Endemic Burkitt lymphoma (eBL) is one of the most prevalent cancer in children in sub-Saharan Africa, and while prior studies have found that Epstein-Barr virus (EBV) type and variation may alter the tumor driver genes necessary for tumor survival, the precise relationship between EBV variation and EBV-associated tumorigenesis remains unclear due to lack of scalable, cost-effective, viral whole-genome sequencing from tumor samples. This study introduces a rapid and cost-effective method of enriching, sequencing, and assembling accurate EBV genomes in BL tumor cell lines through a combination of selective whole genome amplification (sWGA) and subsequent 2-tube multiplex polymerase chain reaction along with long-read sequencing with a portable sequencer. The method was optimized across a range of parameters to yield a high percentage of EBV reads and sufficient coverage across the EBV genome except for large repeat regions.
View Article and Find Full Text PDFAlthough Epstein-Barr virus (EBV) plays a role in Burkitt lymphoma (BL) tumorigenesis, it is unclear if EBV genetic variation impacts clinical outcomes. From 130 publicly available whole-genome tumor sequences of EBV-positive BL patients, we used least absolute shrinkage and selection operator (LASSO) regression and Bayesian variable selection models within a Cox proportional hazards framework to select the top EBV variants, putative driver genes, and clinical features associated with patient survival time. These features were incorporated into survival prediction and prognostic subgrouping models.
View Article and Find Full Text PDFBackground: Access to deceased donor kidney transplantation may be restricted in the event of resource limitation induced by extreme peaks in activity or local major incidents, which exceed centre capacity. An organ-sharing protocol was developed by the five London transplant units in 2019 to establish a system for safe transfer of organs and recipients between five regional kidney transplant units. We describe the activity and outcomes over the initial 20-month period.
View Article and Find Full Text PDFBackground And Objective: As most Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions on MRI harbor Gleason grade (GG) group ≥2 disease on biopsy, optimal management of patients with imaging-biopsy discordance remains unclear. To estimate grade misclassification, we evaluated the incidence of Gleason upgrading among patients with GG1 disease in the setting of a PI-RADS 5 lesion.
Methods: We conducted a single-institution retrospective analysis to identify patients with GG1 prostate cancer on fusion biopsy with MRI demonstrating ≥1 PI-RADS 5 lesion.
Radiation- (radio-)recurrent prostate cancer poses a significant challenge in clinical management due to its complexity and varied treatment responses. The recurrence of prostate cancer following radiotherapy necessitates a nuanced management strategy that considers disease stage and aggressiveness, patient health status, and prior treatment modalities. Androgen deprivation therapy (ADT), a cornerstone in the management of regional or distant relapse, often initiates the therapeutic cascade, effectively suppressing tumor growth by targeting androgen signaling.
View Article and Find Full Text PDFJ Chem Theory Comput
December 2024
Many quantum algorithms rely on a quality initial state for optimal performance. Preparing an initial state for specific applications can considerably reduce the cost of probabilistic algorithms such as the well studied quantum phase estimation (QPE). Fortunately, in the application space of quantum chemistry, generating approximate wave functions for molecular systems is well studied, and quantum computing algorithms stand to benefit from importing these classical methods directly into a quantum circuit.
View Article and Find Full Text PDFObjective: To study the impact of a student-specific urology conference for students considering a career in urology. The first symposium specifically for medical students interested in urology was designed to provide an opportunity to present their research, explore urological subspecialties, and network with faculty members, residents, and other students.
Methods: Medical students and faculty at a US medical school organized the inaugural New England Student Urology Symposium (NESUS).
Oncol Lett
January 2025
Prostate-specific antigen (PSA) remains a key biomarker for the diagnosis and monitoring of prostate cancer (PCa). For patients within the 'PSA gray zone', the positive predictive value (PPV) of PSA for PCa detection by biopsy is estimated to be between 30 and 42%. In the present study, a single-center, retrospective, evaluator-blinded, pilot and pivotal clinical trial was performed to assess the clinical performance of the mirCaP kit (Urotech, Inc.
View Article and Find Full Text PDFImportance: Although prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown.
Objective: To estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer.
Design, Setting, And Participants: This decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy.
Importance: The Prostate Imaging Reporting & Data System (PI-RADS) scoring guidelines were developed to address the substantial variation in interpretation and reporting of prostate cancer (PCa) multiparametric MRI (mpMRI) results, and subsequent updates have sought to further improve inter-reader reliability. Nonetheless, the variability of PI-RADS scoring in real-world settings may represent a continuing challenge to the widespread standardization of prostate mpMRI and limit its overall clinical benefit.
Objective: To assess variability in mpMRI interpretation and reporting of PCa, we evaluated the discrepancies in PI-RADS scoring between community practices and a tertiary academic care center.
Most malaria rapid diagnostic tests (RDTs) detect histidine-rich protein 2 (PfHRP2) and PfHRP3, but deletions of and genes make parasites undetectable by RDTs. We analyzed 19,313 public whole-genome-sequenced field samples to understand these deletions better. deletion only occurred by chromosomal breakage with subsequent telomere healing.
View Article and Find Full Text PDFThe aim of this study was to explore the epidemiology of cutaneous malignant melanoma (CMM) and the associated risk factors influencing its occurrence and survival among Koreans aged <20 years. In this retrospective cohort investigation, we identified cases of incident melanoma diagnosed in Korean patients aged 0-19 years between 2004 and 2019, utilizing the National Health Insurance database. We assessed annual fluctuations in age-adjusted incidence rates and examined 5-year survival rates based on various factors, including sex, age, income level, sun-exposed sites, and the Charlson Comorbidity Index.
View Article and Find Full Text PDFIntroduction: Although the clinical benefits of pelvic lymph node dissection (PLND) at the time of radical prostatectomy for prostate cancer remain uncertain, major guidelines recommend PLND based on risk profile. Thus, the objective of this study was to examine the association between PLND and survival among patients undergoing RP stratified by Gleason grade group (GG) with the aim of allowing patients and physicians to make more informed care decisions about the potential risks and benefits of PLND.
Materials And Methods: From the SEER-17 database, we examined overall (OS) and prostate cancer-specific (PCSS) survival of prostate cancer patients who underwent RP from 2010 to 2015 stratified by GG.
Prostate specific antigen (PSA) has transformed the diagnosis and treatment of prostate cancer by enabling early detection at global scale. Due to expression in both benign and malignant cells, PSA-based prostate cancer screening using single cut-points yields imperfect diagnostic performance and has led to the detection and over-treatment of low-grade prostate cancer. Additional challenges in the interpretation of PSA include substantial inter and intrapersonal variation, differences with age and prostate volume, and selection of standardized PSA value cutoffs for clinical application.
View Article and Find Full Text PDFA new concept for the synthesis of dialkyl chloronium cations [R-Cl-R] is described (R=CH, CHCF), that allows the formation of fluorinated derivatives. By utilizing the xenonium salt [XeOTeF][M(OTeF)] (M=Sb, n=6; M=Al, n=4) chlorine atoms of chloroalkanes or the deactivated chlorofluoroalkane CHClCF are oxidized and removed as ClOTeF leading to the isolation of the corresponding chloronium salt. Since the resulting highly electrophilic cation [Cl(CHCF)] is able to alkylate weak nucleophiles, this compound can be utilized for the introduction of a fluorinated alkyl group to those.
View Article and Find Full Text PDFNon-small-cell lung cancer (NSCLC) with concurrent mutations in KRAS and the tumour suppressor LKB1 (KL NSCLC) is refractory to most therapies and has one of the worst predicted outcomes. Here we describe a KL-induced metabolic vulnerability associated with serine-glycine-one-carbon (SGOC) metabolism. Using RNA-seq and metabolomics data from human NSCLC, we uncovered that LKB1 loss enhanced SGOC metabolism via serine hydroxymethyltransferase (SHMT).
View Article and Find Full Text PDFBackground: Breast reconstruction is an integral postoncologic procedure that has been associated with improved mental health and psychological outcomes. The possible interaction between existing psychiatric diagnoses hospital courses and postoperative complications warrants further exploration.
Methods: Bilateral breast reconstruction patients were identified from the 2016 to 2018 Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP - NIS).
Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs.
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