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Hak J Lee,1 Kasra Yousefi,2 Zaid Haddad,2 Firas Abdollah,3 Lucia LC Lam,2 Heesun Shin,2 Mohammed Alshalalfa,2 Elana Godebu,1 Song Wang,4 Ahmed Shabaik,5 Elai Davicioni,2 Christopher J Kane1 1Department of Urology, University of California, San Diego, San Diego, CA, USA; 2GenomeDx Biosciences Inc., Vancouver, BC, Canada; 3Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, 4UC San Diego Health System, San Diego, CA, 5Department of Pathology, University of California, San Diego, San Diego, CA, USA Objective: To evaluate the performance of the Decipher test in predicting lymph node invasion (LNI) on radical prostatectomy (RP) specimens. Methods: We identified 1,987 consecutive patients with RP who received the Decipher test between February and August 2015 (contemporary cohort). In the contemporary cohort, only the Decipher score from RP specimens was available for analysis. In addition, we identified a consecutive cohort of patients treated with RP between 2006 and 2012 at the University of California, San Diego, with LNI upon pathologic examination (retrospective cohort). The retrospective cohort yielded seven, 22, and 18 tissue specimens from prostate biopsy, RP, and lymph nodes (LNs) for individual patients, respectively. Univariable and multivariable logistic regression analyses were used to evaluate the performance of Decipher in the contemporary cohort with LNI as the endpoint. In the retrospective cohort, concordance of risk groups was assessed using validated cut-points for low (0.60) Decipher scores. Results: In the contemporary cohort, 51 (2.6%) patients had LNI. Decipher had an odds ratio of 1.73 (95% confidence interval, 1.46–2.05) and 1.42 (95% confidence interval, 1.19–1.7) per 10% increase in score on univariable and multivariable (adjusting for pathologic Gleason score, extraprostatic extension, and seminal vesicle invasion), respectively. No significant difference in the clinical and pathologic characteristics between the LN positive patients of contemporary and retrospective cohorts was observed (all P>0.05). Accordingly, among LN-positive patients in the contemporary cohort and retrospective cohort, 80% and 77% had Decipher high risk scores (P=1). In the retrospective cohort, prostate biopsy cores with the highest Gleason grade and percentage of tumor involvement had 86% Decipher risk concordance with both RP and LN specimens. Conclusion: Decipher scores were highly concordant between pre- and post-surgical specimens. Further, Decipher scores from RP tissue were predictive of LNI at RP. If validated in a larger cohort of prostate biopsy specimens for prediction of adverse pathology at RP, Decipher may be useful for improved pre-operative staging. Keywords: prostate, biopsy, lymph node invasion, genomic classifier, radical prostatectomy, decipher, prognosis

BackgroundCurrently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics.MethodsDe-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed. For clinical testing, tumor specimen from the highest Gleason grade was sampled using a 1.5 mm tissue punch. Decipher scores were calculated based on a previously locked model. Correlations between Decipher score and clinicopathologic variables were computed using Spearman's rank correlation. Mixed-effect linear models were used to study the association of practice type and Decipher score. The significance level was 0.05 for all tests.ResultsDecipher score had a positive correlation with pathologic Gleason score (PGS; r=0.37, 95% confidence interval (CI) 0.34-0.41), pathologic T-stage (r=0.31, 95% CI 0.28-0.35), CAPRA-S (r=0.32, 95% CI 0.28-0.37) and patient age (r=0.09, 95% CI 0.05-0.13). Decipher reclassified 52%, 76% and 40% of patients in CAPRA-S low-, intermediate- and high-risk groups, respectively. We detected a 28% incidence of high-risk disease through the Decipher score in pT2 patients and 7% low risk in pT3b/pT4, PGS 8-10 patients. There was no significant difference in the Decipher score between patients from community centers and those from academic centers (P=0.82).ConclusionsAlthough Decipher correlated with baseline tumor characteristics for over 2 000 patients, there was significant reclassification of tumor aggressiveness as compared to clinical parameters alone. Utilization of the Decipher genomic classifier can have major implications in assessment of postoperative risk that may impact physician-patient decision making and ultimately patient management.

The application of the high-order accurate schemes with multi-block domains is essential in problems with complex geometries. Primarily, accurate block-interface treatment is found to be of significant importance for precisely capturing discontinuities in such complex configurations. In the current study, a conservative and accurate multi-block strategy is proposed and implemented for a high-order compact finite-difference solver. For numerical discretization, the Beam-Warming linearization scheme is used and further extended for three-dimensional problems. Moreover, the fourth-order compact finite-difference scheme is employed for spatial discretization. The capability of the high-order multi-block approach is then evaluated for the onedimensional flow inside a Shubin nozzle, two-dimensional flow over a circular bump, and three-dimensional flow around a NACA 0012 airfoil. The results showed a reasonable agreement with the available exact solutions and simulation results in the literature. Further, the proposed block-interface treatment performed quite well in capturing shock waves, even in situations that the location of the shock coincides with block interfaces. [ABSTRACT FROM AUTHOR]

Titanium-45 with a half-life of 3.09 hours decays by emission of positrons (85%) and the electron capture process (15%). These properties make this radionuclide useful in the diagnosis of tumors by positron emission tomography. In this study, after having considered the excitation functions for the 45Sc(p, n)45Ti reaction using TALYS and ALICE/ASH codes and after the comparison with other experimental data, 45Ti was produced by dint of the pressing method and a newly designed and manufactured shuttle and capsule, resulting in an experimental yield of 403.3 MBq/mAh. Essential target thickness and physical yield were calculated. The scandium oxide target was irradiated at a 20 mA current and a 21 MeV proton beam energy for 1 hour.

Two new cadmium-containing Wells-Dawson polyoxometalates K8[α1-P2W17Cd(OH2)O61]•16H2O (α1-P2W17Cd) and K8[α2-P2W17Cd(OH2) O61]•16H2O (α2-P2W17Cd) were synthesized as aqueous soluble potassium salts. The cadmium-substituted complexes have been characterized by IR, 31P NMR, 113Cd NMR spectroscopy and cyclic voltametry (CV). Redox activities for the tungsten and cadmium centers have been observed by using cyclic voltammetry. It was found that the presence of cadmium decreases the electrocatalytic activity of the [α1-LiP2W17O61]9- and α2-[P2W17O61]10-heteropolyanions.

RNA structural switches are key regulators of gene expression in bacteria, but their characterization in Metazoa remains limited. Here, we present SwitchSeeker, a comprehensive computational and experimental approach for systematic identification of functional RNA structural switches. We applied SwitchSeeker to the human transcriptome and identified 245 putative RNA switches. To validate our approach, we characterized a previously unknown RNA switch in the 3' untranslated region of the RORC (RAR-related orphan receptor C) transcript. In vivo dimethyl sulfate (DMS) mutational profiling with sequencing (DMS-MaPseq), coupled with cryogenic electron microscopy, confirmed its existence as two alternative structural conformations. Furthermore, we used genome-scale CRISPR screens to identify trans factors that regulate gene expression through this RNA structural switch. We found that nonsense-mediated messenger RNA decay acts on this element in a conformation-specific manner. SwitchSeeker provides an unbiased, experimentally driven method for discovering RNA structural switches that shape the eukaryotic gene expression landscape., (© 2024. The Author(s).)

MicroRNAs (miRs) play a crucial role in the leukemogenesis and the prognosis of acute myeloid leukemia (AML). This study investigated the therapeutic effects of resveratrol, gallic acid, and piperine as natural anticancer agents on the HL-60 cell line and their roles in apoptosis. In this experimental study, quantitative analysis of miRs, including miR-17, miR-92b, miR-181a, and miR-222, were performed in 150 newly diagnosed patients with AML by real-time PCR assay. HL-60 cell viability as well as the expression of miRs, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA, were also assessed after transfection with the LNA-miRs and treatment with resveratrol, gallic acid, and piperine. The expression of miR-17 and miR-181a decreased significantly in LNA-anti-miRs. Although HL-60 cell viability decreased in LNA-anti-miR-222, miR-17, and miR-92b, blockade of miR-181a increased the cell viability. Besides, the cell viability increased merely in the piperine-treated group. Compared to untreated cells, miR-17 and miR-92b expression significantly increased in gallic acid- and resveratrol-treated cells. In HL-60 cells treated with resveratrol, gallic acid, and piperine, the expression of miR-181a was also increased significantly. The expression of BAX was also increased in resveratrol and piperine-treated groups. Compared to untreated cells, the expression of c-Kit increased significantly in the piperine-treated group; however, it decreased in the resveratrol-treated group. LNA-anti-miRs may be a promising agent for the treatment of AML. All three compounds used in this study showed anticancer effects, which can exert the desired outcome in patients with AML., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Incipient carious lesions, the most common complication in orthodontic patients with fixed appliances, call for the development of novel preventive dental materials that do not rely on patient adherence. The present study aimed to assess the ability of elastomeric ligatures coated with bacterial nanocellulose (BNC) to deliver sustained antibacterial activity, during the standard 28-day interval between orthodontic appointments, without compromising their mechanical properties. Kombucha membrane was used to produce cellulose as a secondary product from the fermentation of tea broth with symbiotic bacteria and yeast culture. Characterization of BNC-coated elastomeric ligatures was performed using Fourier Transform Infrared Spectroscopy and Energy Dispersive Spectroscopy analysis. The samples were pre-treated by immersion first in isopropyl alcohol, then in 8 mL nanocellulose solution for 7 days. Tensile strain and strength of the BNC-coated and conventional ligatures were evaluated using a tensile testing machine. Direct contact and agar diffusion tests were performed to assess the antibacterial activity of nanocellulose. In addition, the release profile of BNC was evaluated. Data analysis was performed by one-way analysis of variance (ANOVA) followed by post-hoc Tukey's test and Wilcoxon signed-rank test. P values less than 0.05 was regarded as significant. There was no statistically significant difference in tensile strain and strength between the BNC-coated and conventional ligatures. The coated ligatures provided sustained antibacterial activity during the required 28 days. The use of BNC-coated elastomeric ligatures in patients with fixed orthodontic appliances might be a promising solution to plaque formation and subsequent enamel decalcification., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Eskandari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aims of current investigation were to study the growth performance, carcass traits, meat quality and expression profile of Myostatin ( MSTN ), Insulin-like growth factor-1 ( IGF-I ), Myogenin ( MyoG ) and Myogenic regulatory factor 4 ( MRF4 ) genes in three commercial broiler strains including Ross (Ross 308), Cobb (Cobb 500), and Arian in 2023. A total number of 240 one-day-old chicks were reared under an equalized standard management condition for 6 weeks. Performance, organ weights, meat quality and the expression level of the myogenic genes in the pectoral muscle were investigated. The lowest body weight (BW), feed intake, weight gain and highest feed conversion ratio (FCR) was observed for Arian at the end of the study. The meat quality was similar between strains. The IGF-I expression level was significantly higher on 42 days of age in Cobb compared to Ross and Arian. The MRF4 expression level was significantly higher on 28 days of age in Cobb compared to Ross. The MyoG expression level was significantly lower in Arian compared to Cobb on 42 days of age. Furthermore, the MSTN expression level was significantly lower in Cobb compared to Ross and Arian on 42 days of age. The remarkable differences in gene expression levels at the end of the rearing period was supported by higher growth performance and BW of Cobb compared to Ross and Arian strains. In conclusion, the findings of current study could conveniently help assess the performance of these broiler strains under similar rearing condition., Competing Interests: The authors declare no conflict of interest., (© 2024 Urmia University. All rights reserved.)

Ganoderma lucidum methanolic extract (GLME) has attracted tremendous attention due to its exceptional antimicrobial and anticancer properties that can be delicately tuned by controlling the initial extraction's content and concentration. Herein, we detailed the characterization, antimicrobial, and cytotoxic performance of GLME as a potential multi-functional therapeutic agent. Accordingly, FTIR, XRD, FESEM, EDX, and HPLC analyses were employed to assess the samples, followed by disc diffusion and microdilution broth methods to test its antibacterial effects against four Gram-positive and Gram-negative bacterial strains, viz., Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. MTT assay was applied to determine the cytotoxic activity of GLME against PDL and Hek-293 normal cell lines and MCF-7 and K-562 cancer cell lines. The IC50 values of 598 µg mL -1 and 291 µg mL -1 were obtained for MCF-7 and K-562 cancer cell lines, which confirmed the stronger anticancer activity of the GLME against blood cancer cells than breast cancer cells. This is while the IC50 of normal Hek-293 cells is 751 µg mL -1 , and the lowest toxicity was observed for normal PDL cells with more than 57% survival at a concentration of 3000 µg mL -1 . The results showed that the antibacterial property of this product against E.coli bacteria was higher than streptomycin, so the zone of inhibition was observed as 44 ± 0.09 mm and 30 ± 0.11 mm, respectively. These data provide valuable insights into the therapeutic usage of GLME for treating breast and blood cancers. This work is motivated by research studies looking for pharmacological products to address chronic and acute diseases, where further resources and studies are required to explore such products' adverse effects and toxicity., (© 2023. Springer Nature Limited.)

Background: Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects., Methods: Antibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL)., Results: Three different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model., Conclusion: This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma in vitro and in vivo ., Competing Interests: MP, KI, DM, SS and CH are employees of MorphoSys AG, KL, SS and JE own MorphoSys AG stocks. MP, JE and SS hold MorphoSys AG patents. This study received funding from MorphoSys AG. The funder was involved in study design, collection, analysis, interpretation of the data, writing of this article and decision to submit it for publication., (Copyright © 2023 Patra-Kneuer, Chang, Xu, Augsberger, Grau, Zapukhlyak, Ilieva, Landgraf, Mangelberger-Eberl, Yousefi, Berning, Kurz, Ott, Klener, Khandanpour, Horna, Schanzer, Steidl, Endell, Heitmüller and Lenz.)