Quantification of Particle-Associated Viruses in Secondary Treated Wastewater Effluent.

Viruses can interact with a broad range of inorganic and organic particles in water and wastewater. These associations can protect viruses from inactivation by quenching chemical disinfectants or blocking ultraviolet light transmission, and a much higher dosage of disinfectants is required to inactivate particle-associated viruses than free viruses. There have been only few studies of the association of viruses with particles in wastewater, particularly in secondary treated effluent.

Somatic mitochondrial DNA mutations are a source of heterogeneity among primary leukemic cells.

Somatic mitochondrial DNA (mtDNA) mutations are prevalent in tumors, yet defining their biological significance remains challenging due to the intricate interplay between selective pressure, heteroplasmy, and cell state. Utilizing bulk whole-genome sequencing data from matched tumor and normal samples from two cohorts of pediatric cancer patients, we uncover differences in the accumulation of synonymous and nonsynonymous mtDNA mutations in pediatric leukemias, indicating distinct selective pressures. By integrating single-cell sequencing (SCS) with mathematical modeling and network-based systems biology approaches, we identify a correlation between the extent of cell-state changes associated with tumor-enriched mtDNA mutations and the selective pressures shaping their distribution among individual leukemic cells.

A systematic review on global zoonotic virus-associated mortality events in marine mammals.

Marine mammals play a critical role as sentinels for tracking the spread of zoonotic diseases, with viruses being the primary causative factor behind infectious disease induced mortality events. A systematic review was conducted to document marine mammal mortality events attributed to zoonotic viral infections in published literature across the globe. This rigorous search strategy yielded 2883 studies with 88 meeting inclusion criteria.

Integrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials.

In this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084 ) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.

Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia.

Purpose: Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML.

Analysis of Prognostic Factors and Cancer-Specific Survival in Patients with Undifferentiated and Dedifferentiated Endometrial Carcinoma Undergoing Various Postoperative Adjuvant Therapies.

Purpose: To investigate prognostic factors affecting cancer-specific survival (CSS) and to analyze the survival outcomes of patients with undifferentiated and dedifferentiated endometrial carcinoma (UDEC) who underwent various postoperative adjuvant therapies.

Methods: The independent risk factors affecting CSS were studied using univariate and multivariate Cox regression analysis, and CSS in the presence of various postoperative treatments was evaluated using Kaplan-Meier method based on the cohort with pathologically confirmed UDEC from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, the study included 18 cases with UDEC in our center and explored their molecular characteristics and prognosis.

Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia.

Importance: Disparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their White counterparts.

Objective: To assess whether varying intensity of induction therapy to treat pediatric AML is associated with reduced disparities in treatment outcome by race.

Design, Setting, And Participants: A comparative effectiveness analysis was conducted of 86 Black and 359 White patients with newly diagnosed AML who were enrolled in the AML02 trial from 2002 to 2008 or the AML08 trial from 2008 to 2017.

Complete Laparoscopic Type C2 Radical Surgery for Cervical Stump Cancer: No-Look and No-Touch Techniques.

Background: Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus. We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC.

Methods: CLRS for six patients with CSC was performed from January 2021 to January 2022.

Dual chemodynamic/photothermal therapeutic nanoplatform based on DNA-functionalized prussian blue.

The combination of chemodynamic therapy and photothermal therapy has a promising application owing to its impressive anti-cancer effects. However, the degradability of the material and the lack of targeting severely limit its further clinical application. Herein, DNAs containing nucleolin aptamer (AS1411) and different bases sequences were used to functionalize PB NPs for the targeted treatment.

Targeted community wastewater surveillance for SARS-CoV-2 and Mpox virus during a festival mass-gathering event.

Wastewater surveillance has emerged recently as a powerful approach to understanding infectious disease dynamics in densely populated zones. Wastewater surveillance, while promising as a public health tool, is often hampered by slow turn-around times, complex analytical protocols, and resource-intensive techniques. In this study, we evaluated an affinity capture method and microfluidic digital PCR as a rapid approach to quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mpox (formerly known as monkeypox) virus, and fecal indicator, pepper mild mottle virus (PMMoV) in wastewater during a mass-gathering event.

Topotecan clearance based on a single sample and a population pharmacokinetic model: Application to a pediatric high-risk neuroblastoma clinical trial.

Background: Topotecan, an antitumor drug with systemic exposure (SE)-dependent activity against many pediatric tumors has wide interpatient pharmacokinetic variability, making it challenging to attain the desired topotecan SE. The study objectives were to update our topotecan population pharmacokinetic model, to evaluate the feasibility of determining individual topotecan clearance using a single blood sample, and to apply this approach to topotecan data from a neuroblastoma trial to explore exposure-response relationships.

Procedure: Our previous population pharmacokinetic and covariate model was updated using data from 13 clinical pediatric studies.

Temporal and spatial relationships of CrAssphage and enteric viral and bacterial pathogens in wastewater in North Carolina.

Enteric disease remains one of the most common concerns for public health, particularly when it results from human exposure to surface and recreational waters contaminated with wastewater. Characterizing the temporal and spatial variation of enteric pathogens prevalent in wastewater is critical to develop approaches to mitigate their distribution in the environment. In this study, we aim to characterize pathogen variability and test the applicability of the human-associated wastewater indicator crAssphage as an indicator of enteric viral and bacterial pathogens.

SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia.

Cytarabine arabinoside (Ara-C) has been the cornerstone of acute myeloid leukemia (AML) chemotherapy for decades. After cellular uptake, it is phosphorylated into its active triphosphate form (Ara-CTP), which primarily exerts its cytotoxic effects by inhibiting DNA synthesis in proliferating cells. Interpatient variation in the enzymes involved in the Ara-C metabolic pathway has been shown to affect intracellular abundance of Ara-CTP and, thus, its therapeutic benefit.

An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow immune microenvironment in adult and pediatric patients with AML. We characterize unique inflammation signatures in a subset of AML patients, associated with inferior outcomes.

An Image Analysis Pipeline for Quantifying the Features of Fluorescently-Labeled Biomolecular Condensates in Cells.

Biomolecular condensates are cellular organelles formed through liquid-liquid phase separation (LLPS) that play critical roles in cellular functions including signaling, transcription, translation, and stress response. Importantly, condensate misregulation is associated with human diseases, including neurodegeneration and cancer among others. When condensate-forming biomolecules are fluorescently-labeled and examined with fluorescence microscopy they appear as illuminated foci, or puncta, in cells.

64-channel label-free fluorescence detection and single-particle counting device.

A 64-channel detection system for laser-induced fluorescence (LIF) detection at the cell level is established and applied to single event counting. Generally, fluorescence detection at the cellular level requires a dyeing label to enhance the scattered light intensity for the photodetector. However, the dyeing labels, such as fluorophores, probes, and dyes, complicate sample preparation and increase cytotoxicity in the process.

Developing Indicators of Nutrient Pollution in Streams Using 16S rRNA Gene Metabarcoding of Periphyton-Associated Bacteria.

Indicators based on nutrient-biota relationships in streams can inform water quality restoration and protection programs. Bacterial assemblages could be particularly useful indicators of nutrient effects because they are species-rich, important contributors to ecosystem processes in streams, and responsive to rapidly changing conditions. Here, we sampled 25 streams weekly (12-14 times each) and used 16S rRNA gene metabarcoding of periphyton-associated bacteria to quantify the effects of total phosphorus (TP) and total nitrogen (TN).

Mutant Samd9l expression impairs hematopoiesis and induces bone marrow failure in mice.

SAMD9 and SAMD9L germline mutations have recently emerged as a new class of predispositions to pediatric myeloid neoplasms. Patients commonly have impaired hematopoiesis, hypocellular marrows, and a greater risk of developing clonal chromosome 7 deletions leading to MDS and AML. We recently demonstrated that expressing SAMD9 or SAMD9L mutations in hematopoietic cells suppresses their proliferation and induces cell death.

Olive oil classification with Laser-induced fluorescence (LIF) spectra using 1-dimensional convolutional neural network and dual convolution structure model.

Laser-induced fluorescence (LIF) spectroscopy is widely used for the analysis and classification of olive oil. This paper proposes the classification of LIF data using a specific 1-dimensional convolutional neural network (1D-CNN) model, which does not require pre-processing steps such as normalisation or denoising and can be flexibly applied to massive data. However, by adding a dual convolution structure (Dual-conv) to the model, the features of the 1-dimensional spectra are more scattered within one convolution-pooling process; thus, the classification effects are improved.

Characterizing temporal variability in streams supports nutrient indicator development using diatom and bacterial DNA metabarcoding.

Interest in developing periphytic diatom and bacterial indicators of nutrient effects continues to grow in support of the assessment and management of stream ecosystems and their watersheds. However, temporal variability could confound relationships between indicators and nutrients, subsequently affecting assessment outcomes. To document how temporal variability affects measures of diatom and bacterial assemblages obtained from DNA metabarcoding, we conducted weekly periphyton and nutrient sampling from July to October 2016 in 25 streams in a 1293 km mixed land use watershed.

A Prussian blue nanoparticles-based fluorescent nanoprobe for monitoring microRNA-92a and microRNA-21.

Since microRNA-92a (miR-92a) and microRNA-21 (miR-21) are crucial biomarkers for colorectal cancer (CRC), monitoring miR-92a and miR-21 in serum is very significant for the early diagnosis of CRC. In this work, we developed a simple and sensitive fluorescent biosensor for the detection of miR-92a and miR-21 based on the quenching ability of Prussian blue nanoparticles (PBNPs) to fluorophores. Carboxyl fluorescein (FAM)-modified ssDNA (P-92a) and Cyanine 5 (Cy5)-modified ssDNA (P-21) were completely complementary to miR-92a and miR-21 separately.

Integrated Genomic Analysis Identifies UBTF Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia.

Unlabelled: The genetics of relapsed pediatric acute myeloid leukemia (AML) has yet to be comprehensively defined. Here, we present the spectrum of genomic alterations in 136 relapsed pediatric AMLs. We identified recurrent exon 13 tandem duplications (TD) in upstream binding transcription factor (UBTF) in 9% of relapsed AML cases.

Polygenic Ara-C Response Score Identifies Pediatric Patients With Acute Myeloid Leukemia in Need of Chemotherapy Augmentation.

Purpose: To establish a patient-specific polygenic score derived from cytarabine (ara-C) pathway pharmacogenomic evaluation to personalize acute myeloid leukemia (AML) treatment.

Materials And Methods: Single nucleotide polymorphisms (SNPs) in the ara-C-pathway genes were analyzed with outcome in patients from the multicenter-AML02 trial (N = 166). Multi-SNP predictor modeling was used to develop 10-SNP Ara-C_SNP score (ACS10) using top SNPs predictive of minimal residual disease and event-free survival (EFS) from the AML02-cohort and four SNPs previously associated with ara-C triphosphate levels in the AML97 trial.