Supplementation with a Specific Combination of Metabolic Cofactors Ameliorates Non-Alcoholic Fatty Liver Disease and, Hepatic Fibrosis, and Insulin Resistance in Mice

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient; MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD+) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.

Lives and Deaths of Gatsby: A Semantic Reading of a Key Passage in a Powerful Text

In this article, Christine Chollier is dedicated to the question of the interpretation of a key-passage in a text. The material organization of textuality influences the response of the reader, who perceives semantic forms and makes sense of the specific combination of matter and form by actualizing semantic traits and neutralizing others, relying on contexts - internal and external - to validate or invalidate options. The piece of writing under scrutiny relates Gatsby's murder in his swimming-pool. The global context in the novel provides clues to build in and interpret local linguistic features in the light of the elegiac project.

Angiogenesis Inhibitors in Personalized Combination Regimens for the Treatment of Advanced Refractory Cancers

Background: Angiogenic factors are commonly activated in solid tumors and present a viable therapeutic target. However, anticancer treatment with angiogenesis inhibitors (AGI) is limited to a few cancers, mostly as monotherapy and not selected based on molecular indications. We aimed to determine whether patient-specific combination regimens with AGI and other anticancer agents when selected based on multi-analyte tumor interrogation (ETA: Encyclopedic Tumor Analysis) can expand the scope of AGIs in advanced refractory solid organ cancers with improved treatment responses.Methods: We evaluated treatment outcomes in 60 patients with advanced, refractory solid organ cancers who received ETA-guided combination regimens of AGI with other targeted, endocrine or cytotoxic agents. Radiological evaluation of treatment response was followed by determination of Objective Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS).Results: Among the 60 patients, Partial Response (PR) was observed in 28 cases (46.7%), Stable Disease (SD) was observed in 29 cases (48.3%) and Disease Progression (PD, within 60 days) was observed in 3 cases (5.0%). The ORR was 46.7% and DCR was 95.0%. At the most recent follow-up the median PFS (mPFS) was 5.0 months and median OS (mOS) was 8.9 months. There were no Grade 4 therapy related adverse events or treatment related deaths.Conclusion: ETA-guided patient-specific combination regimens with AGI and other anti-neoplastic agents, can yield improved outcomes over AGI monotherapy. Trial Registration: Details of all trials are available at WHO-ICTRP: https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011,808. LIQUID IMPACT ID CTRI/2019/02/017,548.

Mathematical model for the tensile strength of the crimping assembly of aviation wiring harness end

In this study, the relationship between the tensile strength and the indentation depth was studied by analysing the deformation mechanism of the crimping assembly of the aviation wiring harness end. Tensile strength tests were performed on samples of crimping assemblies with different indentation depths. The results showed that the experimental and theoretical values were in good agreement, verifying the validity of the established mathematical model for tensile strength. Based on this model, a reasonable design range for the indentation depth corresponding to the specific combination of contacts and strands was determined.

ACCURACY VALIDATION OF TILTED CAMERA SETUPS IN OPEN SKIES PROJECT AND MAPPING APPLICATIONS

Signed March 24, 1992, the Open Skies Treaty permits each state-party to conduct short-notice, unarmed, reconnaissance flights over the others' entire territories to collect data on military forces and activities. Observation aircraft equipped with sensors shall enable the observing party to identify significant military equipment. The Open Skies Treaty agreed on an observation of 30cm GSD. Based on 8 mid-format cameras for 3 flight levels, a system was adjusted to comply with the regulations. However, the overall aim was to also use the system for mapping purposes in Romania, specifically the medium altitude configuration. From this medium altitude configuration, one specific combination raised our interest. The designed wide corridor mapping system, using two RGB tilted cameras and one RGB nadir camera generates a certain range of resolution of the sideward looking tilted cameras and a non-homogenous distribution of the GSD in the overlapping areas. While a reduction of the GSD in the remote parts of the tilted cameras is a well-known and accepted fact, the effect in the overlap of the tilted cameras with the nadir one is the opposite mathematically. In some cases, such an effect can cause a better GSD in these areas than expected.

Synoptic revision of Kolobopetalum and Rhigiocarya (Menispermaceae) with the description of a new Kolobopetalum species from Gabon, and a new specific combination in Rhigiocarya from West Africa

Background and aims – In the framework of the Menispermaceae treatment for the Flore du Gabon, the closely related genera Kolobopetalum and Rhigiocarya are synoptically revised.Material and methods – Standard practices of herbarium taxonomy have been applied to study the relevant herbarium material from B, BM, BR, BRLU, HBG, K, L, P, U, and WAG. The relevant collecting data are stored in the Botany Section of the Naturalis Biodiversity Center, Leiden, The Netherlands.Key results – The distinction between the genera Kolobopetalum and Rhigiocarya is further investigated and improved. As a result, Kolobopetalum leonense is transferred to Rhigiocarya. The Gabonese collections of Kolobopetalum contained a new species named K. synsepalum, which is described and illustrated. Rhigiocarya nervosa is resurrected as a distinct species. The distribution of all species is mapped. Illustrations are provided to facilitate the use of the key for the two genera and their species.

Glioma-Specific Diffusion Signature in Diffusion Kurtosis Imaging

Purpose: This study aimed to assess the relationship between mean kurtosis (MK) and mean diffusivity (MD) values from whole-brain diffusion kurtosis imaging (DKI) parametric maps in preoperative magnetic resonance (MR) images from 2016 World Health Organization Classification of Tumors of the Central Nervous System integrated glioma groups. Methods: Seventy-seven patients with histopathologically confirmed treatment-naïve glioma were retrospectively assessed between 1 August 2013 and 30 October 2017. The area on scatter plots with a specific combination of MK and MD values, not occurring in the healthy brain, was labeled, and the corresponding voxels were visualized on the fluid-attenuated inversion recovery (FLAIR) images. Reversely, the labeled voxels were compared to those of the manually segmented tumor volume, and the Dice similarity coefficient was used to investigate their spatial overlap. Results: A specific combination of MK and MD values in whole-brain DKI maps, visualized on a two-dimensional scatter plot, exclusively occurs in glioma tissue including the perifocal infiltrative zone and is absent in tissue of the normal brain or from other intracranial compartments. Conclusions: A unique diffusion signature with a specific combination of MK and MD values from whole-brain DKI can identify diffuse glioma without any previous segmentation. This feature might influence artificial intelligence algorithms for automatic tumor segmentation and provide new aspects of tumor heterogeneity.

Tiny, ornamented eggs and eggshell from the Upper Cretaceous of Utah represent a new ootaxon with theropod affinities

A new Cretaceous ootaxon (eggshell type) from the Kaiparowits Formation of Grand Staircase-Escalante National Monument is among a growing number of very small eggs described from the Mesozoic. Analyses of two partial eggs (~ 17.7 mm in diameter) and 29 eggshell fragments reveal that this new ootaxon exhibits nodose ornamentation with distinctive branching pore canals that open atop the nodes. Its two-layered microstructure consists of a mammillary layer and a continuous layer with rugged grain boundaries between calcite grains. Although the exact identity of the egg producer is unknown, the eggshell microstructure and small size is consistent with a small-bodied avian or non-avian theropod. The specific combination of small egg size, branching pores, two-layered microstructure, and dispersituberculate ornamentation preserved in this new ootaxon is unique among theropod eggs. This underscores that both eggshell and skeletal fossils of Cretaceous theropods can display a mosaic of transitional morphological and behavioural features characteristic of both avian and non-avian taxa. As such, this new ootaxon increases the diversity of Cretaceous eggs and informs our understanding of the evolution of theropod eggshell microstructure and morphology.

Angiogenesis Inhibitors in Personalized Combination Regimens for the Treatment of Advanced Refractory Cancers

Background Angiogenic factors are commonly activated in solid tumors and present a viable therapeutic target. However, anticancer treatment with angiogenesis inhibitors (AGI) is limited to a few cancers, mostly as monotherapy and not selected based on molecular indications. We aimed to determine whether patient-specific combination regimens with AGI and other anticancer agents when selected based on multi-analyte tumor interrogation (ETA: Encyclopedic Tumor Analysis) can expand the scope of AGIs in advanced refractory solid organ cancers with improved treatment responses. Methods We evaluated treatment outcomes in 60 patients with advanced, refractory solid organ cancers who received ETA-guided combination regimens of AGI with other targeted, endocrine or cytotoxic agents. Radiological evaluation of treatment response was followed by determination of Objective Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Results Among the 60 patients, Partial Response (PR) was observed in 28 cases (46.7%), Stable Disease (SD) was observed in 29 cases (48.3%) and Disease Progression (PD, within 60 days) was observed in 3 cases (5.0%). The ORR was 46.7% and DCR was 95.0%. At the most recent follow, up the median PFS (mPFS) was 5.0 months and median OS (mOS) was 8.9 months. There were no Grade 4 therapy related adverse events or treatment related deaths. Conclusions ETA-guided patient-specific combination regimens with AGI and other anti-neoplastic agents, can yield improved outcomes over AGI monotherapy. Trial Registration Details of all trials are available at WHO-ICTRP: https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011808. LIQUID IMPACT ID CTRI/2019/02/017548.