Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).

The chloramine dilemma.

A decades-long drinking-water disinfection mystery ends with a potentially toxic surprise.

Bacterial dealkylation of benzalkonium chlorides in wastewater produces benzyldimethylamine, a potent N-nitrosodimethylamine precursor.

N-nitrosodimethylamine (NDMA) is a carcinogenic disinfection byproduct that forms during chloramine disinfection of municipal wastewater effluents which are increasingly used to augment drinking water supplies due to growing water scarcity. Knowledge of wastewater NDMA precursors is limited and the known pool of NDMA precursors has not closed the mass balance between precursor loading, precursor NDMA yield, and formed NDMA. Benzalkonium chlorides (BACs) are the most prevalent quaternary ammonium surfactants and have antimicrobial properties.

Minimizing -Nitrosodimethylamine Formation During Disinfection of Blended Seawater and Wastewater Effluent.

Augmenting seawater with wastewater has the potential to reduce the energy demand and environmental impacts associated with seawater desalination. Alternatively, as wastewater reuse becomes more widespread, augmenting wastewater with seawater can increase the available water supply. However, the chemistry of disinfecting a blended stream has not been explored.

Emerging Areas in Undergraduate Analytical Chemistry Education: Microfluidics, Microcontrollers, and Chemometrics.

Analytical chemistry is a fast-paced field with frequent introduction of new techniques via research labs; however, incorporation of new techniques into academic curricula lags their adoption in research and industry. This review describes the recent educational literature on microfluidics, microcontrollers, and chemometrics in the undergraduate analytical chemistry curriculum. Each section highlights opportunities for nonexpert faculty to get started with these techniques and more advanced implementations suitable for experienced practitioners.

Immune-based therapies in diffuse large B-cell lymphoma.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and clinically heterogeneous malignancy originating from B-cells with up to 40% of patients experiencing primary refractory disease or relapse after first-line treatment. However, the past 5 years have seen a flurry of new drug approvals for DLBCL anchored upon new immune therapies, including chimeric antigen receptor (CAR) T-cells and antibody-based therapies.

Areas Covered: This article summarizes recent advances in the treatment of DLBCL, including in the first line and relapsed and refractory setting (second-line and beyond).

Chloramination of Nitromethane: Incomplete Chlorination and Unexpected Substitution Reaction.

Ozone is commonly used as a predisinfectant in potable water reuse treatment trains. Nitromethane was recently found as a ubiquitous ozone byproduct in wastewater, and the key intermediate toward chloropicrin during subsequent secondary disinfection of ozonated wastewater effluent with chlorine. However, many utilities have switched from free chlorine to chloramines as a secondary disinfectant.

Ipso Substitution of Aromatic Bromine in Chlorinated Waters: Impacts on Trihalomethane Formation.

Parabens and salicylates were examined as disinfection byproduct (DBP) precursors to explore the possible influence of ipso substitution (i.e., halogen exchange) on the yield and speciation of trihalomethanes (THMs) formed during water chlorination.

CAR T-cells and macrophages in large B-cell lymphoma: impact on toxicity and efficacy.

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is the current standard of care for the treatment of relapsed refractory large B cell lymphoma, demonstrating impressive response rates in the second- and third-line setting. Despite these advances, this treatment strategy can result in significant toxicities, such as cytokine release syndrome or immune effector cell associated neurotoxicity syndrome. While the exact mechanisms of these immune-mediated toxicities are not clearly understood, emerging pre-clinical and clinical studies have revealed the pivotal role of myeloid cells, particularly macrophages, as key contributors to the efficacy of treatments and as crucial mediators of toxicity.

Out of Thin Air? Catalytic Oxidation of Trace Aqueous Aldehydes with Ambient Dissolved Oxygen.

Water reuse is expanding due to increased water scarcity. Water reuse facilities treat wastewater effluent to a very high purity level, typically resulting in a product water that is essentially deionized water, often containing less than 100 μg/L organic carbon. However, recent research has found that low-molecular-weight aldehydes, which are toxic electrophiles, comprise a significant fraction of the final organic carbon pool in recycled wastewater in certain treatment configurations.

Ozonation of organic compounds in water and wastewater: A critical review.

Ozonation has been applied in water treatment for more than a century, first for disinfection, later for oxidation of inorganic and organic pollutants. In recent years, ozone has been increasingly applied for enhanced municipal wastewater treatment for ecosystem protection and for potable water reuse. These applications triggered significant research efforts on the abatement efficiency of organic contaminants and the ensuing formation of transformation products.

Antibiotic transformation in an anaerobic membrane bioreactor linked to membrane biofilm microbial activity.

Although extensive research to date has focused on enhancing removal rates of antibiotics from municipal wastewaters, the transformation products formed by anaerobic treatment processes remain understudied. The present work aims to examine the possible roles that the different microbial communities of an anaerobic membrane bioreactor (AnMBR) play in the transformation of antibiotics during wastewater treatment. As part of this work, sulfamethoxazole, erythromycin, and ampicillin were added in separate stages to the influent of the AnMBR at incremental concentrations of 10, 50, and 250 μg/L each.

Formation and Fate of Nitromethane in Ozone-Based Water Reuse Processes.

Ozonation is widely used in wastewater reclamation treatment trains, either for micropollutant control or as a disinfectant and preoxidant in certain reuse processes. We recently found that ozonation of secondary effluent produces nitromethane, which can be efficiently transformed to genotoxic halonitromethanes by chlorination. In this work, the fate of nitromethane through water reuse treatment trains was characterized by analyzing samples from five reuse operations employing ozone.

Neoadjuvant Pembrolizumab and High-Dose IFNα-2b in Resectable Regionally Advanced Melanoma.

Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma.

Patients And Methods: Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.

Evaluation of Histidine Reactivity and Byproduct Formation during Peptide Chlorination.

The covalent modifications resulting from chlorine reactions with peptide-bound amino acids contribute to pathogen inactivation and disinfection byproduct (DBP) formation. Previous research suggested that histidine is the third most reactive of the seven chlorine-reactive amino acids, leading to the formation of 2-chlorohistidine, 2-oxohistidine, or low-molecular-weight byproducts such as trihalomethanes. This study demonstrates that histidine is less reactive toward formation of chlorine transformation products (transformation time scale of hours to days) than five of the seven chlorine-reactive amino acids, including tyrosine (transformation time scale of minutes).

Transformation of -Methylamine Drugs during Wastewater Ozonation: Formation of Nitromethane, an Efficient Precursor to Halonitromethanes.

Potable reuse of wastewater is expanding, and ozonation for water reuse is becoming more common, either as a preoxidant before membranes or as part of ozone/biological activated carbon (O/BAC) systems. However, previous research has demonstrated that ozone drastically increases the formation potential of genotoxic halonitromethanes (HNMs), including during O/BAC. Chloropicrin, the most common HNM, is synthesized by chlorinating nitromethane, suggesting that nitromethane may be the immediate precursor of chloropicrin, although nitromethane is unlikely to occur naturally in wastewater.

Summation of disinfection by-product CHO cell relative toxicity indices: sampling bias, uncertainty, and a path forward.

The cyto- and genotoxic potencies of disinfection by-products (DBPs) have been evaluated in published literature by measuring the response of exposed Chinese hamster ovary cells. In recent publications, DBP concentrations divided by their individual toxicity indices are summed to predict the relative toxicity of a water sample. We hypothesized that the omission or inclusion of certain DBPs over others is equivalent to statistical sampling bias and may result in biased conclusions.

Assessment of inpatient psychiatric readmission risk among patients discharged on an antipsychotic polypharmacy regimen: A retrospective cohort study.

Objective: Patients are frequently prescribed multiple antipsychotic medications, leading to higher healthcare costs and increased risk for side effects. The efficacy of multiple versus single antipsychotics to prevent acute relapse, measured by incidence of inpatient readmission, is investigated in Arizona, USA.

Method: A retrospective chart review compared socio-demographic and clinical data from 1,010 patients discharged on a single and 377 discharged on multiple antipsychotic medications.

Reverse Osmosis Shifts Chloramine Speciation Causing Re-Formation of NDMA during Potable Reuse of Wastewater.

UV-based advanced oxidation processes (AOPs) effectively degrade N-nitrosodimethylamine (NDMA) passing through reverse osmosis (RO) units within advanced treatment trains for the potable reuse of municipal wastewater. However, certain utilities have observed the re-formation of NDMA after the AOP from reactions between residual chloramines and NDMA precursors in the AOP product water. Using kinetic modeling and bench-scale RO experiments, we demonstrate that the low pH in the RO permeate (∼5.

Assessment of Two Solid Anaerobic Digestate Soil Amendments for Effects on Soil Quality and Biosolarization Efficacy.

Anaerobic digestion is an organic waste bioconversion process that produces biofuel and digestates. Digestates have potential to be applied as soil amendment to improve properties for crop production including phytonutrient content and pest load. Our objective was to assess the impact of solid anaerobic digestates on weed seed inactivation and soil quality upon soil biosolarization (a pest control technique that combines solar heating and amendment-induced microbial activity).

Electrolyte Gradient-Based Modulation of Molecular Transport through Nanoporous Gold Membranes.

Nanopores, and nanoporous materials in general, are interesting for applications in chemical and biomolecular transport as pore sizes are on the same scale as the dimension of many (bio)chemical species. Many studies have focused on either single pores or small arrays of cylindrical pores, which are convenient in terms of their amenability toward computational modeling of transport phenomenon. However, the limited overall porosity may inhibit transport flux as well as the eventual implementation of these materials as active separation elements.

Surrogate in vitro activation of innate immunity synergizes with interleukin-7 to unleash rapid antigen-driven outgrowth of CD4+ and CD8+ human peripheral blood T-cells naturally recognizing MUC1, HER2/neu and other tumor-associated antigens.

Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion.