关键词： liquid biopsy   circulating tumor DNA   high-throughput nucleotide sequencing   urinary bladder neoplasms   urine  

摘要： Purpose: Next-generation sequencing (NGS)-based profiling of both urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) shows promise for noninvasive detection and surveillance of urothelial bladder cancer (UBC). However, the analytical performance of these assays remains undefined in the real-world setting. Here, we sought to evaluate the concordance between tumor DNA (tDNA) profiling and utDNA or ctDNA assays using a UBC patient cohort from the intended-use population. Materials and Methods: Fifty-nine cases with pathologically confirmed disease and matching tissue/urine pairs were prospectively enrolled. Baseline peripheral blood mononuclear cell and plasma specimens were collected during clinic visits. The Predicine CARE (TM) NGS assay was applied for ultra-deep targeted sequencing and somatic alteration identification in tDNA, utDNA and ctDNA. Results: Diverse quantitative metrics including cancer cell fraction, variant allele frequency and tumor mutation burden were invariably concordant between tDNA and utDNA, but not ctDNA. The mutational landscapes captured by tDNA or utDNA were highly similar, whereas a considerable proportion of ctDNA aberrations stemmed from clonal hematopoiesis. Using tDNA-informed somatic events as reference, utDNA assays achieved a specificity of 99.3%, a sensitivity of 86.7%, a positive predictive value of 67.2%, a negative predictive value of 99.8% and a diagnostic accuracy of 99.1%. Higher preoperative utDNA or tDNA abundance correlated with worse relapse-free survival. Actionable variants including FGFR3 alteration and ERBB2 amplification were identified in utDNA. Conclusions: Urine-based molecular pathology provides a valid and complete genetic profile of bladder cancer, and represents a faithful surrogate for genotyping and monitoring newly diagnosed UBC.

关键词： Cardiac arrest   Cardiopulmonary resuscitation   Pulse rate   Pulse oximetry plethysmographic waveform   Feedback device  

摘要： Feedback indicators can improve chest compression quality during cardiopulmonary resuscitation (CPR). However, the application of feedback indicators in the clinic practice is rare. Pulse oximetry has been widely used and reported to correlate spontaneous circulation restoration during CPR. However, it is unclear if pulse oximetry can monitor the quality of chest compression. We hypothesized that pulse rate monitored by pulse oximetry can be used as a feedback indicator of the chest compression rate during CPR in a porcine model of cardiac arrest. Seven domestic male pigs (30-35 kg) were utilized in this study. Eighteen intermittent chest compression periods of 2 min were performed on each animal. Chest compression and pulse oximetry plethysmographic waveforms were recorded simultaneously. Chest compression and pulse rates were calculated based on both waveforms. Compression interruption and synchronous pulse interruption times were also measured. Agreement was analyzed between pulse rates and synchronous chest compression rates, as well as between compression interruption times and synchronous pulse interruption times. A total of 126 compression periods of 2 min were performed on seven animals. Interclass correlation coefficients and Bland-Altman analysis revealed reliable agreement between pulse rates and synchronous chest compression rates. Similarly, compression interruption and synchronous pulse interruption times obtained also showed high agreement. Pulse rate can be used as an alternative indicator of chest compression rate during CPR in a porcine model of cardiac arrest. Pulse interruption time also can be used to reflect compression interruption time precisely in this model.

关键词： varicocele   ultrasound   semen analysis  

摘要： Purpose: We assessed the role of standing vs supine scrotal ultrasound (SUS) for varicocele assessment by evaluating differences in clinical outcomes. Materials and Methods: We retrospectively reviewed men from 2008-2020 diagnosed with varicocele who had documented SUS with both supine and standing assessments with and without Valsalva. Clinical outcomes (semen parameters, TUNEL and serum testosterone [T]) after microsurgical varicocelectomy were compared among men who had varicoceles diagnosed by standing SUS (vein size >2.5 mm, vein size >3.0 mm or reversal of flow) to those who would have been missed on supine SUS only. Results: A total of 349 men underwent varicocelectomy (right: 5 [1.4%];left: 118 [33.8%];bilateral: 226 [64.8%]). Disagreement between those with abnormal standing vs normal supine for vein size >2.5 mm was: 56 men (16.1%) on the right and 31 men (8.9%) on the left, for vein size >3.0 mm was: 64 men (18.3%) on the right, and 56 men (16.1%) on the left, and for flow reversal was: 36 (14.0%) on the right and 40 (15.4%) on the left. For those >2.5 mm, only T had significant improvements on the left (p=0.05). For those >3.0 mm significant differences were seen for sperm motility on the right (p=0.04), and TUNEL (p=0.04) and T (p <0.01) on the left. For flow reversal, significant differences were seen for serm concentration (p<0.01), morphology (p[0.03) and volume (p=0.05) on the right and TUNEL on the left (p=0.02). Conclusions: Standing SUS identifies a greater number of men who would have been missed using supine SUS only.

关键词： admixtures   prestressed concrete   sustainability  

摘要： The precast industry, due to its specific early-age strength requirements for hollowcore (HC) slab products, has been reluctant to introduce alternative cementitious materials such as ground granulated blast-furnace slag (GGBS) due to the slower strength development of such materials. This paper reports on a study undertaken at a precast production facility to examine how to overcome the consequences of strength loss due to the replacement of up to 50% of CEM I (42.5R), as usually used in cold weather conditions, with GGBS, for environmental or durability reasons. The GGBS concrete slabs were activated using thermal, chemical and mechanical means to enhance their early-age strength gain. The results were compared at early ages in terms of the temperature profile during curing, cube compressive strengths, load-carrying capacities for transportability requirements, ultimate load and short-term creep. In addition, 28 d densities and strengths were compared for in situ cubes and cores extracted from HC slab samples. The experimental results showed a favourable potential for replacing CEM I (42.5R) cement with up to 50% GGBS in winter without compromising on factory productivity.

摘要： The nucleobase derivative 5-aminouracil (AUr, C4H5N3O2) is of interest for its biological activity, yet the solid state structure of this compound has remained elusive owing to its propensity to crystallize as aggregates of microcrystalline particles. Here we report the first single-crystal structure of AUr determined from synchrotron x-ray diffraction data. An early crystal structure prediction effort, which assumed that AUr was rigid in the isolated molecule optimized conformation, provided several poor matches to the simulated PXRD pattern. Revisiting these crystal structures, by periodic electronic level modelling (PBE-TS optimization) gave more realistic relative lattice energies, but a good match to the experimental powder pattern required using the experimental cell parameters. PXRD and Raman spectroscopy suggest that phase impurities may be present in the bulk crystallization product, though the identity of alternative polymorphs could not be confirmed on the basis of the data available.

关键词： 3' mRNA-Seq   alternative polyadenylation   Large White pigs   porcine reproductive and respiratory syndrome virus   Tongcheng pigs  

摘要： Alternative polyadenylation (APA) is a widespread post-transcriptional regulation mechanism that increases the biological complexity of transcriptome and proteome. However, it is unclear whether APA regulation plays a role in genetic resistance to porcine reproductive and respiratory syndrome virus (PRRSV). Here, we reported genome-wide APA regulation of porcine alveolar macrophages in PRRSV-resistant Tongcheng (TC) pigs and PRRSV-susceptible Large White (LW) pigs upon PRRSV infection. Using 3' mRNA sequencing strategy, we detected 75 981 high-quality APA sites in porcine alveolar macrophages of TC and LW pigs. Furthermore, 1202 and 1089 differentially expressed APA sites, as well as 79 and 117 untranslated region-APA switching genes were identified in TC pigs and LW pigs upon PRRSV infection respectively. The APA events in TC pigs and LW pigs were involved in different biological pathways, while APA events in TC pigs are directly associated with the immune response to PRRSV infection. In addition, we identified genetic variations affecting polyadenylation signal between TC pigs and LW pigs. These findings would provide helpful information on APA regulation for further understanding of genetic resistance to PRRSV.

关键词： Household fermentable waste   cement industry   alternative fuel   life cycle assessment   life cycle costing  

摘要： The scope of this paper is to examine the environmental and economic performance of an alternative household fermentable waste (HFW) management paradigm, developed within the framework of the HORIZON 2020 project Waste4think. In Greece, the business-as-usual scheme for the management of HFW is its disposal in landfills as part of mixed waste. Waste4think developed an alternative approach based on the benefits of source separation. Specifically, source separated HFW is taken to a drying/shredding plant, located in the municipality, for the production of a high-quality biomass product called FORBI. Alternative approaches have been examined for the exploitation of FORBI. In this work, the use of FORBI as an alternative fuel for the cement industry is assessed using life cycle assessment (LCA) and life cycle costing (LCC) tools. The results show that the proposed HFW management framework performs better than the baseline scenario both in economic and environmental terms. However, focus should be given to the optimisation of the drying/shredding process in order to reduce its energy intensity and environmental loadings.

关键词： ADHD   behavior therapy   meta-regression   pharmacotherapy   treatment efficacy  

摘要： Background There have been various therapies for attention-deficit/hyperactivity disorder (ADHD), but the previous meta-analysis of ADHD efficacy remains unclear. This study aims to systemically meta-regress the effect sizes (ES) of psychostimulant pharmacotherapy (methylphenidate and lisdexamfetamine), non-stimulant pharmacotherapy (atomoxetine and alpha-2 agonists), psychosocial therapy (parental behavioral therapy [PBT]), combination therapy (psychostimulant plus PBT), and alternative/complementary interventions to determine the right treatment for ADHD. Methods We searched various ADHD interventions from the MEDLINE and PubMed databases (National Center for Biotechnology Information) between January 1, 1980, and July 30, 2018. Following the meta-analysis of random effects, the meta-regression analyses were used to explore factors potentially influencing treatment efficacy. The confounding variables included type of treatment, type of study, age, type of symptom scale used, and year of publication. Results A total of 107 trials (n=9883 participants) were included. After adjustment, compared with the psychostimulant therapy (28 trial, 2134 participants), non-stimulant pharmacotherapy (28 trials, 4991 participants) and alternative/complement intervention (25 trials, 1195 participants) were less effective by the ES of -0.384 (P=.004) and -0.419 (P=.028), respectively. However, compared with psychostimulant, PBT (19 trials, 1122 participants;ES=-0.308, P=.095) and the combination of psychostimulant and PBT (7 trials, 441participants;ES=-0.196, P=.209) did not differ significantly. Conclusions Psychostimulant therapy surpassed non-stimulant pharmacotherapy and alternative/complement intervention. Psychostimulant therapy, PBT, and the combination of psychostimulant therapy and PBT appear to be similar in efficacy according to this meta-regression.

关键词： Myeloma   Risk factors   Medicine/Public Health   general   Internal Medicine   Intensive / Critical Care Medicine   Cancer Research   Oncology   Hematology  

摘要： Clinical and genetic risk factors are currently used in multiple myeloma (MM) to stratify patients and to design specific therapies. However, these systems do not capture the heterogeneity of the disease supporting the development of new prognostic factors. In this study, we identified active promoters and alternative active promoters in 6 different B cell subpopulations, including bone-marrow plasma cells, and 32 MM patient samples, using RNA-seq data. We find that expression initiated at both regular and alternative promoters was specific of each B cell subpopulation or MM plasma cells, showing a remarkable level of consistency with chromatin-based promoter definition. Interestingly, using 595 MM patient samples from the CoMMpass dataset, we observed that the expression derived from some alternative promoters was associated with lower progression-free and overall survival in MM patients independently of genetic alterations. Altogether, our results define cancer-specific alternative active promoters as new transcriptomic features that can provide a new avenue for prognostic stratification possibilities in patients with MM.

关键词： proteomics   prostatic neoplasms   biomarkers   gonadotropin-releasing hormone   cardiovascular physiological phenomena  

摘要： Purpose: Recent studies demonstrated reduced cardiovascular (CV) risk with gonadotropin-releasing hormone (GnRH) antagonist, yet the underlying mechanism remains undetermined. The objective of this study was to examine longitudinal changes over time in established CV related proteins among men treated with GnRH agonists vs GnRH antagonist. Materials and Methods: We performed a proteomics analysis of serum samples collected during a phase II randomized study among 80 men with advanced prostate cancer and preexisting CV disease who were randomized to receive a GnRH agonist (39) or GnRH antagonist (41) for 1 year. Serum samples were collected at baseline and at 3, 6 and 12 months following treatment, and analyzed levels of 188 proteins using the CV panel II and III of the Olink Multiplex platform (Olink Proteomics AB, Uppsala, Sweden). We fitted a linear mixed effects model to assess evidence of a treatment effect across CV related protein values. This included terms for treatment arm, protein levels and time-by-treatment interaction. Results were corrected for multiple testing using the Benjamini-Hochberg method. Results: The CV proteomics analysis included 283 samples from 78 subjects. We identified 5 proteins with distinct patterns over time depending on study arm: human chitotriosidase, macrophage receptor with collagenous structure, cathepsin D, superoxide dismutase 2 and hydroxyacid oxidase 1. All 5 are associated with plaque stability and demonstrated an increased level among subjects in the GnRH antagonist arm compared to agonist. Conclusions: We compared longitudinal changes in CV proteins among men using androgen deprivation therapy. Our results support a direct protective effect of GnRH antagonist on plaque stability rather than a hazardous consequence of GnRH agonists on plaque rupture. This is a hypothesis generating study, and requires further confirmation.