Digital Commons Network^™

Removal Of Diclofenac In Wastewater By Activated Sludge In Batch And Moving-Bed Biofilm Reactor Experiments, Keletso Chakalisa, Piriyakorn Injai, Kullapa Chanawanno, Panaya Kotchaplai, Pumis Thuptimdang

Applied Environmental Research

This study aimed to determine the diclofenac removal in wastewater by sludge taken from an operating wastewater treatment facility. Laboratory experiments were conducted in two parts: batch and moving-bed biofilm reactor (MBBR) experiments. Results from batch experiments showed that 0.1–2 mg L-1 of diclofenac could be removed more than 80% within 72 h, and the removal efficiency reduced to less than 60% for higher concentrations. The increase in the removal rate from 0.00058 to 0.16527 mg L-1 h-1 was observed when the initial diclofenac concentration increased from 0.1 to 10 mg L-1, respectively. The average first-order rate constants of 24-h …

The Role Of Bacteria And Factors Affecting The Decomposition Of Pollutants In The Biofilter Reactor: A Review, Muliyadi Muliyadi, Purwanto Purwanto, Sri Sumiyati, Sudarno Sudarno, Budiyono Budiyono, Budi Warsito, Hadiyanto Hadiyanto

Applied Environmental Research

The findings showed that several types of bacteria can help biodegrade organic pollutants, such as Comamonadacea, which can biodegrade volatile fatty acids and aromatic compounds. Proteobacteria, Bacteroidetes, and Actinobacteria can biodegrade ammonium. Burkholderiales can biodegrade ferric ions and hydrogen. Comamonas testosteroni is able to biodegrade nitrates. Pseudomonas taiwanensis, Acinetobacter guillouiae, and Klebsiella pneumoniae can reduce copper, chromium and zinc levels. Azolla biomass reduces strontium. Rhodospirillum sp. can biodegrade cadmium, mercury, lead, and nickel. Gallionella ferruginea and Leptothrix sp. can biodegrade arsenic and manganese. Gracilaria sp. can biodegrade aluminum, chromium, and zinc. Desulfovibrio sp. can …

Nonalcoholic Fatty Liver Disease Is A Risk Factor For Thiopurine Hepatotoxicity In Crohn's Disease, Alvin T George, Matthew Glover, Quazim Alayo, Maria Zulfiqar, Daniel R Ludwig, Matthew A Ciorba, Scott Mchenry, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

METHODS: In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a …

Efficacy Of Laser Interstitial Thermal Therapy For Biopsy-Proven Radiation Necrosis In Radiographically Recurrent Brain Metastases, Michael Chan, Albert H Kim, Eric Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.

METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.

RESULTS: Ninety patients met …

Necrotic Cardiac Myocytes Skew Macrophage Polarization Towards A Classically Activated Phenotype, Wenlong Jiang, Luigi Adamo, Kenji Lim, Scot J Matkovich, Sarah Evans, Cibele Rocha-Resende, Douglas L. Mann

2020-Current year OA Pubs

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide …

The History And Organization Of The Workshop On Population And Speciation Genomics, Julia M I Barth, Scott A Handley, Daniel Kintzl, Guy Leonard, Milan Malinsky, Michael Matschiner, Britta S Meyer, Walter Salzburger, Jan Stefka, Emiliano Trucchi

2020-Current year OA Pubs

With the advent of high-throughput genome sequencing, bioinformatics training has become essential for research in evolutionary biology and related fields. However, individual research groups are often not in the position to teach students about the most up-to-date methodology in the field. To fill this gap, extended bioinformatics courses have been developed by various institutions and provide intense training over the course of two or more weeks. Here, we describe our experience with the organization of a course in one of the longest-running extended bioinformatics series of workshops, the Evomics Workshop on Population and Speciation Genomics that takes place biennially in …

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Armin Ghobadi, Amanda Cashen, Et Al.

2020-Current year OA Pubs

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Small Molecule Inhibiting Microglial Nitric Oxide Release Could Become A Potential Treatment For Neuroinflammation, Philipp Jordan, Amanda Costa, Et Al.

2020-Current year OA Pubs

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or …

Hydrogen Deuterium Exchange And Other Mass Spectrometry-Based Approaches For Epitope Mapping, Prashant N Jethva, Michael L Gross

2020-Current year OA Pubs

Antigen-antibody interactions are a fundamental subset of protein-protein interactions responsible for the "survival of the fittest". Determining the interacting interface of the antigen, called an epitope, and that on the antibody, called a paratope, is crucial to antibody development. Because each antigen presents multiple epitopes (unique footprints), sophisticated approaches are required to determine the target region for a given antibody. Although X-ray crystallography, Cryo-EM, and nuclear magnetic resonance can provide atomic details of an epitope, they are often laborious, poor in throughput, and insensitive. Mass spectrometry-based approaches offer rapid turnaround, intermediate structural resolution, and virtually no size limit for the …

Relationship Between Baseline Plasma P-Tau181 And Longitudinal Changes In Cognition And Structural Brain Measures In A Cohort Of Cognitively Unimpaired Older Adults, Marcos V Pais, Chia-Ling Kuo, Beau M Ances, Julie Loebach Wetherell, Eric J Lenze, Breno S Diniz

2020-Current year OA Pubs

INTRODUCTION: Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy.

METHODS: We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults. Follow-up lasted up to 18 months. Cognitive performance assessment included memory and cognitive control. Structural brain measures included cortical thickness, which includes the AD magnetic resonance imaging (AD MRI) signature, and hippocampal volume.

RESULTS: In this cohort of CU older adults, baseline plasma p-tau181 levels were not associated with short-term changes in …

Severe Central Nervous System Demyelination In Sanfilippo Disease, Mahsa Taherzadeh, Erjun Zhang, Irene Londono, Benjamin De Leener, Sophie Wang, Jonathan D Cooper, Timothy E Kennedy, Carlos R Morales, Zesheng Chen, Gregory A Lodygensky, Alexey V Pshezhetsky

2020-Current year OA Pubs

INTRODUCTION: Chronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC

METHODS: Brain and spinal cord tissues of human MPS III patients, 6-month-old

RESULTS: Analyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains …

Defining Solute Carrier Transporter Signatures Of Murine Immune Cell Subsets, Tania Løve Aaes, Javier Burgoa Cardás, Kodi S Ravichandran

2020-Current year OA Pubs

Solute carrier (SLC) transporters are membrane-bound proteins that facilitate nutrient transport, and the movement across cellular membranes of various substrates ranging from ions to amino acids, metabolites and drugs. Recently, SLCs have gained increased attention due to their functional linkage to innate immunological processes such as the clearance of dead cells and anti-microbial defense. Further, the druggable nature of these transporters provides unique opportunities for improving outcomes in different immunological diseases. Although the SLCs represent the largest group of transporters and are often identified as significant hits in omics data sets, their role in immunology has been insufficiently explored. This …

The Actin-Bundling Protein, Pls3, Is Part Of The Mechanoresponsive Machinery That Regulates Osteoblast Mineralization, Samantha M Chin, Carmela Unnold-Cofre, Teri Naismith, Silvia Jansen

2020-Current year OA Pubs

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During …

Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Dabeeru C Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M. Willems, Ping An, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.

Aromatic Amino Acid Metabolites Alter Interferon Signaling And Influenza Pathogenesis, Gautam Anand, Colin Clark-Dinovo, Alexandra M Perry, Victoria M Goodwin, Emma St Raymond, Sonia Sakleshpur, Ashley L Steed

2020-Current year OA Pubs

The ability of gut microbial metabolites to influence the host is increasingly recognized. The microbiota extensively metabolizes the three aromatic amino acids, tryptophan, tyrosine, and phenylalanine. Previously we have found that a metabolite of tyrosine, 4-OH-phenylpropionic acid, can enhance type I interferon (IFN) signaling and protect from influenza pathogenesis in a murine model. Herein we screened 17 related aromatic amino acid metabolites for effects on IFN signaling in human lung epithelial cells and monocytes alone and in the presence of IFN-β, influenza, and LPS. While the tryptophan family metabolites reduced IFN signaling in both cell types, the tyrosine and phenylalanine …

Safety And Efficacy Of Mca‐M2 Thrombectomy In Delayed Time Window: A Propensity Score Analysis From The Star Registry, Kaustubh Limaye, Joshua Osbun, Et Al.

2020-Current year OA Pubs

No abstract provided.

Therapeutic Activity Of Lipoxin A4 In Tio2-Induced Arthritis In Mice: Nf-Κb And Nrf2 In Synovial Fluid Leukocytes And Neuronal Trpv1 Mechanisms, Telma Saraiva-Santos, Tiago H Zaninelli, Felipe A Pinho-Ribeiro, Et Al.

2020-Current year OA Pubs

BACKGROUND: Lipoxin A4 (LXA

METHODS: Mice were stimulated with TiO

RESULTS: LXA

CONCLUSION: LXA

T-Cell Redirecting Therapies For B-Cell Non-Hodgkin Lymphoma: Recent Progress And Future Directions, David A Russler-Germain, Armin Ghobadi

2020-Current year OA Pubs

Several key advances in the treatment of B-cell non-Hodgkin lymphoma (B-NHL) over the past two decades have strategically exploited B-cell lineage markers suitable for targeting by immunotherapies. First, the addition of the anti-CD20 monoclonal antibody (mAb) rituximab to a range of standard therapies conferred remarkable outcomes improvements in diverse settings, perhaps most prominently an overall survival advantage in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Subsequently, multiple chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have revolutionized the treatment of relapsed/refractory (rel/ref) DLBCL and are active in other B-NHL subtypes as well. Most recently, the longstanding aspiration to exploit patients' …

Locus Specific Endogenous Retroviral Expression Associated With Alzheimer's Disease, Tyson Dawson, Uzma Rentia, Jessie Sanford, Carlos Cruchaga, John S K Kauwe, Keith A Crandall

2020-Current year OA Pubs

INTRODUCTION: Human endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer's disease.

METHODS: We combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer's disease and 45 healthy controls. We use telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis.

RESULTS: We identify differentially expressed genes and differentially expressed HERVs in Alzheimer's disease patients. Differentially expressed HERVs are scattered throughout the genome; many of them are members of the HERV-K superfamily. A number of HERVs are correlated …

Toward A Computational Theory Of Manifold Untangling: From Global Embedding To Local Flattening, Xin Li, Shuo Wang

2020-Current year OA Pubs

It has been hypothesized that the ventral stream processing for object recognition is based on a mechanism called cortically local subspace untangling. A mathematical abstraction of object recognition by the visual cortex is how to untangle the manifolds associated with different object categories. Such a manifold untangling problem is closely related to the celebrated kernel trick in metric space. In this paper, we conjecture that there is a more general solution to manifold untangling in the topological space without artificially defining any distance metric. Geometrically, we can either

A Novel Dual Nlrp1 And Nlrp3 Inflammasome Inhibitor For The Treatment Of Inflammatory Diseases, Callum Ah Docherty, Anuruddika J Fernando, Sarah Rosli, Maggie Lam, Roland E Dolle, Manuel A Navia, Ronald Farquhar, Danny La France, Michelle D Tate, Christopher K Murphy, Adriano G Rossi, Ashley Mansell

2020-Current year OA Pubs

OBJECTIVES: Inflammasomes induce maturation of the inflammatory cytokines IL-1β and IL-18, whose activity is associated with the pathophysiology of a wide range of infectious and inflammatory diseases. As validated therapeutic targets for the treatment of acute and chronic inflammatory diseases, there has been intense interest in developing small-molecule inhibitors to target inflammasome activity and reduce disease-associated inflammatory burden.

METHODS: We examined the therapeutic potential of a novel small-molecule inhibitor, and associated derivatives, termed ADS032 to target and reduce inflammasome-mediated inflammation

RESULTS: We describe ADS032 as the first dual NLRP1 and NLRP3 inhibitor. ADS032 is a rapid, reversible and stable inflammasome …

Identification Of Prok2 Gene Polymorphisms As Predictors Of Methamphetamine Use Disorder Risk And Indicators Of Craving Scale In The Chinese Han Population, Zhao Jiang, Tianxiao Zhang, Wei Han, Jing Xiao, Wenpei Zhang, Xiaochen Wang, Jianing Liu, Ying Yang, Congying Yang, Fanglin Guan, Tao Li, John P Rice

2020-Current year OA Pubs

No abstract provided.

Non-Canonical Functions Of Ezh2 In Cancer, Sarah M Zimmerman, Phyo Nay Lin, George P Souroullas

2020-Current year OA Pubs

Mutations in chromatin modifying genes frequently occur in many kinds of cancer. Most mechanistic studies focus on their canonical functions, while therapeutic approaches target their enzymatic activity. Recent studies, however, demonstrate that non-canonical functions of chromatin modifiers may be equally important and therapeutically actionable in different types of cancer. One epigenetic regulator that demonstrates such a dual role in cancer is the histone methyltransferase EZH2. EZH2 is a core component of the polycomb repressive complex 2 (PRC2), which plays a crucial role in cell identity, differentiation, proliferation, stemness and plasticity. While much of the regulatory functions and oncogenic activity of …

Assessment Of Antibodies In The Upper And Lower Human Respiratory Tract At Steady State And After Respiratory Viral Infection, Marios Koutsakos, Jackson S Turner, M Cristina Vazquez Guillamet, Daniel Reynolds, Tingting Lei, Derek E Byers, Ali H Ellebedy, Philip A Mudd

2020-Current year OA Pubs

OBJECTIVES: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings.

METHODS: We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were …

Role Of Cardiopulmonary Interactions In Development Of Ventilator-Induced Lung Injury-Experimental Evidence And Clinical Implications, Neel Shah, Bhushan H Katira

2020-Current year OA Pubs

Ventilator-induced lung injury (VILI) impacts outcomes in ARDS and optimization of ventilatory strategies improves survival. Decades of research has identified various mechanisms of VILI, largely focusing on airspace forces of plateau pressure, tidal volume and driving pressure. Experimental evidence indicates the role of adverse cardiopulmonary interaction during mechanical ventilation, contributing to VILI genesis mostly by modulating pulmonary vascular dynamics. Under passive mechanical ventilation, high transpulmonary pressure increases afterload on right heart while high pleural pressure reduces the RV preload. Together, they can result in swings of pulmonary vascular flow and pressure. Altered vascular flow and pressure result in increased vascular …

Multi-Omic Analysis Of The Tumor Microenvironment Shows Clinical Correlations In Ph1 Study Of Atezolizumab +/- Soc In Mm, Sandy Wong, Habib Hamidi, Luciano J Costa, Selma Bekri, Natalia Neparidze, Ravi Vij, Tina G Nielsen, Aparna Raval, Rajan Sareen, Elisabeth Wassner-Fritsch, Hearn J Cho

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel …