bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chlorinated Natural Products and Related Halogenases
Authors: Zeng Jia , Zhan Jixun 
Published: March 2019

AbstractHalogenated compounds are well‐known for their diverse bioactivities and wide applications in pharmaceutical industry, chemical engineering and other fields. Novel halometabolites isolated from nature inspire scientists to synthesize these “chance compounds”, which were, however, usually hampered by the extreme catalytic conditions and severe selectivity challenges. In the past several decades, enzymatic reactions have been brought into attention for their efficiency, selectivity, and mild reaction conditions. Synthetic biology which is in compliance with the laws of nature to a large extent shed light on the rational biosynthesis of halogenated compounds. This article summarizes several representative categories of halogenated natural products and halogenases to seek clues to the relationship between the structures and halogenase mechanisms. Some types of halogenase convert the basic building blocks to diverse early intermediates during natural product biosynthetic processes, while others are involved in the late tailoring steps to afford the final structures of halogenated molecules. The broad substrate specificity and strong regioselectivity exhibited in some halogenases are irreplaceable advantages for biosynthesis. In addition, tremendous efforts and encouraging results enable us to engineer the enzymes or techniques to synthesize “unnatural” halogenated natural products. More reaction mechanisms and structural data are expected to be revealed exponentially in this rapid growing realm.
Impact of trivalent ions on the stability and cohesion of calcium polyphosphate coacervates for embolization applications
Authors: Valliant Esther Mae , Filiaggi Mark Joseph 
Published: March 2019

AbstractPolyphosphates (PPs) are of interest as temporary in situ setting embolic agents for which cohesive characteristics are vital. Trivalent ions Al3+ and Ga3+ were substituted into calcium PP up to 10 mol % for two PP chain lengths (degree of polymerization, Dp 200 and 9000) and the effect on the dissolution rate of the resulting coacervate was examined. High levels of trivalent ions were found to increase the dissolution rate, especially with aluminum (Al) where the coacervate with the greatest Al content (10 mol %) and larger Dp completely dissolved within the first few hours in tris(hydroxymethyl)aminomethane buffered saline. Conversely, small amounts of trivalent ions slowed the dissolution rate of the coacervates compared to those containing calcium only. The coacervate compositions determined to have the fastest and slowest ion release were evaluated for cohesion upon injection into a simulated blood vessel using a dual lumen needle. PPs with lower trivalent content had a higher coacervate yield overall, with 5% Ga and Dp 200 yielding the smallest proportion of coacervate particulates that could be implicated in unwanted distal embolization. However, further studies are required to evaluate the formation and duration of occlusions in vivo so that the PP composition can best be tailored to meet clinical requirements. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2638–2648, 2019.
Methylation analysis highlights novel prognostic criteria in human‐metastasized melanoma
Authors: Cai Weiyang , Ding Xiaoxia , Li Jingjing , Li Zhiming 
Published: March 2019

AbstractMelanoma accounts for 90% of the deaths associated with cutaneous neoplasms, and the 5‐year survival rate of patients with the advanced stage is about 20%. Many mechanisms are involved in melanoma progression, but dynamic epigenetic changes are likely to be critical contributors, especially for DNA methylation. However, we know little about the methylation events involved in melanoma lymph node metastasis (LNM), a deficit that is of particular concern because it has a growing incidence and mortality. To identify DNA methylated‐associated changes involved in the formation of metastatic melanoma, we explored the different methylated genes (DMGs) between primary and LNM melanoma by Illumina Human Methylation 450 K BeadArray GSE44661. By integrating DNA methylation and messenger RNA expression data from The Cancer Genome Atlas database, we identified these DNA methylation biomarkers. Pathway analysis highlighted these DMGs, which were closely related to the carcinogenesis of melanoma, such as cell cycle regulation and RNA transcription process. Furthermore, according to the univariate and multivariate Cox regression analysis, we constructed a four‐DMG prognostic signature model, which could precisely predict the outcome of melanoma in a more exact way. In summary, this four‐DMG based risk score model successfully predicts the survival of melanoma. It is independent of other clinical characteristics and is good for prognosis prediction.
Inhibition of tyrosine kinases protects against lipopolysaccharide‐induced acute lung injury by preventing nuclear export of Nrf2
Authors: Duan Jiaxiang , Yang Zhen , Huang Jian , Zhu Yuan , Zhao Hailin , Unwith Sandeep , Gao Xian , Lu Kaizhi , Ning Jiaolin 
Published: March 2019

AbstractAcute Lung Injury is a common severe pathological condition that is usually caused by lipopolysaccharide (LPS) infection from bacteria. Enhanced activity of nuclear factor erythroid 2–related factor 2 (Nrf2) could attenuate LPS induced lung injury, However, it still remains unknown whether the enhanced activity of Nrf2 via suppression of Nrf2 nucleus export attenuates the LPS induced lung injury. The aim of this study is to investigate the effects of inhibitors of Fyn on the LPS‐induced acute lung injury and to explore its underlying molecular mechanisms. Nrf2 localization in the cells was observed by using confocal microscopy and its transcriptional activation was measured by Electrophoretic Mobility Shift Assay and controlled genes expression levels. The lung injury severity was examined by histopathological scoring and oxidative stress level. In this study, we showed that PP2, LMB, and Nrf2 Y568A abrogated Nrf2 nuclear export and thus enhance the Nrf2 transcriptional activity. PP2 attenuated lung injury and the reduction of cells viability induced by LPS. The current study demonstrated, for the first time, that increase of expression of Nrf2 controlled protective genes via suppression of Nrf2 nucleus export could attenuate lung injury.
Mitigative effects of the bioactive flavonol fisetin on high‐fat/high‐sucrose induced nonalcoholic fatty liver disease in rats
Authors: Gaballah Hanaa H. , El‐Horany Hemat E. , Helal Duaa S. 
Published: March 2019

AbstractBackgroundWorldwide growing rates of obesity are correlated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD) with limited available therapeutics.AimThe present study was undertaken to investigate the modulatory effects of dietary supplementation fisetin on hepatocyte nuclear factor 4 α (HNF4α) gene expression, hepatic lipin‐1 signaling, thioredoxin‐interacting protein (TXNIP) levels, poly‐(ADP‐ribose)‐polymerase‐1 (PARP‐1) activity, as well as some oxidative stress parameters in a rat model of high‐fat/high‐sucrose (HFHS) induced NAFLD.MethodsSixty male albino rats were allocated into four equal groups: normal control group, fisetin‐treated control group, NAFLD group, and fisetin‐treated NAFLD group. Gene expression levels of HNF4‐α were estimated using quantitative real‐time reverse transcription polymerase chain reaction (RT‐PCR), while Lipin‐1, TXNIP levels, and PARP‐1 activity were estimated by enzyme‐linked immunosorbent assay (ELISA); lipid profile, hepatic lipid contents, hepatic lipoperoxides, fatty acid synthase activity, and total antioxidant capacity were also assessed colorimetrically.ResultsFisetin ameliorated HFHS‐induced NAFLD; where it suppressed hepatic lipid accumulation, upregulated HNF4‐α /lipin‐1 signaling, mitigated oxidative stress, inhibited reactive oxygen species (ROS)‐mediated TXNIP induction, and PARP‐1 activation
. In conclusion, fisetin could confer protection against NAFLD and impede its progression. However,additional experimental scrutiny is needed to verify these findings.
Transcription factor FOXP3: A repressor of the TFPI gene?
Authors: Skretting Grethe , Andersen Elisabeth , Myklebust Christiane F. , Sandset Per Morten , Tinholt Mari , Iversen Nina , Stavik Benedicte 
Published: March 2019

AbstractSingle nucleotide polymorphisms (SNPs) may play an important role in the risk of certain diseases. We have previously shown that the ‐287T/C SNP of the tissue factor pathway inhibitor (TFPI) gene promoter region exerts differential impact on TFPI mRNA expression; the C allele being associated with higher TFPI expression, which in turn is associated with reduced risk of thrombosis. In the present study, we aimed to reveal the underlying molecular mechanisms using human embryonic kidney 293 (HEK293) and Michigan Cancer Foundation‐7 (MCF7) cells that both express TFPI. Transfecting the cells with luciferase reporter gene constructs containing the TFPI promoter with either the T or the C allele of ‐287T/C resulted in increased luciferase activity with the C allele relative to the T allele. Three potential candidate transcription factors for binding to the two ‐287 alleles were predicted using the ALGGEN PROMO software, and results from electrophoretic mobility shift assays indicated that forkhead box protein 3 (FOXP3), initially identified as a functional marker of T regulator cells, bound more specifically to the T allele compared with the C allele. By chromatin immunoprecipitation assays analysis it was confirmed that FOXP3 was able to bind to the DNA region that contains the SNP. Knockdown or overexpression of FOXP3 resulted in increased or decreased TFPI levels, respectively, in both cell types. In conclusion, this study indicates that FOXP3 most likely is involved in the increased levels of TFPI observed with the ‐287C allele and also that FOXP3 might be a repressor for TFPI expression.
Evaluation of global laboratory methods and establishing on‐therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution
Authors: Park Soon Ho , Seo Yiel‐Hea , Park Pil‐Whan , Kim Kyung‐Hee , Seo Ja Young , Lee Hwan Tae , Kwoun Woo‐Jae , Ahn Jeong‐Yeal 
Published: March 2019

BackgroundApixaban and rivaroxaban are approved for the prevention and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and embolic stroke in atrial fibrillation (AF) patients. The aim of this study was to find appropriate methods of monitoring the anticoagulant effects of are direct oral anticoagulants (DOACs) and establish on‐therapy ranges using conventional tests.MethodsA total of 184 samples were collected from 91 patients receiving DOACs. Concentrations of apixaban and rivaroxaban in plasma were accessed by an anti‐factor Xa chromogenic assay. PT, APTT, antithrombin, D‐dimer, dRVVT screen/confirm, FDP, and fibrinogen levels were measured. On‐therapy ranges were calculated by substituting previously reported trough plasma concentrations of DOACs.ResultsAnti‐factor Xa chromogenic assay‐based DOACs levels were 26.0‐279.5 (115.9 ± 56.5) ng/mL for apixaban at 2.5 mg BID, 19.9‐565.1 (205.3 ± 162.4) ng/mL for apixaban at 5 mg BID, 2.3‐395.3 (205.3 ± 162.4) ng/mL for rivaroxaban at 15 mg OD, 3.6‐494.8 (119.6 ± 95.1) ng/mL for rivaroxaban at 20 mg OD, and 9.6‐431.4 (140.8 ± 113.6) ng/mL for rivaroxaban at 15 mg BID. PT (%), antithrombin, and dRVVT confirm tests showed good correlation with plasma apixaban levels. Plasma rivaroxaban concentrations were correlated well with PT (sec), PT (%),and dRVVT confirm results. On‐therapy ranges established for dRVVT confirm test by linear regression were as follows: 1.32‐1.52 for apixaban 2.5 mg BID, 1.12‐1.75 for apixaban 5 mg BID, 1.11‐1.78 for rivaroxaban 15 mg OD, 1.09‐1.64 for rivaroxaban 20 mg OD, and 1.22‐1.81 for rivaroxaban 20 mg BID.ConclusionsApixaban concentrations were well correlated with PT (%), antithrombin, and dRVVT confirm test. Rivaroxaban concentrations showed good correlation with PT (sec), PT (%), and dRVVT confirm test.
Comparison of the Pharmacokinetic Properties of Naloxone Following the Use of FDA‐Approved Intranasal and Intramuscular Devices Versus a Common Improvised Nasal Naloxone Device
Authors: Krieter Philip A. , Chiang C. Nora , Gyaw Shwe , McCann David J. 
Published: March 2019

AbstractFor more than a decade, first responders and the general public have been able to treat suspected opioid overdoses using an improvised nasal naloxone device (INND) constructed from a prefilled syringe containing 2 mg of naloxone (1 mg/mL) attached to a mucosal atomization device. In recent years, the U.S. Food and Drug Administration (FDA)–approved Ezvio, an autoinjector that delivers 2 mg by intramuscular injection and Narcan nasal spray (2‐ and 4‐mg strengths; 0.1 mL/dose) for the emergency treatment of a known or suspected opioid overdose. The present study was conducted to compare the pharmacokinetics of naloxone using the FDA‐approved devices (each administered once) and either 1 or 2 administrations using the INND. When naloxone was administered twice using the improvised device, the doses were separated by 2 minutes. The highest maximum plasma concentration was achieved using the 4‐mg FDA‐approved spray. The highest exposures at 5 minutes postdose, based on AUC values, were after administration with the autoinjector and the 4‐mg FDA‐approved spray; at 10, 15, and 20 minutes postdose, the latter yielded the greatest exposure. Even after 2 administrations, the INND failed to achieve naloxone plasma levels comparable to the FDA‐approved devices at any time. The ease of use and higher plasma concentrations achieved using the 4‐mg FDA‐approved spray, compared with the INND, should be considered when deciding which naloxone device to use.
Taxonomic study of subfamily Nepetoideae (Lamiaceae) by polynomorphological approach
Authors: Gul Saba , Ahmad Mushtaq , Zafar Muhammad , Bahadur Saraj , Sultana Shazia , Begum Najla , Shah Syed Nasar , Zaman Wajid , Ullah Fazal , Ayaz Asma , Hanif Uzma 
Published: March 2019

AbstractThe present study is insight into pollen morphology for characterizing species and their utility in the taxonomic separation of certain taxa of subfamily Nepetoideae (Lamiaceae) from Pakistan. The pollen micromorphology of 11 species of the Nepetoideae was analyzed and documented using light microscopy and scanning electron microscopy (SEM) for both qualitative and quantitative characteristics. Most species have hexazonocolpate pollen grains but trizonocolpate and tetrazonocolpate pollen with circular and oval amb were also rarely observed in Mentha spicata. The basic pollen shape in most of the studied species was subspheroidal but prolate grains were also observed in M. spicata, S. coccinea, and S. plebeia. The exine sculpturing of Nepetoideae pollen was taxonomically very informative particularly at subfamily level. Observations of exine sculpturing with SEM revealed various types of pollen grains: reticulate, bireticulate, microreticulate, perforate, aerolate, and gammate. The bireticulate type further subdivided into three subtypes based on the number of secondary lumina in each primary lumen and is characterized by varying characteristics of the secondary reticulum and primary muri. A significant variation was observed in colpus surface ornamentation. The maximum polar diameter was found in O. americanum (58 ± 5.8 μm) and the maximum equatorial diameter observed in O. basilicum (50.25 ± 1.37 μm). Pollen features of the studied species were discussed and compared based on the current taxonomical concepts. The results showed that pollen traits of the subfamily Nepetoideae was found significant to classify the taxa. Furthermore, pollen features provide additional evidence to distinguish macromorphologically similar taxa from each other.
Change in serum levels of inflammatory markers reflects response of percutaneous catheter drainage in symptomatic fluid collections in patients with acute pancreatitis
Authors: Mallick Bipadabhanjan , Tomer Shallu , Arora Sunil K , Lal Anupam , Dhaka Narendra , Samanta Jayanta , Sinha Saroj K , Gupta Vikas , Yadav Thakur Deen , Kochhar Rakesh 
Published: March 2019

BackgroundPercutaneous catheter drainage (PCD) is used as the first step in the management of symptomatic fluid collections in patients with acute pancreatitis (AP). There are limited data on the effect of PCD on inflammatory markers.AimTo study the effects of PCD on serum levels of C‐reactive protein (CRP), IL‐6, and IL‐10 and its correlation with the outcome.MethodsConsecutive patients of AP with symptomatic fluid collections undergoing PCD were evaluated for serum levels of CRP, IL‐6, and IL‐10 before PCD and at 3 and 7 days after PCD. Resolution of organ failure (OF), sepsis, and pressure symptoms was considered to demonstrate the success of PCD. Changes in levels following PCD were correlated with outcome.ResultsIndications of PCD in 59 patients (age 38.9 ± 13.17 years, 49 male) were suspected/documented infected pancreatic necrosis (n = 45), persistent OF (n = 40), and pressure symptoms (n = 7). A total of 49 (83.1%) patients improved with PCD, five patients required surgery, and six died. A significant difference was noted between baseline levels of CRP (P = 0.026) and IL‐6 (P = 0.013) among patients who improved compared to those who worsened following PCD. Significant decrease (P < 0.01) of all three markers on day 3 of PCD insertion, with further decrease (P < 0.01) on day 7, was noted. The percentage of the decrease of IL‐6 levels on day 3 and of CRP on day 7 correlated with the outcome.ConclusionPCD is associated with a significant decrease in CRP, IL‐6, and IL‐10 levels. Percentage decrease in IL‐6 on day 3 and CRP on day 7 correlated with the outcome of patients managed with PCD.
A survey on the study of real zeros of flow polynomials
Authors: Dong Fengming 
Published: March 2019

AbstractFor a bridgeless graph , its flow polynomial is defined to be the function , which counts the number of nonwhere‐zero ‐flows on an orientation of whenever is a positive integer and is an additive Abelian group of order . It was introduced by Tutte in 1950, and the locations of zeros of this polynomial have been studied by many researchers. This paper gives a survey on the results and problems on the study of real zeros of flow polynomials.
Biophysical regulation of macrophages in health and disease
Authors: Meli Vijaykumar S , Veerasubramanian Praveen K , Atcha Hamza , Reitz Zachary , Downing Timothy L , Liu Wendy F 
Published: March 2019

Abstract
Macrophages perform critical functions for homeostasis and immune defense in tissues throughout the body. These innate immune cells are capable of recognizing and clearing dead cells and pathogens, and orchestrating inflammatory and healing processes that occur in response to injury. In addition, macrophages are involved in the progression of many inflammatory diseases including cardiovascular disease, fibrosis, and cancer. Although it has long been known that macrophages respond dynamically to biochemical signals in their microenvironment, the role of biophysical cues has only recently emerged. Furthermore, many diseases that involve macrophages are also characterized by changes to the tissue biophysical environment. This review will discuss current knowledge about the effects of biophysical cues including matrix stiffness, material topography, and applied mechanical forces, on macrophage behavior. We will also describe the role of molecules that are known to be important for mechanotransduction, including adhesion molecules, ion channels, as well as nuclear mediators such as transcription factors, scaffolding proteins, and epigenetic regulators. Together, this review will illustrate a developing role of biophysical cues in macrophage biology, and also speculate upon molecular targets that may potentially be exploited therapeutically to treat disease.
Short‐duration post CT‐guided thoracic biopsy monitoring‐ clinical experience with 440 patients
Authors: Frimpong George Asafu Adjaye , Aboagye Evans , Amankwah Pierre , Coleman Nana E. , Abaidoo Nakao K. 
Published: March 2019

AbstractPurposeWith several studies recording a higher percentage of complications in the first hour of post‐biopsy, this study sought to evaluate the safety in the reduction in post‐biopsy patient monitoring time after computed tomography (CT)‐guided thoracic biopsies, providing a basis for further research.Materials and MethodsThis was a retrospective study involving patients who were referred to our centre for CT‐guided thoracic biopsies from January 2010 to December 2017. Patients who presented with no complications immediately after the post‐biopsy CT scan were given 30 min of post‐biopsy care after which they were discharged, and given a hot line to call in case of any complication. There was also a follow‐up call by a nurse after 24 h to inquire about any complication and general condition of the patients.ResultsA total of 440 core needle thoracic biopsies were performed within the period of the study. The most common thoracic region indicated for biopsy was mediastinal (n = 240, 54.5%), followed by lung (n = 185, 42.0%). Complications were recorded at a rate of 6.4% (n = 28), with 4.1% (n = 18) been pneumothorax and pulmonary haemorrhage and haemoptysis accounting for 2.3% (n = 10). No relevant complications were recorded in patients who presented with no complications immediately after the post‐biopsy CT scan (n = 374, 85%).ConclusionsFindings from this initial study have shown that thirty minutes of post‐biopsy care could be sufficient for patients present with no complications immediately after a post‐procedural scan in CT‐guided thoracic biopsies; providing a basis for similar algorithms to be explored in a randomised control study to substantiate the observation.
Long‐Term Use of Mixed‐Oil Lipid Emulsion in Soybean Oil–Intolerant Home Parenteral Nutrition Patients
Authors: Mundi Manpreet S. , Kuchkuntla Aravind R. , Salonen Bradley R. , Bonnes Sara , Hurt Ryan T. 
Published: March 2019

AbstractBackground: Although home parenteral nutrition (HPN) is lifesaving for patients with chronic intestinal failure (IF), long‐term use can be associated with complications such as infections, metabolic abnormalities, and IF–associated liver disease (IFALD). The key to treatment of many of these complications is prevention. Guidelines recommend avoidance of overfeeding, use of oral/enteral nutrition if possible, cyclic PN, and maintaining dose of soybean oil (SO) intravenous lipid emulsion (ILE) <1 g/kg/day as preventive strategies for IFALD. Additionally, with development of IFALD, ω‐6/ω‐3 polyunsaturated fatty acid ratio should be decreased in ILE. The newly available mixed‐oil (MO) ILE offers such an opportunity; however, there is a paucity of long‐term data available. Methods: The current study reports our long‐term experience with MO ILE use in HPN patients. Results: Seventeen patients (8 female and 9 male) with an average age of 47 ± 12 years and median HPN duration of 4.6 years (1.1–32.1 years) have utilized MO ILE for >12 months after being transitioned from SO ILE because of intolerance. Use of MO ILE allowed an increase in ILE energy from 8% ± 8% to 22% ± 8% while reducing dextrose energy from 66% ± 8% to 54% ± 5%, maintaining stability in alkaline phosphatase and triglyceride levels, and achieving improvement in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and α‐tocopherol levels. Conclusion: In this HPN cohort with SO ILE intolerance, MO ILE was well tolerated and allowed an improvement in macronutrient composition while improving some liver parameters over a 12‐month period.