Poly(d,l-lactide-co-glycolide) Nanoparticles as Delivery Platforms for TLR7/8 Agonist-Based Cancer Vaccine.

Targeted drug delivery can significantly influence the efficacy of a drug. In the past decades, diverse drug-delivery technologies, including nano- and microparticles, co-crystals, and microneedles have been developed to maximize therapeutic efficacy and minimize undesired side effects of therapeutics. Nanoparticles-submicron-sized drug carriers-have been actively investigated for the delivery of antibiotics, nucleic acids, peptide/proteins, and chemotherapeutics.

Characterization of solvent-fractionated lignins from woody biomass treated via supercritical water oxidation.

Crude supercritical lignin (SCL) extracted from hardwood (Quercus mongolica) treated via supercritical water (SCW) oxidation was subjected to sequential fractionation with four organic solvents; five lignin fractions (F1-F4 and F) were thus obtained. The molecular weight (MW) of the fractionated lignins gradually increased as fractionation proceeded. However, the content of methoxyl groups and phenolic hydroxyl groups tended to decrease with increasing molecular weight of the lignins.

Thoracic endovascular repair technique for the treatment of patent ductus arteriosus in an elderly patient: A case report.

Rationale: Patent ductus arteriosus (PDA) ligation by open surgery is more difficult and dangerous in elderly patients than in infants. Nowadays, simple and safe interventional catheterization technology is used for the closure of uncomplicated isolated PDAs. Therefore, an alternative less invasive therapeutic option must be developed to treat complicated PDA.

Cytomegalovirus Infection in Allogeneic Hematopoietic Cell Transplantation Managed by the Preemptive Approach: Estimating the Impact on Healthcare Resource Utilization and Outcomes.

We quantified cytomegalovirus (CMV) antiviral use and hospital length of stay (LOS) associated with CMV infection in a contemporary cohort of conventional (CONV) and CD34-selected (T cell-depleted) hematopoietic cell transplantation (HCT) recipients managed by preemptive therapy (PET) in a single US center. Adults who received first allogeneic HCT at Memorial Sloan Kettering Cancer Center from June 2010 through December 2014 were analyzed. Days on PET, number of readmissions, and readmission LOS by day 180 post-HCT were summarized.

Extracellular polymeric substance (EPS)-degrading enzymes reduce staphylococcal surface attachment and biocide resistance on pig skin in vivo.

Staphylococcal extracellular polymeric substances (EPS) such as extracellular DNA (eDNA) and poly-N-acetylglucosamine surface polysaccharide (PNAG) mediate numerous virulence traits including host colonization and antimicrobial resistance. Previous studies showed that EPS-degrading enzymes increase staphylococcal biocide susceptibility in vitro and in vivo, and decrease virulence in animal models. In the present study we tested the effect of EPS-degrading enzymes on staphylococcal skin colonization and povidone iodine susceptibility using a novel in vivo pig model that enabled us to colonize and treat 96 isolated areas of skin on a single animal in vivo.

Overcoming Drug Resistance by Targeting Cancer Bioenergetics with an Activatable Prodrug.

Nearly without exception, all known cancer chemotherapeutics elicit a resistance response over time. The resulting resistance is correlated with poor clinical outcomes. Here, we report an approach to overcoming resistance through reprogramming oncogene-directed alterations in mitochondrial metabolism before drug activation while simultaneously circumventing drug efflux pumps.

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.

Methods: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily.

Radiomic MRI Phenotyping of Glioblastoma: Improving Survival Prediction.

Purpose To investigate whether radiomic features at MRI improve survival prediction in patients with glioblastoma multiforme (GBM) when they are integrated with clinical and genetic profiles. Materials and Methods Data in patients with a diagnosis of GBM between December 2009 and January 2017 (217 patients) were retrospectively reviewed up to May 2017 and allocated to training and test sets (3:1 ratio). Radiomic features (n = 796) were extracted from multiparametric MRI.

Dichomitus squalens partially tailors its molecular responses to the composition of solid wood.

White-rot fungi, such as Dichomitus squalens, degrade all wood components and inhabit mixed-wood forests containing both soft- and hardwood species. In this study, we evaluated how D. squalens responded to the compositional differences in softwood [guaiacyl (G) lignin and higher mannan content] and hardwood [syringyl/guaiacyl (S/G) lignin and higher xylan content] using semi-natural solid cultures.

TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants.

Purpose: TANGO2-related disorders were first described in 2016 and prior to this publication, only 15 individuals with TANGO2-related disorder were described in the literature. Primary features include metabolic crisis with rhabdomyolysis, encephalopathy, intellectual disability, seizures, and cardiac arrhythmias. We assess whether genotype and phenotype of TANGO2-related disorder has expanded since the initial discovery and determine the efficacy of exome sequencing (ES) as a diagnostic tool for detecting variants.

Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer.

While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression.

Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease.

Objective: To investigate the effects of completed pregnancy with childbirth and incomplete pregnancy without childbirth on the late-life cognition and the risk of Alzheimer disease (AD) in women.

Methods: Using the pooled data of 3,549 women provided by 2 population-based cohort studies, we conducted logistic regression analyses to examine retrospectively the associations of completed and incomplete pregnancy with the risks of mild cognitive impairment and AD. For women without dementia, we also conducted analyses of covariance to examine the associations of completed and incomplete pregnancy with Mini-Mental State Examination (MMSE) score.

Benefit of Prolonged Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stent for Coronary Bifurcation Lesions: Results From the Coronary Bifurcation Stenting Registry II.

Background: Whether prolonged dual antiplatelet therapy (DAPT) improves clinical outcomes after percutaneous coronary intervention for coronary bifurcation lesion is uncertain.

Methods And Results: We evaluated 2082 patients who were treated with drug-eluting stent for bifurcation lesions and were event free (no death, myocardial infarction [MI], cerebrovascular accident, stent thrombosis, or any revascularization) at 12 months after the index procedure. Patients were divided into 2 groups: DAPT ≥12-month group (n=1776) and DAPT <12-month group (n=306).

Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis.

Background: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.

Methods: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks.

Structural Characterization of Lignins from Willow Bark and Wood.

Understanding the chemical structure of lignin in willow bark is an indispensable step to design how to separate its fiber bundles. The whole cell wall and enzyme lignin preparations sequentially isolated from ball-milled bark, inner bark, and wood were comparatively investigated by nuclear magnetic resonance (NMR) spectroscopy and three classical degradative methods, i.e.

Electrocardiograms in Healthy North American Children in the Digital Age.

Background: Interpretation of pediatric ECGs is limited by lack of accurate sex- and race-specific normal reference values obtained with modern technology for all ages. We sought to obtain contemporary digital ECG measurements in healthy children from North America, to evaluate the effects of sex and race, and to compare our results to commonly used published datasets.

Methods: Digital ECGs (12-lead) were retrospectively collected for children ≤18 years old with normal echocardiograms at 19 centers in the Pediatric Heart Network.

Time to stroke: A Western Trauma Association multicenter study of blunt cerebrovascular injuries.

Background: Screening for blunt cerebrovascular injuries (BCVIs) in asymptomatic high-risk patients has become routine. To date, the length of this asymptomatic period has not been defined. Determining the time to stroke could impact therapy including earlier initiation of antithrombotics in multiply injured patients.

Association Between Prescription Drug Monitoring Programs and Nonfatal and Fatal Drug Overdoses: A Systematic Review.

Background: Prescription drug monitoring programs (PDMPs) are a key component of the president's Prescription Drug Abuse Prevention Plan to prevent opioid overdoses in the United States.

Purpose: To examine whether PDMP implementation is associated with changes in nonfatal and fatal overdoses; identify features of programs differentially associated with those outcomes; and investigate any potential unintended consequences of the programs.

Data Sources: Eligible publications from MEDLINE, Current Contents Connect (Clarivate Analytics), Science Citation Index (Clarivate Analytics), Social Sciences Citation Index (Clarivate Analytics), and ProQuest Dissertations indexed through 27 December 2017 and additional studies from reference lists.

Can Shoulder Muscle Activity Be Evaluated With Ultrasound Shear Wave Elastography?

Background: Quantitative assessment of rotator cuff muscle activity is important in the treatment of shoulder disorders. However, the known methods for assessing rotator cuff muscle activity thus far have been inaccurate, invasive, and inconvenient.

Questions/purposes: (1) Does the activity of the deltoid, supraspinatus, and infraspinatus muscles measured using ultrasound shear wave elastography have a linear correlation with muscle activity assessed using generally used methods, including isokinetic dynamometry and electromyography? (2) Does the activity of the deltoid, supraspinatus, and infraspinatus muscles measured using shear wave elastography show good intraobserver and interobserver reliability?

Methods: Twelve volunteers participated in intrasession reliability experiments.

Intraprocedural Ablation Margin Assessment by Using Ammonia Perfusion PET during FDG PET/CT-guided Liver Tumor Ablation: A Pilot Study.

Purpose To prospectively determine whether nitrogen 13 (N) ammonia perfusion positron emission tomography (PET) during fluorine 18 fluorodeoxyglucose (FDG) PET/computed tomography (CT)-guided liver tumor ablation can be used to intraprocedurally assess ablation margins. Materials and Methods Eight patients (five women and three men; age range, 36-74 years; mean age, 57 years) were enrolled in this pilot study and underwent FDG PET/CT-guided microwave ablation of 11 FDG-avid liver metastases (mean diameter, 22 mm; range, 11-34 mm). All procedures were performed between March 2014 and December 2016.

Whole-Tumor Histogram and Texture Analyses of DTI for Evaluation of -Mutation and 1p/19q-Codeletion Status in World Health Organization Grade II Gliomas.

Background And Purpose: Prediction of the (IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine -mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.

Materials And Methods: Ninety-three patients with World Health Organization grade II gliomas with known mutation and 1p/19q-codeletion status (18 wild-type, 45 mutant and no 1p/19q codeletion, 30 mutant and 1p/19q codeleted tumors) underwent DTI.

Crystal structure of d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase from Yersinia pseudotuberculosis.

The Gram-negative bacterium Yersinia pseudotuberculosis is the causative agent of yersiniosis. d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC) is the fourth enzyme of the GDP-d-glycero-α-d-manno-heptose biosynthesis pathway which is important for the virulence of the microorganism. Therefore, HddC is a potential target of antibiotics against yersiniosis.

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids.

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS).

Low Graft Attenuation at Unenhanced CT: Association with 1-Month Mortality or Graft Failure after Liver Transplantation.

Purpose To investigate whether low graft attenuation at unenhanced computed tomography (CT) is associated with 1-month mortality or graft failure after liver transplant and determine its diagnostic performance. Materials and Methods Included were 663 recipients who underwent CT imaging within 7 days after liver transplant between December 2014 and August 2016. Initial poor function (IPF) was diagnosed by using a combination of laboratory values within 7 days after liver transplant and subdivided patients into primary and secondary IPF.