientific Semi-Supervised Fuzzy C-Mean (SSFCM) clustering approach for passenger cars classification based on the feature learning technique. The proposed method is able to classify passenger vehicles in the micro, small, middle, upper middle, large and luxury classes. The performance of the algorithm is analyzed and compared with an unsupervised fuzzy C-means (FCM) clustering algorithm and Swiss expert classification dataset. Experiment results demonstrate that the classification of SSFCM algorithm has better correlation with expert classification than traditional unsupervised algorithm. These results exhibit that SSFCM can reduce the sensitivity of FCM to the initial cluster centroids with the help of labeled instances. Furthermore, SSFCM results in improved classification performance by using the resampling technique to deal with the multi-class imbalanced problem and eliminate the irrelevant and redundant features.

The overall level of emissions from the Swiss passenger cars is strongly dependent on the fleet composition. Despite technology improvements, the Swiss passenger cars fleet remains emissions intensive. To analyze the root of this problem and evaluate potential solutions, this paper applies deep learning techniques to evaluate the inter-class (namely micro, small, middle, upper middle, large and luxury class) and intra-class (namely sport utility vehicle and non-sport utility vehicle) differences in carbon dioxide (CO2) emissions. This paper takes full use of novel semi-supervised fuzzy C-means (SSFCM), random forest and AdaBoost models as well as model fusion to successfully classify passenger vehicles and enable segment-based CO2 emission evaluations.

IntroductionSince the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines.Materials and methodsTo longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses.ResultsA total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate.ConclusionWhile the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

Abstract Background SelectMDx is a urinary biomarker test for determining prostate cancer risk. Aim In a group of patients with a biopsy proven prostate cancer (PCa) who had undergone a multi parametric Magnetic Resonance Imaging (mpMRI) and urinary biomarker test with SelectMDx, we studied the additive value of SelectMDx to mpMRI and correlated that to the radical prostatectomy histology. Methods and results Thirty‐nine consecutive patients with a positive prostate biopsy were included in the study. They all had mpMRI and SelectMDx and underwent a radical prostatectomy. Overall, the mpMRI showed a PIRADS ≤3 lesion in seven cases out of the 39 patients. Significant lesions (PIRADS ≥4) were found in 32 cases (82%), that is, in 17 cases a PIRADS 5 lesion and in 15 cases a PIRADS 4 lesion. The mpMRI missed significant PCa in seven cases (18%) who had a PIRADS ≤3 lesion but had a significant PCa on final histology after RP. In our study, the positive predictive values of mpMRI were 97% and that of the SelectMDx was 100%. Conclusion In this real‐life selected group of consecutive patients with a confirmed positive PCa biopsy and available mpMRI, the liquid biopsy test with SelectMDx, did not provide an additional information about the PCa clinical significance. The addition of SelectMDx was only found valuable in those patients who had a very high‐risk PCa (ie, GS ≥8) who had a positive SelectMDx test outcome despite of a negative mpMRI outcome.

Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients.Methods: We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined.Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA.Conclusion: Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients.

High performance ceramics, particularly Ceramic Matrix Composite (CMC) materials found their way into liquid rocket engines. Yet, so far, mainly carbide or nonoxide CMCs have been of interest. This paper explores the potential and challenges of oxide–oxide ceramic matrix composites (OCMCs) for application in rocket thrust chambers. Therefore, strength, leakage and hot gas tests are conducted with material samples. A particular focus lies on the application of coatings to seal the permeability inherent to the material. Furthermore, prototypes in the form of flame tubes, ceramic chambers with nozzles and ceramic chambers with graphite inlays are developed and investigated experimentally in test firings. The results show that a recrystallised glass of a Y-Al-Si-O compound can successfully create an impermeable coating of the OCMC without affecting its damag-tolerant behaviour. However, the prototype developments show that it is still very challenging to manufacture even slightly complex structures without critical failures. Nevertheless, OCMC structures of relatively simple geometries showed promising results in hot firings and could be used as a lightweight housing, while the inner contour of the chamber and nozzle are realised, e.g., by a graphite inlay of appropriate quality.

Synthetic fuels produced with renewable surplus electricity depict an interesting solution for the decarbonization of mobility and transportation applications which are not suited for electrification. With the objective to compare various synthetic fuels, an analysis of all the energy conversion steps is conducted from the electricity source, i.e., wind-, solar-, or hydro-power, to the final application, i.e., a vehicle driving a certain number of miles. The investigated fuels are hydrogen, methane, methanol, dimethyl ether and Diesel. While their production process is analyzed based on literature, the usage of these fuels is analyzed based on chassis dynanometer measurement data of various EURO-6b passenger vehicles.Conventional and hybrid power-trains as well as various carbon dioxide sources are investigated in two scenarios. The first reference scenario considers market-ready technology only, while the second future scenario considers technology which is currently being developed in industry and assumed to be market-ready in near future. With the results derived in this study and with consideration of boundary conditions, i.e., availability of infrastructure, storage technology of gaseous fuels, energy density requirements, etc., the most energy efficient of the corresponding suitable synthetic fuels can be chosen. Keywords: Power-to-gas, Power-to-liquid, Synthetic fuels, Renewable fuels, Well-to-wheels, Well-to-miles

Background: Scientific congresses are an important medium for presenting recent clinical findings. Publication of abstracts allows wider dissemination.Objectives: To determine the publication rates of prostate cancer abstracts presented at the annual congress of the European Association of Urology (EAU).Design, Setting, and Participants: All abstracts with the term prostate cancer or carcinoma presented at the congress of the European Association of Urology from 2015 to 2018 were analyzed. We captured their publication rate, journal impact factor and time to publication. Moreover, we formulated a scoring system to determine the grade of discrepancy between the conclusions mentioned in the congress abstract and published abstract.Results: A total of 834 abstracts presented at EAU annual meeting included prostate cancer or carcinoma in their title. We recorded a publication rate of 56.8% with 474 of the 834 abstracts being published with a mean time of 12.5 months.Conclusion: Approximately, 57% of the prostate cancer abstracts presented at the EAU congress are published in peer reviewed journals. This acceptance rate indicates the high distribution and dissemination of these abstracts.

IntroductionAfter the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries.Material and methodsAn email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses.Results27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers-however, the number of COVID-19 patients and urologists did not reach double digits.ConclusionThe German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.

Pyeloplasty is one of the most common urological reconstructive interventions. Since the presentation of the first open pyeloplasty by Anderson and Hynes in 1949, the management of ureteropelvic junction obstruction has dramatically developed. The most immense progress was made in the 1990s with the introduction of laparoscopy. A multitude of new minimal surgical techniques have been introduced since then. In the last few years, the innovations were based on refinement of already-existing techniques and technology. With this aim, single-port surgery, three-dimensional vision for laparoscopy, robotic technology, and alternative techniques for creating the anastomosis-like fibrin glue have been introduced. This unsystematic review is timely, and the scientific interest is to present and discuss some of the latest advances in surgical techniques and different approaches for the intra- and post-operative management in pyeloplasty. To the best of our knowledge, this is the only review looking at the recent advances in urological surgical techniques for pyeloplasty during the last few years with a focus on new technology and surgical techniques.

Robust anti-tumor immunity requires innate as well as adaptive immune responses. We have shown that plasmacytoid dendritic cells develop killer cell-like activity in melanoma cell cocultures after exposure to the infectious but replication-deficient herpes simplex virus 1 (HSV-1) d106S. To combine this innate effect with an enhanced adaptive immune response, the gene encoding human MelanA/MART-1 was inserted into HSV-1 d106S via homologous recombination to increase direct expression of this tumor antigen. Infection of Vero cells using this recombinant virus confirmed MelanA expression by Western blotting, flow cytometry, and immunofluorescence. HSV-1 d106S-MelanA induced expression of the transgene in fibroblast and melanoma cell lines not naturally expressing MelanA. Infection of a melanoma cell line with CRISPR-Cas9-mediated knockout of MelanA confirmed de novo expression of the transgene in the viral context. Dependent on MelanA expression, infected fibroblast and melanoma cell lines induced degranulation of HLA-matched MelanA-specific CD8+ T cells, followed by killing of infected cells. To study infection of immune cells, we exposed peripheral blood mononuclear cells and in vitro-differentiated macrophages to the parental HSV-1 d106S, resulting in expression of the transgene GFP in CD11c+ cells and macrophages. These data provide evidence that the application of MelanA-encoding HSV-1 d106S could enhance adaptive immune responses and re-direct MelanA-specific CD8+ T cells to tumor lesions, which have escaped adaptive immune responses via downregulation of their tumor antigen. Hence, HSV-1 d106S-MelanA harbors the potential to induce innate immune responses in conjunction with adaptive anti-tumor responses by CD8+ T cells, which should be evaluated in further studies.

The ongoing threat of viral infections and the emergence of antiviral drug resistance warrants a ceaseless search for new antiviral compounds. Broadly-inhibiting compounds that act on elements shared by many viruses are promising antiviral candidates. Here, we identify a peptide derived from the cowpox virus protein CPXV012 as a broad-spectrum antiviral peptide. We found that CPXV012 peptide hampers infection by a multitude of clinically and economically important enveloped viruses, including poxviruses, herpes simplex virus-1, hepatitis B virus, HIV-1, and Rift Valley fever virus. Infections with non-enveloped viruses such as Coxsackie B3 virus and adenovirus are not affected. The results furthermore suggest that viral particles are neutralized by direct interactions with CPXV012 peptide and that this cationic peptide may specifically bind to and disrupt membranes composed of the anionic phospholipid phosphatidylserine, an important component of many viral membranes. The combined results strongly suggest that CPXV012 peptide inhibits virus infections by direct interactions with phosphatidylserine in the viral envelope. These results reiterate the potential of cationic peptides as broadly-acting virus inhibitors.

Objective To validate and evaluate the applicability of a new score to describe postsurgical analgesic consumption in urological and surgical patients across different categories of pain medications and the invasiveness of medical interventions. Materials and Methods The cumulative analgesic consumption score (CACS) was determined for two cohorts of patients split into three groups with surgeries involving clinically distinct levels of invasiveness (n = 2 x 60). Nonparametric statistical analyses were performed to determine differences between the CACS among the different groups and to assess the correlation between CACS and numeric rating scale (NRS) values for pain intensity. Results The score was determined for postoperative days 1 and 2 and revealed median scores of 0 (0-11), 3 (0-22) and 10 (6-17) for UA (urological patients from group A), UB (group B) and UC (group C), respectively, and 4 (0-20), 8 (0-38) and 17 (7-68) for SA (surgical patients from group A, SB (group B) and SC (group C), respectively. CACS enabled reliable differentiation between groups involving different levels of invasiveness (p < 0.001). CACS and peak NRS values showed variable degrees of correlation, as expressed by levels of significance ranging from p < 0.001 to p = 0.34 (NS). Conclusions The CACS is a valid and easily applicable tool to describe postsurgical analgesic consumption in urological and surgical patients. It can be used as a surrogate parameter to assess postsurgical pain and the invasiveness of surgical procedures. These aspects may be measured to compare surgical procedures, in both clinical trials and clinical practice settings.

No Abstract

Fusion proteins composed of the histone methyltransferase mixed-lineage leukemia (MLL) and a variety of unrelated fusion partners are highly leukemogenic. Despite their prevalence, particularly in pediatric acute leukemia, many molecular details of their transforming mechanism are unknown. Here, we provide mechanistic insight into the function of MLL fusions, demonstrating that they capture a transcriptional elongation complex that has been previously found associated with the eleven-nineteen leukemia protein (ENL). We show that this complex consists of a tight core stabilized by recursive protein-protein interactions. This central part integrates histone H3 lysine 79 methylation, RNA Polymerase II (RNA Pol II) phosphorylation, and MLL fusion partners to stimulate transcriptional elongation as evidenced by RNA tethering assays. Coimmunoprecipitations indicated that MLL fusions are incorporated into this complex, causing a constitutive recruitment of elongation activity to MLL target loci. Chromatin immunoprecipitations (ChIP) of the homeobox gene A cluster confirmed a close relationship between binding of MLL fusions and transcript levels. A time-resolved ChIP utilizing a conditional MLL fusion singled out H3K79 methylation as the primary parameter correlated with target expression. The presence of MLL fusion proteins also kept RNA Pol II in an actively elongating state and prevented accumulation of inhibitory histone methylation on target chromatin. Hox loci remained open and productive in the presence of MLL fusion activity even under conditions of forced differentiation. Finally, MLL-transformed cells were particularly sensitive to pharmacological inhibition of RNA Pol II phosphorylation, pointing to a potential treatment for MLL. In summary, we show aberrant transcriptional elongation as a novel mechanism for oncogenic transformation.

For solving complex analytical tasks networking has proven to be extremely useful. Networking in Analytical Chemistry shows various aspects. The use of a pool of different, complementary instrumental methods for ambitious analytical investigations is fundamental. Furthermore, stimulating a transdisciplinary approach through dynamic team formation within a transparent, flexible organization is an essential management task. Two case studies illustrating the networking approach at EMPA in complex analytical service and R & D projects are presented. The result is a comprehensive approach in analytical chemistry, activating synergy.

Based on our current knowledge, particulate matter in Diesel-engine exhaust gases should be classified as toxic. The current regulations define limits only for the total mass emission of particulate matter given in g/km or per energy unit. Other properties such as particle size or chemical composition are not yet considered.The EMPA has been concerned with the detailed analysis of particulate emission since 1992. For this investigation, samples of Diesel exhaust gases and heating-system flue gases are being used. The Diesel engine is operating under various conditions whereas two different oil-burner types are being used in the heating system. The burners are designated 'yellow-flame' and 'blue-flame'.The size distribution of the particles, their morphology, and chemical composition are determined. The initial results show that the particle properties depend on the combustion processes and operating conditions. This investigation is being continued.