Argument-based inductive logics, with coverage of compromised perception.

Formal deductive logic, used to express and reason over declarative, axiomatizable content, captures, we now know, essentially all of what is known in mathematics and physics, and captures as well the details of the proofs by which such knowledge has been secured. This is certainly impressive, but deductive logic alone cannot enable rational adjudication of arguments that are at variance (however much additional information is added). After affirming a fundamental directive, according to which argumentation should be the basis for human-centric AI, we introduce and employ both a deductive and-crucially-an inductive cognitive calculus. The former cognitive calculus, DCEC, is the deductive one and is used with our automated deductive reasoner ShadowProver; the latter, IDCEC, is inductive, is used with the automated inductive reasoner ShadowAdjudicator, and is based on human-used concepts of likelihood (and in some dialects of IDCEC, probability). We explain that ShadowAdjudicator centers around the concept of competing and nuanced arguments adjudicated non-monotonically through time. We make things clearer and more concrete by way of three case studies, in which our two automated reasoners are employed. Case Study 1 involves the famous Monty Hall Problem. Case Study 2 makes vivid the efficacy of our calculi and automated reasoners in simulations that involve a cognitive robot (PERI.2). In Case Study 3, as we explain, the simulation employs the cognitive architecture ARCADIA, which is designed to computationally model human-level cognition in ways that take perception and attention seriously. We also discuss a type of argument rarely analyzed in logic-based AI; arguments intended to persuade by leveraging human deficiencies. We end by sharing thoughts about the future of research and associated engineering of the type that we have displayed.

Drug Delivery Systems Using Surface Markers for Targeting Cancer Stem Cells.

The innate abilities of cancer stem cells (CSCs), such as multi-drug resistance, drug efflux, quiescence and ionizing radiation tolerance, protect them from most traditional chemotherapeutics. As a result, this small subpopulation of persistent cells leads to more aggressive and chemoresistant cancers, causing tumour relapse and metastasis. This subpopulation is differentiated from the bulk tumour population through a wide variety of surface markers expressed on the cell surface. Recent developments in nanomedicine and targeting delivery methods have given rise to new possibilities for specifically targeting these markers and preferentially eliminating CSCs. Herein, we first summarize the range of surface markers identifying CSC populations in a variety of cancers; then, we discuss recent attempts to actively target CSCs and their niches using liposomal, nanoparticle, carbon nanotube and viral formulations.

Use of Anticancer Platinum Compounds in Combination Therapies and Challenges in Drug Delivery.

As one of the leading and most important metal-based drugs, platinum-based pharmaceuticals are widely used in the treatment of solid malignancies. Despite significant side effects and acquired drug resistance have limited their clinical applications, platinum has shown strong inhibitory effects for a wide assortment of tumors. Drug delivery systems using emerging technologies such as liposomes, dendrimers, polymers, nanotubes and other nanocompositions, all show promise for the safe delivery of platinum-based compounds. Due to the specificity of nano-formulations; unwanted side-effects and drug resistance can be largely averted. In addition, combinational therapy has been shown to be an effective way to improve the efficacy of platinum based anti-tumor drugs. This review first introduces drug delivery systems used for platinum and combinational therapeutic delivery. Then we highlight some of the recent advances in the field of drug delivery for combinational therapy; specifically progress in leveraging the cytotoxic nature of platinum-based drugs, the combinational effect of other drugs with platinum, while evaluating the drug targeting, side effect reducing and sitespecific nature of nanotechnology-based delivery platforms.

Biomimetic Octopus-like Particles for Ultraspecific Capture and Detection of Pathogens.

Infectious diseases caused by pathogenic bacteria (such as sepsis and meningitis) seriously threaten public health; therefore, rapid and accurate identification of the target bacteria is urgently needed to prevent and treat bacterial infections. Although technologies including plate-counting and polymerase chain reaction have been established to detect the pathogenic bacteria, they are either time-consuming or sophisticated. Herein, a biomimetic octopus-like structure integrating merits of multiarm and multivalent interaction is designed for ultraspecific capture and detection of pathogens. The flexible polymeric arms and multivalent ligands work together to mimic the arm-sucker coordination of an octopus to effectively grasp the target pathogens, leading to remarkably high capacity and specificity for the target capture (above 98%, 10 CFU mL-1) without a nonspecific absorption of background pathogens. The captured bacteria can be identified as a point of care by the surface-enhanced Raman spectroscopy method with a detection limit of 10 cells mL-1.

TPGS modified nanoliposomes as an effective ocular delivery system to treat glaucoma.

The aim of this study is to investigate the potential of D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) modified nanoliposomes as an ophthalmic delivery system of brinzolamide (Brz) for glaucoma treatment. The Brz loaded nanoliposomes containing TPGS (T-LPs/Brz) were firstly developed by a thin-film dispersion method. The average particle size was 96.87 ±â€¯4.43 nm. The entrapment efficiency of the Brz was 95.41 ±â€¯3.03% and the drug loading was 4.00 ±â€¯0.13%. T-LPs/Brz exhibited obvious sustained release of Brz; in stark contrast to the normal liposomes of Brz (LPs/Brz) and the commercial formulation AZOPT® (Brz ophthalmic suspension, Brz-Sus). Enhanced trans-corneal transport of Brz was achieved with T-LPs/Brz. Compared with both Brz-Sus and LPs/Brz, the apparent permeability coefficient (Papp) of T-LPs/Brz was 10.2 folds and 1.38 folds higher, respectively. Moreover, T-LPs/Brz extended the cornea residence of Brz. White New Zealand rabbits treated with T-LPs/Brz had 3.18 folds and 1.57 folds Brz concentration 2 h after treatment than Brz-Sus and LPs/Brz, respectively. Further pharmacodynamic studies showed that T-LPs/Brz maintained an effective intraocular pressure (IOP) reduction from 3 h to 11 h after administration, while Brz-Sus and LPs/Brz presented effective IOP decreases from 3 h to 6 h and 3 h to 8 h respectively. The preliminary safety evaluation demonstrated that T-LPs/Brz had no significant side effects; specifically, no cornea damage and eye irritation. All the results indicated that TPGS modified nanoliposomes were a promising ocular delivery carriers for Brz to treat glaucoma. As such, T-LPs/Brz might be worthy of further translational study.

Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA.

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a well-characterized tumour-suppressor gene that is lost or mutated in about half of metastatic castration-resistant prostate cancers and in many other human cancers. The restoration of functional PTEN as a treatment for prostate cancer has, however, proven difficult. Here, we show that PTEN messenger RNA (mRNA) can be reintroduced into PTEN-null prostate cancer cells in vitro and in vivo via its encapsulation in polymer-lipid hybrid nanoparticles coated with a polyethylene glycol shell. The nanoparticles are stable in serum, elicit low toxicity and enable high PTEN mRNA transfection in prostate cancer cells. Moreover, significant inhibition of tumour growth is achieved when delivered systemically in multiple mouse models of prostate cancer. We also show that the restoration of PTEN function in PTEN-null prostate cancer cells inhibits the phosphatidylinositol 3-kinase (PI3K)-AKT pathway and enhances apoptosis. Our findings provide proof-of-principle evidence of the restoration of mRNA-based tumour suppression in vivo.

Author Correction: Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA.

The authors wish to add the following sentence into the 'Competing interests' section of this Article: "P.W.K. has investment interest in Context Therapeutics LLC, DRGT, Placon, Seer Biosciences and Tarveda Therapeutics, is a company board member for Context Therapeutics LLC, is a consultant and scientific advisory board member for BIND Biosciences, Inc., BN Immunotherapeutics, DRGT, GE Healthcare, Janssen, Metamark, New England Research Institutes, Inc., OncoCellMDX, Progenity, Sanofi, Seer Biosciences, Tarveda Therapeutics and Thermo Fisher, and serves on data safety monitoring boards for Genentech/Roche and Merck." This has now been included.

Early Secondary Neurologic Deterioration After Blunt Spinal Trauma: A Review of the Literature.

OBJECTIVES: The objectives were to review published reports of secondary neurologic deterioration in the early stages of care after blunt spinal trauma and describe its nature, context, and associated risk factors. METHODS: The authors searched the MEDLINE, EMBASE, and CINAHL databases for English-language studies. Cases were included meeting the criteria age 16 years or older, nonpenetrating trauma, and experiencing neurologic deterioration during prehospital or emergency department (ED) care prior to definitive management (e.g., discharge, spinal clearance by computed tomography, admission to an inpatient service, or surgical intervention). Results were qualitatively analyzed for characteristics and themes. RESULTS: Forty-one qualifying cases were identified from 12 papers. In 30 cases, the new deficits were apparently spontaneous and were not detected until routine reassessment. In 12 cases the authors did attribute deterioration to temporally associated precipitants, seven of which were possibly iatrogenic; these included removal of a cervical collar, placement of a halo device, patient agitation, performance of flexion/extension films, "unintentional manipulation," falling in or near the ED, and forced collar application in patients with ankylosing spondylitis. Thirteen cases occurred during prehospital care, none of them sudden and movement-provoked, and all reported by a single study. CONCLUSIONS: Published reports of early secondary neurologic deterioration after blunt spinal trauma are exceptionally rare and generally poorly documented. High-risk features may include altered mental status and ankylosing spondylitis. It is unclear how often events are linked with spontaneous patient movement and whether such events are preventable.