'Gel-Stacks' gently confine or reversibly immobilize arrays of single DNA molecules for manipulation and study.

Large DNA molecules (>20 kb) are difficult analytes prone to breakage during serial manipulations and cannot be 'rescued' as full-length amplicons. Accordingly, to present, modify and analyze arrays of large, single DNA molecules, we created an easily realizable approach offering gentle confinement conditions or immobilization via spermidine condensation for controlled delivery of reagents that support live imaging by epifluorescence microscopy termed 'Gel-Stacks.' Molecules are locally confined between two hydrogel surfaces without covalent tethering to support time-lapse imaging and multistep workflows that accommodate large DNA molecules.

Smartphone and Wearable Device-Based Digital Phenotyping to Understand Substance use and its Syndemics.

Digital phenotyping is a process that allows researchers to leverage smartphone and wearable data to explore how technology use relates to behavioral health outcomes. In this Research Concepts article, we provide background on prior research that has employed digital phenotyping; the fundamentals of how digital phenotyping works, using examples from participant data; the application of digital phenotyping in the context of substance use and its syndemics; and the ethical, legal and social implications of digital phenotyping. We discuss applications for digital phenotyping in medical toxicology, as well as potential uses for digital phenotyping in future research.

Machine Learning Differentiation of Autism Spectrum Sub-Classifications.

Purpose: Disorders on the autism spectrum have characteristics that can manifest as difficulties with communication, executive functioning, daily living, and more. These challenges can be mitigated with early identification. However, diagnostic criteria has changed from DSM-IV to DSM-5, which can make diagnosing a disorder on the autism spectrum complex.

Machine learning determination of applied behavioral analysis treatment plan type.

Background: Applied behavioral analysis (ABA) is regarded as the gold standard treatment for autism spectrum disorder (ASD) and has the potential to improve outcomes for patients with ASD. It can be delivered at different intensities, which are classified as comprehensive or focused treatment approaches. Comprehensive ABA targets multiple developmental domains and involves 20-40 h/week of treatment.

Temporal and Spatiotemporal Arboviruses Forecasting by Machine Learning: A Systematic Review.

Arboviruses are a group of diseases that are transmitted by an arthropod vector. Since they are part of the Neglected Tropical Diseases that pose several public health challenges for countries around the world. The arboviruses' dynamics are governed by a combination of climatic, environmental, and human mobility factors.

Amplification of the CXCR3/CXCL9 axis via intratumoral electroporation of plasmid CXCL9 synergizes with plasmid IL-12 therapy to elicit robust anti-tumor immunity.

Clinical studies have demonstrated that local expression of the cytokine IL-12 drives interferon-gamma expression and recruits T cells to the tumor microenvironment, ultimately yielding durable systemic T cell responses. Interrogation of longitudinal biomarker data from our late-stage melanoma trials identified a significant on-treatment increase of intratumoral transcripts that was restricted to responding patients, underscoring the clinical relevance of tumor-infiltrating CXCR3 immune cells. In this study, we sought to understand if the addition of DNA-encodable CXCL9 could augment the anti-tumor immune responses driven by intratumoral IL-12.

Intratumoral Electroporation of Plasmid Encoded IL12 and Membrane-Anchored Anti-CD3 Increases Systemic Tumor Immunity.

Unlabelled: Intratumoral delivery of plasmid IL12 via electroporation (IT-tavo-EP) induces localized expression of IL12 leading to regression of treated and distant tumors with durable responses and minimal toxicity. A key driver in amplifying this local therapy into a systemic response is the magnitude and composition of immune infiltrate in the treated tumor. While intratumoral IL12 typically increases the density of CD3+ tumor-infiltrating lymphocytes (TIL), this infiltrate is composed of a broad range of T-cell subsets, including activated tumor-specific T cells, less functional bystander T cells, as well as suppressive T regulatory cells.

A First Report of HCTZ and Dicyclomine Induced Uncharacteristic Contraction Alkalosis.

Contraction alkalosis is characterized by low serum sodium and chloride and high serum carbon dioxide and bicarbonate levels. A 28-year-old Caucasian active-duty male with a history of autosomal dominant polycystic kidney disease and diarrhea-predominant Irritable Bowel Syndrome (D-IBS) presented to his primary care provider (PCP) with elevated blood pressure (136/96 mmHg), was diagnosed with stage-2 hypertension, and started oral HCTZ (25 mg/day). His medications included dicyclomine (10 mg oral three times daily).

Androgen Receptor-Mediated Nuclear Transport of NRDP1 in Prostate Cancer Cells Is Associated with Worse Patient Outcomes.

To our knowledge, our group is the first to demonstrate that NRDP1 is located in the nucleus as well as the cytoplasm of CaP cells. Subcellular fractionation, immunohistochemistry, and immunofluorescence analysis combined with confocal microscopy were used to validate this finding. Subcellular fractionation followed by western blot analysis revealed a strong association between AR and NRDP1 localization when AR expression and/or cellular localization was manipulated via treatment with R1881, AR-specific siRNA, or enzalutamide.

Occurrence of Lead and Other Toxic Metals Derived from Drinking-Water Systems in Three West African Countries.

Background: Exposure to toxic metals (TMs) such as lead can cause lifelong neurodevelopmental impairment and other adverse outcomes. TMs enter drinking water from human activity, geogenic contamination, and corrosion of water system components. Several studies report TM contamination in piped systems and private wells in high-income countries (HICs).

Intratumoral Plasmid IL12 Expands CD8 T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti-PD-1 Therapy.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.

Awareness and use of telephone-based behaviour change support services among clients of a community mental health service.

Objective: To determine the prevalence of, and factors associated with, awareness and use of telephone-based behaviour change support services among clients of a community mental health service.

Methods: Adult clients (n=375) of one Australian community mental health service completed a telephone interview and self-reported not meeting Australian National Guidelines for smoking, nutrition, alcohol consumption and/or physical activity. Descriptive statistics summarised awareness and use of the New South Wales Quitline and Get Healthy Service for participants with lifestyle risk factors addressed by each service.

Treatment With Gemfibrozil Prevents the Progression of Chronic Kidney Disease in Obese Dahl Salt-Sensitive Rats.

Recently, we reported that Dahl salt-sensitive leptin receptor mutant (SSmutant) rats exhibit dyslipidemia and renal lipid accumulation independent of hyperglycemia that progresses to chronic kidney disease (CKD). Therefore, in the current study, we examined the effects of gemfibrozil, a lipid-lowering drug (200 mg/kg/day, orally), on the progression of renal injury in SS and SSmutant rats for 4 weeks starting at 12 weeks of age. Plasma triglyceride levels were markedly elevated in the SSmutant strain compared to SS rats (1193 ± 243 and 98 ± 16 mg/day, respectively).

Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

Purpose: Tumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).

Patients And Methods: Tavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.

Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients.

Background: Interleukin 12 (IL-12) is a pivotal regulator of innate and adaptive immunity. We conducted a prospective open-label, phase II clinical trial of electroporated plasmid IL-12 in advanced melanoma patients (NCT01502293).

Patients And Methods: Patients with stage III/IV melanoma were treated intratumorally with plasmid encoding IL-12 (tavokinogene telseplasmid; tavo), 0.

Data Integration for Large-Scale Models of Species Distributions.

With the expansion in the quantity and types of biodiversity data being collected, there is a need to find ways to combine these different sources to provide cohesive summaries of species' potential and realized distributions in space and time. Recently, model-based data integration has emerged as a means to achieve this by combining datasets in ways that retain the strengths of each. We describe a flexible approach to data integration using point process models, which provide a convenient way to translate across ecological currencies.

Imaging of cancer lipid metabolism in response to therapy.

Lipids represent a diverse array of molecules essential to the cell's structure, defense, energy, and communication. Lipid metabolism can often become dysregulated during tumor development. During cancer therapy, targeted inhibition of cell proliferation can likewise cause widespread and drastic changes in lipid composition.

Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12.

Anti-PD-1 immune checkpoint blockers can induce sustained clinical responses in cancer but how they function in vivo remains incompletely understood. Here, we combined intravital real-time imaging with single-cell RNA sequencing analysis and mouse models to uncover anti-PD-1 pharmacodynamics directly within tumors. We showed that effective antitumor responses required a subset of tumor-infiltrating dendritic cells (DCs), which produced interleukin 12 (IL-12).

Altered states of consciousness among inpatients in a Trauma Program.

A set of measures of trauma, dissociation, altered states of consciousness, and spiritual experiences was administered to a convenience sample of 100 inpatients in a hospital Trauma Program. The inpatients had an average Dissociative Experiences Scale score of 42.3 and an average Adverse Childhood Experiences Scale score of 6.

Bat detective-Deep learning tools for bat acoustic signal detection.

Passive acoustic sensing has emerged as a powerful tool for quantifying anthropogenic impacts on biodiversity, especially for echolocating bat species. To better assess bat population trends there is a critical need for accurate, reliable, and open source tools that allow the detection and classification of bat calls in large collections of audio recordings. The majority of existing tools are commercial or have focused on the species classification task, neglecting the important problem of first localizing echolocation calls in audio which is particularly problematic in noisy recordings.

Reflective Debriefing: A Social Work Intervention Addressing Moral Distress among ICU Nurses.

Health-care workers may experience moral distress when they are unable to act as they believe is ethically appropriate in their clinical work. A social worker-facilitated protocol called Reflective Debriefing was developed and tested for alleviating moral distress through regular debriefings with nursing staff on an intensive care unit (ICU). Forty-two ICU nurses completed a Moral Distress Scale-Revised (MDS-R) at the beginning and end of a 6-month period, during which time regular debriefings were offered.

Improving the efficacy and safety of biologic drugs with tolerogenic nanoparticles.

The development of antidrug antibodies (ADAs) is a common cause for the failure of biotherapeutic treatments and adverse hypersensitivity reactions. Here we demonstrate that poly(lactic-co-glycolic acid) (PLGA) nanoparticles carrying rapamycin, but not free rapamycin, are capable of inducing durable immunological tolerance to co-administered proteins that is characterized by the induction of tolerogenic dendritic cells, an increase in regulatory T cells, a reduction in B cell activation and germinal centre formation, and the inhibition of antigen-specific hypersensitivity reactions. Intravenous co-administration of tolerogenic nanoparticles with pegylated uricase inhibited the formation of ADAs in mice and non-human primates and normalized serum uric acid levels in uricase-deficient mice.

The self-report Dissociative Disorders Interview Schedule: A preliminary report.

A self-report version of the Dissociative Disorders Interview Schedule (SR-DDIS) was administered to 100 inpatients in a hospital-based trauma program. All participants had previously completed the interviewer-administered version of the DDIS. When we compared the overall results on the DDIS and SR-DDIS for the 100 inpatients, the findings were very consistent for both symptom clusters and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), diagnoses.