The vaccinia virus based Sementis Copenhagen Vector vaccine against Zika and chikungunya is immunogenic in non-human primates.

The Sementis Copenhagen Vector (SCV) is a new vaccinia virus-derived, multiplication-defective, vaccine technology assessed herein in non-human primates. Indian rhesus macaques () were vaccinated with a multi-pathogen recombinant SCV vaccine encoding the structural polyproteins of both Zika virus (ZIKV) and chikungunya virus (CHIKV). After one vaccination, neutralising antibody responses to ZIKV and four strains of CHIKV, representative of distinct viral genotypes, were generated.

Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality.

Background: DNA methylation patterns associated with habitual diet have not been well studied.

Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants.

Validation and Disease Risk Assessment of Previously Reported Genome-Wide Genetic Variants Associated With Brugada Syndrome: SADS-TW BrS Registry.

Background: Brugada syndrome (BrS) is an oligogenic arrhythmic disease with increased risk of sudden cardiac arrest. Several BrS or ECG traits-related single-nucleotide polymorphisms (SNPs) were identified through previous genome-wide association studies in white patients. We aimed to validate these SNPs in BrS patients in the Taiwanese population, assessing the cumulative effect of risk alleles and the BrS-polygenic risk score in predicting cardiac events.

Characterization of the Hydrolysis Kinetics of Fucosylated Glycosaminoglycan in Mild Acid and Structures of the Resulting Oligosaccharides.

Mild acid hydrolysis is a common method for the structure analysis of fucosylated glycosaminoglycan (FG). In this work, the effects of acid hydrolysis on the structure of FG from S. variegatus (SvFG) and the reaction characteristic were systemically studied.

Acid-labile anhydride-linked doxorubicin-doxorubicin dimer nanoparticles as drug self-delivery system with minimized premature drug leakage and enhanced anti-tumor efficacy.

Acid-labile anhydride-linked doxorubicin-doxorubicin dimers (D-DOX) were designed as doxorubicin-doxorubicin conjugate-based drug self-delivery systems (DSDSs) with high drug content for tumor intracellular pH-triggered release, by conjugating doxorubicin (DOX) with various anhydrides, such as maleic anhydride (MAH), succinic anhydride (suc), and 2,3-dimethylmaleic anhydride (DMMAH). With the similar diameter of about 200 nm, the D-DOX showed better pH-triggered DOX release and was thus selected for the further investigation. The D-DOX-5 nanoparticles with desirable average hydrodynamic diameter (D) of 162 nm and high drug content of 51.

Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models.

Chikungunya virus (CHIKV), Ross River virus (RRV), o'nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex.

Toxicity, migration and transformation characteristics of lead in soil-plant system: Effect of lead species.

Lead (Pb) is a typical hazardous element of high concern in species characteristics involving toxicity, migration and transformation. A greenhouse experiment was conducted using Solanum nigrum L. grown in soils treated by divalent (Pb), tetravalent (Pb), trimethyl (TML) and triethyl (TEL) lead for 60 days.

Cyclophane-Sustained Ultrastable Porphyrins.

We report the encapsulation of free-base and zinc porphyrins by a tricyclic cyclophane receptor with subnanomolar binding affinities in water. The high affinities are sustained by the hydrophobic effect and multiple [CH···π] interactions covering large [π···π] stacking surfaces between the substrate porphyrins and the receptor. We discovered two co-conformational isomers of the 1:1 complex, where the porphyrin is orientated differently inside the binding cavity of the receptor on account of its tricyclic nature.

Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites.

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence.

Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor.

Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. ).

Small-sized gadolinium oxide based nanoparticles for high-efficiency theranostics of orthotopic glioblastoma.

Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size.

Chronic Non-Malignant Pain in Patients with Cancer Seen at a Timely Outpatient Palliative Care Clinic.

Palliative care is seeing cancer patients earlier in the disease trajectory with a multitude of chronic issues. Chronic non-malignant pain (CNMP) in cancer patients is under-studied. In this prospective study, we examined the prevalence and management of CNMP in cancer patients seen at our supportive care clinic for consultation.

Combined toxicity and detoxification of lead, cadmium and arsenic in Solanum nigrum L.

A 3-factor-5-level central composite design was conducted to investigate the combined toxicity and detoxification mechanisms of lead (Pb), cadmium (Cd) and arsenic (As) in Solanum nigrum L. The three metal(loid)s exhibited low-dose stimulation and high-dose inhibition on plant length. Analyses of eleven oxidative stress and antioxidant parameters showed all Pb, Cd and As induced oxidative damages, and the co-exposure further enhanced their toxic effects.

Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia.

Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (IDH1; mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received 500 mg ivosidenib daily. Median age was 76.

Effects of Co(II) ion exchange, Ni(II)- and V(V)-doping on the transformation behaviors of Cr(III) on hexagonal turbostratic birnessite-water interfaces.

Natural birnessite-like minerals are commonly enriched in various transitional metals (TMs), which greatly modify the mineral structure and properties. However few studies are yet conducted systematically on the effects of TM doping on birnessite reactivity towards Cr(III) oxidation. In the present study, the transformation behaviors of Cr(III) on Co-, Ni-, V-containing birnessites were investigated.

Epigynumgenane-type pregnane glycosides from Epigynum cochinchinensis and their immunosuppressive activity.

Five undescribed C pregnane glycosides, epigycosides D-H, together with four known analogues, two lignans, and a flavonoid have been isolated from the stems of Epigynum cochinchinensis. The structures of pregnane glycosides were elucidated using spectroscopic techniques and acid hydrolysis. The in vitro immunological activities were assessed against Con A-stimulated proliferation of mice splenocytes.

Core-shell-corona chitosan-based micelles for tumor intracellular pH-triggered drug delivery: Improving performance by grafting polycation.

Core-shell-corona chitosan-based micelles were designed for the tumor intracellular pH-triggered doxorubicin (DOX) delivery, via a facile in-situ micellization in an aqueous solution of DOX and polyethylene glycol (PEG) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) dual-modified chitosan (PEG-g-CS-g-PDPA). The effect of the PDPA modification on the diameter, drug loading-capacity (DLC) and pH-triggered drug release was investigated for the three different polymerization degrees of PDPA (25, 32, and 42) with a similar modification degree of ~22%. The optimized ones, the core-shell-corona DOX/PEG-g-CS-g-PDPA micelles possessed a mean hydrodynamic diameter (D) of 211 nm and DLC of 54%, showing an excellent pH-triggered drug release with negligible premature drug leakage in 60 h.

Genetic risk of Parkinson disease and progression:: An analysis of 13 longitudinal cohorts.

Objective: To determine if any association between previously identified alleles that confer risk for Parkinson disease and variables measuring disease progression.

Methods: We evaluated the association between 31 risk variants and variables measuring disease progression. A total of 23,423 visits by 4,307 patients of European ancestry from 13 longitudinal cohorts in Europe, North America, and Australia were analyzed.

Predicting 10-Year and Lifetime Stroke Risk in Chinese Population.

Background and Purpose- Risk assessment is essential for the primary prevention of stroke. However, the current available tools derived from Chinese populations are insufficient for individualized 10-year and lifetime stroke risk prediction. Our study aims to develop and validate personalized 10-year and lifetime stroke risk equations incorporating 4 large Chinese cohorts.

Maternal Cardiovascular Dysregulation During Early Pregnancy After In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.

Commonly used in vitro fertilization protocols produce pregnancies without a corpus luteum (CL), a major source of reproductive hormones. In vitro fertilization pregnancies without a CL showed deficient gestational increases of central (aortic) arterial compliance during the first trimester and were at increased risk for developing preeclampsia. Here, we investigated whether there was generalized impairment of cardiovascular adaptation in in vitro fertilization pregnancies without a CL compared with pregnancies conceived spontaneously or through ovarian stimulation, which lead to 1 and >1 CL, respectively (n=19-26 participants per cohort).

Similar image search for histopathology: SMILY.

The increasing availability of large institutional and public histopathology image datasets is enabling the searching of these datasets for diagnosis, research, and education. Although these datasets typically have associated metadata such as diagnosis or clinical notes, even carefully curated datasets rarely contain annotations of the location of regions of interest on each image. As pathology images are extremely large (up to 100,000 pixels in each dimension), further laborious visual search of each image may be needed to find the feature of interest.

Development and validation of a deep learning algorithm for improving Gleason scoring of prostate cancer.

For prostate cancer patients, the Gleason score is one of the most important prognostic factors, potentially determining treatment independent of the stage. However, Gleason scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility. Here we present a deep learning system (DLS) for Gleason scoring whole-slide images of prostatectomies.

Superior Trunk Block: A Phrenic-sparing Alternative to the Interscalene Block: A Randomized Controlled Trial.

Background: Interscalene nerve blockade remains one of the most commonly used anesthetic and analgesic approaches for shoulder surgery. The high incidence of hemidiaphragmatic paralysis associated with the block, however, precludes its use among patients with compromised pulmonary function. To address this issue, recent studies have investigated phrenic-sparing alternatives that provide analgesia.

Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration.

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole.