bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidural Anesthesia in Liver Surgery—A Propensity Score–Matched Analysis
Authors: Knaak Cornelia , Spies Claudia , Schneider Alice , Jara Maximilian , Vorderwülbecke Gerald , Kuhlmann Anna Dorothea , von Haefen Clarissa , Lachmann Gunnar , Schulte Erika 
Published: April 2020

Abstract

Objective
To assess the effects of epidural anesthesia (EA) on patients who underwent liver resection.

Design
Secondary analysis of a prospective randomized controlled trial.

Setting
This single-center study was conducted at an academic medical center.

Methods
A subset of 110 1:1 propensity score–matched patients who underwent liver resection with and without EA were analyzed. Outcome measures were pain intensity ≥5 on a numeric rating scale (NRS) at rest and during movement on postoperative days 1–5, analyzed with logistic mixed-effects models, and postoperative complications according to the Clavien-Dindo classification, length of hospital stay (LOS), and one-year survival. One-year survival in the matched cohorts was compared using a frailty model.

Results
EA patients were less likely to experience NRS ≥5 at rest (odds ratio = 0.06, 95% confidence interval [CI] = 0.01 to 0.28, P &lt; 0.001). These findings were independent of age, sex, Charlson comorbidity index, baseline NRS, and surgical approach (open vs laparoscopic). The number and severity of postoperative complications and LOS were comparable between groups (P = 0.258, P &gt; 0.999, and P = 0.467, respectively). Reduced mortality rates were seen in the EA group one year after surgery (9.1% vs 30.9%, hazard ratio = 0.32, 95% CI = 0.11 to 0.90, P = 0.031). No EA-related adverse events occurred. Earlier recovery of bowel function was seen in EA patients.

Conclusions
Patients with EA had better postoperative pain control and required fewer systemic opioids. Postoperative complications and LOS did not differ, although one-year survival was significantly improved in patients with EA. EA applied in liver surgery was effective and safe.
EXPERIMENTAL DETERMINATION OF ANISOTROPIC EMISSION OF NEUTRONS FROM 252CF NEUTRON SOURCE WITH THE SPHERICAL PROTECTION CASE
Authors: Kowatari Munehiko , Nishino Sho , Romallosa Kristine Marie D , Yoshitomi Hiroshi , Tanimura Yoshihiko , Ohishi Tetsuya 
Published: April 2020

Abstract
The anisotropic emission of neutrons from a cylindrical X1 252Cf source with the spherical external casing was experimentally determined. The influence of metal materials and shapes of the external casing to the anisotropy factor, FI(θ), was assessed by the Monte Carlo calculation, before performing the measurement. The results of the calculation implied that light- and spherical-shaped external casing decreases the anisotropic emission of neutrons from a cylindrical source and the nature of the material does not affect the anisotropic emission to a large extent. The experimental results obtained when a spherical-shaped aluminum protection case was employed also revealed that the anisotropy factor was close to 1.0 with a wide zenith angle range. Considering the source handling and measures against mechanical impact to the source, we designed an SUS304-made spherical protection case for a renovated source delivering apparatus. With the SUS304-made spherical protection case, the measured anisotropy factor FI(90) was determined to be 1.002 ± 0.002 (k = 1). Results from the experiments also indicated that the measured anisotropy factor has a flat distribution from 55 to 125° with zenith angle.
A novel dark septate fungal endophyte positively affected blueberry growth and changed the expression of plant genes involved in phytohormone and flavonoid biosynthesis
Authors: Wu Fan-Lin , Li Yan , Tian Wei , Sun Yadong , Chen Feiyan , Zhang Yurou , Zhai Yuxuan , Zhang Jing , Su Hongyan , Wang Lei 
Published: April 2020

AbstractDark septate endophytes (DSEs) are one of the most studied groups of root fungal endophytes in recent years. However, the effects of DSE on host plant are still under debate, and the molecular mechanisms are poorly understood. In this study, we identified a DSE fungus of the genus Anteaglonium, named T010, from the wild blueberry. When inoculated into Vaccinium corymbosum L. plants, T010 could enhance root growth and promote shoot branching, leading to increased plant growth. By comparative transcriptome analysis, we obtained 1948 regulated differentially expressed genes (DEGs) from the V. corymbosum plants treated by T010. Further functional enrichment analysis identified a series of DEGs enriched in transcriptional regulation, material transport, phytohormone biosynthesis and flavonoid biosynthesis. Moreover, the comparative analysis of liquid chromatography–mass spectrometry verified that T010 treatment induced the changes in the contents of various phytohormones and flavonoids. This is the first report on the isolation of DSE fungi of the genus Anteaglonium from blueberry roots. Moreover, our results suggested that T010 colonization could result in a series of changes in cell metabolism, biosynthesis and signal pathways, thereby promoting plant growth. Particularly, the changes of phytohormone and flavonoid metabolism induced by T010 colonization might contribute to the promotion of blueberry growth. Our results will provide new insights into understanding of the interaction of DSE fungi and host plants, as well as the development and utilization of DSE preparations.
Sex Differences in Youth Elite Swimming
Authors: Clayburn Andrew , Senefeld Jonathon W , Baker Sarah E , Carter Rickey , Johnson Patrick , Joyner Michael J 
Published: April 2020

The timing and magnitude of sex differences in athletic performance during early human development, prior to adulthood, is unknown.ObjectiveTo compare swimming velocity of boys and girls for all Olympic‐length freestyle swimming events to determine the age of divergence in swimming performance.MethodsWe collected the all‐time top 100 U.S. freestyle swimming performance times of boys and girls age 5 to 18 years for the 50m to 1500m events.ResultsSwimming performance improved with increasing age for boys and girls (p<0.001) until reaching a plateau, which initiated at a younger age for girls (15 years) than boys (17 years; sex×age; p<0.001). Prior to age 10, the top 5 swimming records for girls were 3% faster than the top boys (p<0.001). For the 10th–50th places, however, there were no sex‐related differences in swimming performance prior to age 10 (p=0.227). For both the top 5 and 10th–50th places, the sex difference in performance increased from age 10 (top 5, 2.5%; 10th–50th places, 1.0%) until age 17 (top 5, 7.6%; 10th–50th places, 8.0%). For all places, the sex difference in performance at age 18 was larger for sprint events (9.6%; 50–200m) than endurance events (7.1%; 400–1500m; p<0.001). Additionally, the sex‐related difference in performance increased across age and US ranking from 2.4% for 1st place to 4.3% for 100th place (p<0.001), indicating less depth of performance in girls than boys. However, annual participation was ~20% higher in girls than boys for all ages (p<0.001).ConclusionThe top 5 girls demonstrated faster swimming velocities and the 10th–50th place girls demonstrated similar swimming velocities than boys (until ~10 years). After age 10, however, boys demonstrated increasingly faster swimming velocities than girls until 17 years. Collectively, these data suggest girls are faster, or at least not slower, than boys prior to the performance‐enhancing effects of puberty.Support or Funding InformationThis study was supported by the National Institutes of Health R‐35‐HL139854‐02 (MJJ), HL139854‐02S1 (AJC), 5T32DK007352‐40 (JWS), and the Mayo Foundation.Elite swimming performance.Mean swimming velocity from 5 to 18 years of the top 100 fastest US boys (blue circles) and girls (red triangles) for the 50, 100, 200, 400, 800 and 1500m freestyle swimming distances.Figure 1Sex differences in performance of the top 5 places.The primary plot (heat map) displays the sex differences in swimming velocity (% boy’s swimming velocity) of the top 5 US rankings in each freestyle event distance and age, negative values (red) indicate faster performance of girls. The top displays the mean sex difference across age, and the right plot displays the mean sex difference across swimming event distance.Figure 2
Resveratrol Attenuates Obesity‐ and Aging‐induced Sarcopenia Mitochondrial Dysfunction in Mice Skeletal Muscle.
Authors: Wu Jia-Ping 
Published: April 2020

Sarcopenic obesity is a progressive loss of skeletal muscle mass and strength with increases in adiposity. The aim of this study was to investigate the effects of resveratrol on obesity and sarcopenia to potential therapy risk for skeletal muscle decline in physical function. C57BL/6J male mice fed either a high‐fat diet for 4 weeks and resveratrol (low‐, middle‐, and high‐dose) for 8 weeks to express the obesity effect. SAMP8 mice sarcopenic skeletal muscle functional deterioration expressed an age‐associated decline. Resveratrol (150 mg/kgBW) was administered by oral gavage two times a week one month of the experimental period. Exercise training based on adaptations in the muscle is training twice a week for 4 weeks. The skeletal muscles from mice in each group were analyzed by H&E staining, TUNEL and western blot analysis to determine mitochondrial function expression, apoptosis and relative fibrosis signaling. Results of the present study indicate that resveratrol in obesity skeletal muscle is linked to an increase in the expression of mitochondrial function involved in Bcl‐2 and PI3K/AKT. On the other hand, resveratrol attenuates sarcopenic SAMP8 mice, the age‐related loss of skeletal muscle mass and mitochondrial function involved Bad, caspase 3 and IL‐6/ERK1. However, exercise training did not find a significant difference in sarcopenic skeletal muscles SAMP8 mice. Exercise training did not induce sarcopenic skeletal muscle hypertrophy in SAMP8 mice. Therefore, we suggest that resveratrol as a therapeutic potential in the combination of sarcopenia and obesity, the state called sarcopenic obesity.Support or Funding InformationFunding of this study was provided by the Ministry of science and technology (MOST 104‐2811‐B‐009‐007, MOST 105‐2811‐B‐039‐008, and MOST 106‐2811‐B‐650‐003)Schematic representation of the inhibition effects of resveratrol on obesity and aging sarcopenia. The mechanisms underlying the pathophysiology of sarcopenic obesity. In obesity skeletal muscle, adipocytes undergo hypertrophy activation resulted in skeletal muscle atrophy due to accumulation of pro‐inflammation as well as mitochondrial dysfunction together with senescent muscle cells. Skeletal muscle inflammation trigger and support sarcopenic obesity development.Figure 7
LFA‐9, a Selective Inhibitor of Microsomal Prostaglandin Synthase‐1 and 5‐Lipoxygenase: Prevention of Inflammatory and Oncologic Diseases
Authors: Yarla Nagendra Sastry , Pathuri Gopal , Gali Hariprasad , Panneerselvam Janani , Chandrakesan Parthasarathy , Madka Venkateshwar , Rao Chinthalapally V. 
Published: April 2020

Cyclooxygenase‐1 (COX‐1), COX‐2 and 5‐lipoxygenase (5‐LOX) as targets for inflammatory diseases and many agents were developed and extensively used in the clinic. Chronic use of drugs that target COX‐1/COX‐2 are associated with unwanted side effects including GI toxicity and cardiovascular risk. Hence, the main aim of this work is to develop mechanistic based safer agents that would target microsomal prostaglandin synthase‐1 (mPGES‐1) (a downstream enzyme of COX‐2) and 5‐LOX, while sparing COX‐1&‐2 activity. LFA‐9 was designed using structure‐based drug discovery and synthesized from licofelone by adding 2‐aminoethanoic acid (Glycine) at its carboxylic end that led to targeting mPGES‐1 and 5‐LOX but not COX‐1&2. In silico, in vitro and ex vivo studies on LFA‐9 were performed using human/mouse/rat mPGES‐1 and 5‐LOX to facilitate pre‐clinical experimentation and clinical translation. In the molecular docking studies, LFA‐9 showed strong binding affinity against 5‐LOX (binding energies range between −199.85 & −215.3 Kcal/mol) and mPGES‐1 (binding energies range between −238.27 & −257.76 Kcal/mol), but not with COX‐1&2. In cell free system studies, LFA‐9 substantially inhibited mPGES‐1 (range of IC50 between 0.52 – 1.40 μM) and 5‐LOX (range of IC50 between 0.89 – 2.75 μM) but not COX‐1&2 (IC50>1mM) when assayed using fluorometric and colorimetric methods. Moreover, LFA‐9 substantially inhibited PGE2 (IC50 range between 0.47 – 0.78 μM) and LTB4 (IC50 range between 0.56 – 1.24 μM) production and spared PGI2 (IC50>1 mM) and TXB2 (IC50>1 mM) production in LPS‐stimulated human/mouse/rat macrophages and whole blood as the cell‐based system using ELISA technique. Further, circular dichroism and isothermal calorimetric based studies demonstrated that LFA‐9 strongly binds and induces changes in secondary structure of human mPGES‐1 and 5‐LOX enzymes, thereby inhibits their activities. In addition, LFA‐9 (cLogP = 4.34) obeys Lipinsky’s rule of 5 for druglikeness and shows better water solubility unlike licofelone (cLogP = 6.15). Furthermore, LFA9 prevented tumor stemness of APC mutant colonic epithelial cells from PIRC rats in vitro and inhibited exogenous PGE2 in tumor like microenvironment. Therefore, LFA9 is a novel mPGES‐1 and 5‐LOX inhibitor and safer drug candidate for inflammatory and oncologic diseases.Support or Funding InformationAuthors acknowledged NIH/NCI R01CA 213987 and NIH/NCI HHSN261201500024I for funding support.Chemical structures of Licofelone and LFA9Figure 1
Identification of additive formulations for enhanced shelf‐life and productivity of E. coli cell‐free protein synthesis extracts
Authors: Gregorio Nicole E. , Kao Wesley Y. , Williams Layne C. , Patel Pratish A. , Watts Katharine R. , Oza Javin P. 
Published: April 2020

Cell‐Free Protein Synthesis (CFPS) is a platform biotechnology that enables a breadth of applications, from expressing traditionally intractable proteins to metabolic engineering and point‐of‐care diagnostics. However, field applications have remained limited due to the poor shelf stability of aqueous E. coli cell‐free extracts, which contain a complex mixture of cellular machinery. Lyophilization of the E. coli extract improves shelf‐life, but remains insufficient for maintaining extract productivity over extended storage periods at room temperature. For many pure protein‐based biologics, a variety of additives have been identified that help to stabilize the protein for lyophilization, transportation, and storage. However, the advances made for pure proteins cannot be directly applied to the complex cell extract, and current investigations into improving cell extract stability via additives has been limited. Thus, we have addressed the cold chain limitation in cell‐free by mapping the chemical space of ten low‐cost additives with four distinct mechanisms of action in a combinatorial manner to elucidate their capacity to further stabilize lyophilized cell extract. We report three key findings: 1) unique additive formulations that maintain full productivity of the cell extract at 4°C and 23°C; 2) additive formulations that enhance extract productivity up to 195%; 3) a machine learning algorithm that provides predictive capacity for the stabilizing effects of additive formulations that were not tested experimentally. The identified additive formulations provide a simple and low‐cost advance toward making CFPS field‐ready.Support or Funding InformationBill and Linda Frost Fund, Center for Applications in Biotechnology’s Chevron Biotechnology Applied Research Endowment Grant, Cal Poly Research, Scholarly, and Creative Activities Grant Program (RSCA 2017), and the National Science Foundation (NSF‐1708919)Comparison of traditional cellfree extract production and reaction setup with our modified workflow for improved stability and productivity to enable field applications.Figure 1
A Click Chemistry Approach to Reveal the chromatin‐Dependent Histone H3 K36 Deacetylase Nature of SIRT7
Authors: Liu Wenshe Ray , Wang Wesley Z. 
Published: April 2020

Using an engineered pyrrolysyl‐tRNA synthetase mutant together with tRNAPyl, we have genetically encoded Ne‐(7‐azidoheptanoyl)‐L‐lysine (AzHeK) by amber codon in Escherichia coli for recombinant expression of a number of AzHeK‐containing histone H3 proteins. We assembled in vitro acyl‐nucleosomes from these recombinant acyl‐H3 histones. All these acyl‐nucleosomes contained an azide functionality that allowed quick click labeling with a strained alkyne dye for in‐gel fluorescence analysis. Using these acyl‐nucleosomes as substrates and click labeling as a detection method, we systematically investigated chromatin deacylation activities of SIRT7, a class III NAD+‐dependent histone deacylase with roles in aging and cancer biology. Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. We further demonstrated that this H3K36 deacylation activity is nucleosome dependent and can be significantly enhanced when appending the acyl‐nucleosome substrate with a short double‐stranded DNA that mimics the bridging DNA between nucleosomes in native chromatin. By overexpressing SIRT7 in human cells, we verified that SIRT7 natively removes acetylation from histone H3K36. Moreover, SIRT7‐deficient cells exhibited H3K36 hyperacetylation in whole cell extracts, at rDNA sequences in nucleoli, and at select SIRT7 target loci, demonstrating the physiologic importance of SIRT7 in determining endogenous H3K36 acetylation levels. H3K36 acetylation has been detected at active gene promoters, but little is understood about its regulation and functions. Our findings establish H3K36 as a physiologic substrate of SIRT7 and implicate this modification in potential SIRT7 pathways in heterochromatin silencing and genomic stability.Support or Funding InformationNIH GM121584, NIH AG050997, NIH GM086703, Welch A‐1715Figure 1
A Module Swapping Approach to Engineer Allosterically Regulated Transcriptional Regulators
Authors: Chan Clement T.Y. 
Published: April 2020

Allosterically regulated transcriptional regulators are key biological components for genetic response to environmental signals. These proteins bind to DNA to control gene expression, and their interactions with DNA are regulated by molecular signals. Transcriptional regulators in the LacI family are composed of two discrete and sequence modules, in which one senses molecular signals (ligand‐binding module) and the other one interacts with promoters to regulate gene expression (DNA‐binding module). Recently, we demonstrated that these LacI family modules can be interchanged robustly to generate functional regulators. We swapped ligand‐binding modules and DNA‐binding modules among LacI family members. The resulting hybrid regulators possess a new combination of allosteric response and DNA recognition properties that are originated from the ligand‐binding module and DNA‐binding module, respectively. Additionally, we showed that this module swapping approach can also be applied to regulators in the TetR family to create a hybrid protein with desirable functions.These hybrid regulators enable flexible connections between environmental signals and genetic elements, which were harnessed to implement two genetic circuit designs that were previously infeasible. These genetic circuits include a programmable ‘Passcode’ genetic device, which potentially serves as a biocontainment system to limit the proliferation of engineered cells in a highly specific environment, preventing their spread to natural environments and enhancing biosafety. As another example, we have developed a system of Multiple Toggle Switches with a Master OFF signal, which enable the equipped cells to simultaneously monitor multiple biological and environmental traits.Overall, we have established a protein design principle for creating genetic regulatory elements that facilitate cell engineering. We demonstrated that these engineered parts are sufficient for generating new cellular behaviors for potential applications in biotechnology and biomedicine.Support or Funding InformationThis research is supported by National Science Foundation [MCB‐1914538], the University of Texas System Rising STARs Program, and the Welch Foundation [# BP‐0037].Allosterically regulated transcriptional regulators within the same protein family have ligand‐binding modules and DNA‐binding modules that are conserved, discrete, and functional. By combining the module that responds to effector A and the module that recognizes operator B, we can create a regulator enabling the use of effector A to control activities of promoter B, which is a new input‐output connection. These engineered regulators have been used to develop several genetic networks.Figure 1
Bioorthogonal Chemical Probes of Lysine Acetyltransferases
Authors: Zheng Y. George 
Published: April 2020

Acetylation of lysine residues is one of the most important posttranslational modifications that diversify protein functions. Thousands of acetylated lysine residues have been identified, suggesting that the effects of lysine acetyltransferases (KATs) go far beyond the chromatin kingdom. However, there is a missing link connecting the compositions of the cellular acetylome networks to the enzymatic activities of different KAT members. The outstanding challenge is how to dissect the subacetylomes of individual KATs and address their functions on the proteomic scale. We have explored a
bioorthogonal
profiling of
protein
acetylation strategy to label and interrogate substrates of KAT enzymes. In this strategy, a suite of Ac‐CoA analogs containing either alkynyl or azido functional group (e.g. 3AZ‐CoA, 4AZ‐CoA, 4PY‐CoA, 5HY‐CoA, 6HY‐CoA) were synthesized as potential cofactor surrogate for selective labeling of KAT substrates. Meanwhile, the active site of the KATs was engineered in order to expand the cofactor binding capability of the enzymes to accommodate the bulkier synthetic cofactors. The acylated substrates can be selectively linked through the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction with fluorescent reporter or biotin affinity tag for optical imaging or protein enrichment on streptavidin‐coated resin. We have successfully used this bioorthogonal technology to profile substrates of p300 and GCN5 in the context of complex cellular proteomes. Together with LC‐MS/MS technology, more than four hundred proteins were identified as GCN5 or p300 substrate candidates. These proteins are extensively involved in various biological events including gene expression, cell cycle, and cellular metabolism. Overall, we have invented a bioorthogonal, chemoproteomic technology to investigate KAT biology. This chemical biology strategy provides a powerful enabling technology for activity‐based lysine acylation profiling on proteomic scale. Indeed, our KAT activity profiling demonstrates extensive engagement of KATs in cellular pathways and provides new molecular insights into understanding their functions in epigenetics and other biological processes.bioorthogonal profilingFigure 1