bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the role of mechanics in lignocellulosic biomass degradation during hydrolysis: Part II
Authors: Digaitis Ramūnas , Thybring Emil Engelund , Thygesen Lisbeth Garbrecht 
Published: September 2020

AbstractLignocellulose breakdown in biorefineries is facilitated by enzymes and physical forces. Enzymes degrade and solubilize accessible lignocellulosic polymers, primarily on fiber surfaces, and make fibers physically weaker. Meanwhile physical forces acting during mechanical agitation induce tearing and cause rupture and attrition of the fibers, leading to liquefaction, that is, a less viscous hydrolysate that can be further processed in industrial settings. This study aims at understanding how mechanical agitation during enzymatic saccharification can be used to promote fiber attrition. The effects of reaction conditions, such as substrate and enzyme concentration on fiber attrition rate and hydrolysis yield were investigated. To gain insight into the fiber attrition mechanism, enzymatic hydrolysis was compared to hydrolysis by use of hydrochloric acid. Results show that fiber attrition depends on several factors concerning reactor design and operation including drum diameter, rotational speed, mixing schedule, and concentrations of fibers and enzymes. Surprisingly, different fiber attrition patterns during enzymatic and acid hydrolysis were found for similar mixing schedules. Specifically, for tumbling mixing, slow continuous mixing appears to function better than faster, intermittent mixing even for the same total number of drum revolutions. The findings indicate that reactor design and operation as well as hydrolysis conditions are key to process optimization and that detailed insights are needed to obtain fast liquefaction without sacrificing saccharification yields.
RETRACTED: GANT61 plays antitumor effects by inducing oxidative stress through the miRNA‐1286/RAB31 axis in osteosarcoma
Authors: Zhang Kuai‐qiang , Chu Xiang‐dong 
Published: September 2020

AbstractOsteosarcoma (OS) is a rare malignancy of bone associated with poor clinical outcomes. The antitumor effects of GANT61 on OS is unclear. To investigate antitumor effects and mechanism of GANT61 in OS cells and xenograft model. Effects of GANT61 on cell viability, clone formation, cell cycle, apoptosis, migration, and invasion ability of OS cells were assessed. Reactive oxygen species (ROS) levels measured by dichlorofluorescein fluorescence were used to evaluate oxidative stress. The Xenograft model was constructed to investigate the antitumor effects of GANT61 in vivo. The microRNA (miRNA)‐1286 was downregulated, while RAB31 upregulated in OS tissues and cells. GANT61 inhibited viability, migration, and invasion ability of OS cells (SaOS‐2 and U2OS), and induced apoptosis and the ROS production, along with miRNA‐1286 upregulation and RAB13 downregulation. After knockdown of miRNA‐1286, GANT6‐induced cell inhibition was attenuated, along with RAB31 upregulation. Inversely, miRNA‐1286 overexpression downregulated RAB31. Dual‐luciferase reporter assay verified that miR‐1286 negatively targeted RAB13. Moreover, the knockdown of RAB31 stimulated apoptosis and ROS production while inhibited viability, migration, and invasion of GANT61‐treated cells. In vivo experiments further confirmed that GANT61 inhibited tumor growth and RAB13 expression, but enhanced miRNA‐1286. The study demonstrated that GANT61 inhibited cell aggressive phenotype and tumor growth by inducing oxidative stress through the miRNA‐1286/RAB31 axis. Our findings provided a potential antitumor agent for the OS clinical treatment.
A new perspective in CTO PCI
Authors: Rodriguez‐Paz Enrique , Heuser Richard R. 
Published: September 2020

Key Points
Comparative studies of CTO PCI versus medical therapy have not shown consistent benefits of intervention.
Interventional treatment of CTO takes more time, manual dexterity, device utilization, and results in a potential of increase in complications compared to non‐CTO PCI.
As experience and equipment evolve, PCI of CTO has dramatically improved.
Applied pharmacology in percutaneous coronary intervention: You can't fight mother nature
Authors: Bengaluru Jayanna Manju , Gray William A. 
Published: September 2020

Key Points
Differential outcomes based on target vessel diameter persist in the era of second generation drug eluting stents.
These differences are mainly driven by need for target vessel revascularization without appreciable differences in hard atherosclerotic cardiovascular disease outcomes that is, mortality and myocardial infarction.
Future non mechanistic treatment options based on patient characteristics maybe needed.
Left atrial function, the cherrie on top in understanding clinical outcomes in functional mitral regurgitation
Authors: Zahr Firas , Cigaarroa Joaquin E. 
Published: September 2020

Key Points
Left atrial function, as assessed by global longitudinal strain (GLS), is an important predictor of mortality and morbidity.
In patients with severe mitral regurgitation (MR) with reduced left ventricular systolic function (LVEF), effective treatment of the MR by mitral clip did not result in favorable left atrial or LV remodeling.
Despite effective and sustained treatment of MR, left ventricular diastolic pressure continued to increase during the follow‐up period.
Intravascular lithotripsy in calcified‐coronary lesions: A real‐world observational, European multicenter study
Authors: Aziz Amir , Bhatia Gurbir , Pitt Michael , Choudhury Anirban , Hailan Ahmed , Upadhyaya Subramanya , Lee Leong , Testa Luca , Casenghi Matteo , Ielasi Alfonso , Cortese Bernardo , Rides Hannah , Basavarajaiah Sandeep 
Published: September 2020

AbstractBackgroundThe recently introduced intravascular lithotripsy (IVL) appears promising and relatively safer than conventional approaches when dealing with calcified lesions. Although there are published reports on this novel technology, data from the real world are limited. In this study, we aim to report on the experience of IVL from a real‐world population derived from six European centers that undertake high‐volume complex coronary interventions.Methods and resultsWe enrolled all patients treated with IVL between November 2018 and February 2020 at six centers. Procedural success and complications were assessed along with clinical outcomes, which included: cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR), and major adverse cardiac event (MACE) (composite of cardiac death, TVMI, and TLR).Hundred and ninety patients (200 lesions) with a mean age of 72 years were treated using IVL. Diabetes and chronic kidney disease were present in 50% (n = 95) and 16% (n = 30) of cases, respectively. Acute‐coronary syndromes accounted for 91 (48%) of the cases. Most were de‐novo lesions (77%; n = 154). Upfront use of IVL occurred in 26% of cases, while the rest were bail‐out procedures due to inadequate predilatation with conventional balloons. Adjuvant rotational atherectomy was needed in 17% of cases. Procedural success was achieved in 99% of cases with a complication rate of 3%. During the median follow‐up of 222 days, there was two cardiac deaths (1%), one case of TVMI (0.5%), 3 TLR (1.5%) taking the MACE rate to 2.6%.ConclusionUse of IVL appears to be safe and effective in dealing with calcified‐coronary lesions. A high success rate was observed with low procedural complications and event rates.
Looking Back: A Short History of the Discovery of Enzymes and How They Became Powerful Chemical Tools
Authors: Heckmann Christian M. , Paradisi Francesca 
Published: September 2020

AbstractEnzymatic approaches to challenges in chemical synthesis are increasingly popular and very attractive to industry given their green nature and high efficiency compared to traditional methods. In this historical review we highlight the developments across several fields that were necessary to create the modern field of biocatalysis, with enzyme engineering and directed evolution at its core. We exemplify the modular, incremental, and highly unpredictable nature of scientific discovery, driven by curiosity, and showcase the resulting examples of cutting‐edge enzymatic applications in industry.
Mechanistic Insights into Fe Catalyzed α‐C−H Oxidations of Tertiary Amines
Authors: Legacy Christopher J. , Hope Taylor O. , Gagné Yohann , Greenaway Frederick T. , Frenette Mathieu , Emmert Marion H. 
Published: September 2020

AbstractWe report detailed mechanistic investigations of an iron‐based catalyst system, which allows the α‐C−H oxidation of a wide variety of amines. In contrast to other catalysts that effect α‐C−H oxidations of tertiary amines, the system under investigation exclusively employs peroxy esters as oxidants. More common oxidants (e. g. tBuOOH) previously reported to affect amine oxidations via free radical pathways do not provide amine α‐C−H oxidation products in combination with the described catalyst system. The investigations described herein employ initial rate kinetics, kinetic profiling, DFT calculations as well as Eyring, kinetic isotope effect, Hammett, ligand coordination, and EPR studies to shed light on the Fe catalyst system. The obtained data suggest that the catalytic mechanism proceeds through C−H abstraction at a coordinated substrate molecule. This rate‐determining step occurs either through an Fe(IV) oxo pathway or a 2‐electron pathway at an Fe(II) intermediate with bound oxidant. DFT calculations indicate that the Fe(IV) oxo mechanism will be the preferred route of these two possibilities. We further show via kinetic profiling and EPR studies that catalyst activation follows a radical pathway, which is initiated by hydrolysis of PhCO3tBu to tBuOOH. Overall, the obtained mechanistic data support a non‐classical, Fe catalyzed pathway that requires substrate binding, inducing selectivity for α‐C−H functionalization.
Si/SiOx Nanoparticles Embedded in a Conductive and Durable Carbon Nanoflake Matrix as an Efficient Anode for Lithium‐Ion Batteries
Authors: Nulu Arunakumari , Nulu Venugopal , Sohn Keun Y. 
Published: September 2020

AbstractIn this study, a route to synthesize a Si@SiOx/carbon nanoflake nanocomposite is proposed using ecological and polar solvent‐soluble ethyl cellulose as a promising new carbon source for obtaining silicon composites. Equal proportions of ethylcellulose and commercial nanosilicon powders are used to prepare the silicon/organic hybrid through an in situ chemical process, and the subsequent carbonization affords the Si@SiOx/C composite. The SiOx layer is partially formed using the employed method and air drying processes. As an anode electrode for lithium‐ion batteries (LIBs), the composite provides excellent reversible capacity (1830 mAh g−1 at 200 mA g−1 after 60 cycles) with 92 % capacity retention and superior rate performance (1464 mAh g−1 at 3.2 A g−1). The electrode with a high mass loading of 3.42 mg cm−2 delivered discharge capacities of 753 and 387 mAh g−1 at high current densities of 2 A g−1 and 4 A g−1, respectively. These results show that the coupling of silicon nanoparticles with an oxide layer and a conductive carbon framework is an effective design to retain the inherent properties of the silicon‐based anode, exhibiting its potential for use as a low‐cost anode for practical applications.
Overweight and obesity as protective factors against mortality in nonischemic cardiomyopathy patients with an implantable cardioverter defibrillator
Authors: Zhou Bin , Zhao Shuang , Tang Min , Chen Keping , Hua Wei , Su Yangang , Chen Silin , Liang Zhaoguang , Xu Wei , Li Xiaoyao , Xue Xiaodi , Sun Xuerong , Zhang Shu 
Published: September 2020

AbstractBackgroundPrevious studies have reported inconsistent results on the relationship between body mass index (BMI) and clinical outcomes in implantable cardioverter defibrillator (ICD) patients. Additionally, research on ICD patients with nonischemic cardiomyopathy (NICM) is lacking.HypothesisThis study aimed to investigate the impact of BMI on mortality and ventricular arrhythmias (VAs) in NICM patients with an ICD.MethodsThis study retrospectively analyzed the data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device‐implanted patients (SUMMIT) in China. Four hundred and eighty NICM patients with an ICD having BMI data were enrolled. Patients were divided into two groups: underweight and normal range group (BMI < 24 kg/m2), overweight and obese group (BMI≥24 kg/m2). The primary endpoint was all‐cause mortality. The secondary endpoint was the first occurrence of VAs requiring appropriate ICD therapy or shock.ResultsDuring a median follow‐up of 61 (1‐95) months, 70 patients (14.6%) died, 173 patients (36%) experienced VAs requiring appropriate ICD therapy, and 112 patients (23.3%) were treated with ICD shock. Multivariate Cox regression modeling indicated a decreased mortality risk in the overweight and obese group compared with the underweight and normal range group (hazard ratio = 0.44, 95% confidence interval 0.26‐0.77, P = .003). However, the risk of VAs was similar in both groups in univariate and multivariate Cox models.ConclusionsCompared with underweight and normal weight, overweight and obesity are protective against mortality but have only a neutral impact on VAs risk in NICM patients with an ICD.
Structure‐Activity Relationships of Benzamides and Isoindolines Designed as SARS‐CoV Protease Inhibitors Effective against SARS‐CoV‐2
Authors: Welker Armin , Kersten Christian , Müller Christin , Madhugiri Ramakanth , Zimmer Collin , Müller Patrick , Zimmermann Robert , Hammerschmidt Stefan , Maus Hannah , Ziebuhr John , Sotriffer Christoph , Schirmeister Tanja 
Published: September 2020

AbstractInhibition of coronavirus (CoV)‐encoded papain‐like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure‐activity relationships (SAR) of the noncovalent active‐site directed inhibitor (R)‐5‐amino‐2‐methyl‐N‐(1‐(naphthalen‐1‐yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS‐CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS‐CoV‐2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS‐CoV PLpro are valuable starting points for the development of new pan‐coronaviral inhibitors.
Synthesis and Structure‐Activity Relationships of 3‐Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors
Authors: Zhao Yitian , Xiong Yuan , Dong Sanfeng , Guan Xiaoqing , Song Yunqing , Yang Yanqing , Zou Kun , Li Zhao , Zhang Yong , Fang Shengquan , Li Bo , Zhu Weiliang , Chen Kaixian , Jia Qi , Ge Guangbo 
Published: September 2020

AbstractMammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3‐arylisoquinolones 3 h [3‐(4‐(benzyloxy)‐3‐methoxyphenyl)‐7,8‐dimethoxyisoquinolin‐1(2H)‐one] and 4 a [3‐(4‐(benzyloxy)‐3‐methoxyphenyl)‐4‐bromo‐7,8‐dimethoxyisoquinolin‐1(2H)‐one] were found to have potent inhibitory effects on hCES2A (IC50=0.68 μΜ, Ki=0.36 μΜ) and excellent specificity (more than 147.05‐fold over hCES1 A). Moreover, 4 a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3 h, with an IC50 value of 0.41 μΜ. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3 h and 4 a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure−activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.
Morphological and physiological properties of Rohon‐Beard neurons along the zebrafish spinal cord
Authors: Katz Hilary R. , Menelaou Evdokia , Hale Melina E. 
Published: September 2020

AbstractPrimary mechanosensory neurons play an important role in converting mechanical forces into the sense of touch. In zebrafish, Rohon‐Beard (RB) neurons serve this role at embryonic and larval stages of development. Here we examine the morphology and physiology of RBs in larval zebrafish to better understand how mechanosensory stimuli are represented along the spinal cord. We report that the morphology of RB neurons differs along the rostrocaudal body axis. Rostral RB neurons arborize in the skin near the cell body whereas caudal cells arborize at a distance posterior to their cell body. Using a novel electrophysiological approach, we also found longitudinal differences in the mechanosensitivity and physiological properties of RB neurons. Rostral RB neurons respond to mechanical stimulations close to the soma and produce up to three spikes with increasing stimulus intensity, whereas caudal cells respond at more distal locations and can produce four or more spikes when the intensity of the mechanical stimulus increases. The mechanosensory properties of RB neurons are consistent with those of rapidly adapting mechanoreceptors and can signal the onset, offset and intensity of mechanical stimulation. This is the first report of the intensity encoding properties of RB neurons, where an increase in spike number and a decrease in spike latency are observed with increasing stimulation intensity. This study reveals an unappreciated complexity of the larval zebrafish mechanosensory system and demonstrates how differences in the morphological and physiological properties of RBs related to their rostrocaudal location can influence the signals that enter the spinal cord.
Small Particle Fluorescence and Light Scatter Calibration Using FCMPASSSoftware
Authors: Welsh Joshua A. , Jones Jennifer C. 
Published: September 2020

AbstractUse of flow cytometry to analyze small particles has been implemented for several decades. More recently, small particle analysis has become increasingly utilized owing to the increased sensitivity of conventional and commercially available flow cytometers along with growing interest in small particles such as extracellular vesicles (EVs). Despite an increase in small particle flow cytometry utilization, a lack of standardization in data reporting has resulted in a growing body of literature regarding EVs that cannot be easily interpreted, validated, or reproduced. Methods for fluorescence and light scatter standardization are well established, and the reagents to perform these analyses are commercially available. Here, we describe FCMPASS, a software package for performing fluorescence and light scatter calibration of small particles while generating standard reports conforming to the MIFlowCyt‐EV standard reporting framework. This article covers the workflow of implementing calibration using FCMPASSas follows: acquisition of fluorescence and light scatter calibration materials, cataloguing the reference materials for use in the software, creating cytometer databases and datasets to associate calibration data and fcs files, importing fcs files for calibration, inputting fluorescence calibration parameters, inputting light scatter calibration parameters, and applying the calibration to fcs files. Published 2020. U.S. Government.Basic Protocol 1: Acquisition and gating of light scatter calibration materialsBasic Protocol 2: Acquisition and gating of fluorescence calibration materialsAlternate Protocol: Cross‐calibration of fluorescence reference materialsBasic Protocol 3: Cataloguing light scatter calibration materialsBasic Protocol 4: Cataloguing fluorescence calibration materialsBasic Protocol 5: Creating cytometer databases and datasetsBasic Protocol 6: Importing fcs filesBasic Protocol 7: Fluorescence calibrationBasic Protocol 8: Light scatter calibrationBasic Protocol 9: Performing and reporting fcs file calibration
Bioequivalence and Pharmacokinetic Evaluation of Two Metformin Hydrochloride Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers
Authors: Huang Xiao‐mei , Wang Gong‐zhu , He Bin‐bin , Gao Ting , Long Ping , Zhang Bi‐kui 
Published: September 2020

AbstractThis article aims to assess the bioequivalence of the test and the reference metformin hydrochloride tablets in healthy Chinese volunteers under fasting and fed conditions and to explore the effect of food on the pharmacokinetic (PK) profiles of both formulations. In total, 56 healthy Chinese subjects (28 in each group) were enrolled in this randomized, open, single‐center, single‐dose, 2‐treatment, 2‐sequence, 2‐cycle cross clinical trial. The subjects were administrated a single dose of the test and the reference tablets at 0.25 g with a 7‐day washout. Venous blood samples of all subjects were taken from predose 0 hour to postdose 24 hours according to the planned times. PK parameters for metformin were analyzed and calculated with noncompartmental methods. There were no significant differences in the PK parameters between the 2 formulations under both the fasting and the fed states. The 90% confidence intervals of 2 formulations were within 80.00%‐125.00% based on Cmax, AUC0‐t, and AUC0‐∞ under both conditions. High‐fat and high‐calorie diets delayed the Tmax and reduced the AUC0‐t and AUC0‐∞. No severe adverse events occurred in this study. Two metformin hydrochloride tablets were bioequivalent under both fasting and fed states; the high‐fat and high‐calorie diet could lower the rate and extent of absorption of metformin in healthy Chinese volunteers.
Antidepressant treatment in patients following acute coronary syndromes: a systematic review and Bayesian meta‐analysis
Authors: Sweda Romy , Siontis George C.M. , Nikolakopoulou Adriani , Windecker Stephan , Pilgrim Thomas 
Published: September 2020

AbstractAimsThe aim of this study is to investigate the effect of antidepressant therapy on mortality and cardiovascular outcomes in patients with acute coronary syndrome (ACS).Methods and resultsWe systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and performed a Bayesian random‐effects meta‐analysis of randomized controlled trials that investigated antidepressant pharmacotherapy in patients following ACS. The primary outcome was all‐cause mortality. Secondary outcomes were repeat hospitalizations and recurrent myocardial infarctions (MIs). Ten randomized controlled trials with a total of 1935 patients qualified for inclusion. Selective serotonin reuptake inhibitors were investigated in six, bupropion in three, and mirtazapine in one trial. Placebo was used as control in eight trials. There was no difference in all‐cause mortality [odds ratio (OR) 0.97, 95% credible interval (CrI) 0.66–1.42] and recurrent MI (OR 0.64, 95% CrI 0.40–1.02) between patients receiving antidepressants compared with controls, whereas antidepressant therapy was associated with less repeat hospitalizations (OR 0.62, 95% CrI 0.40–0.94). In patients with ACS and concomitant depression, antidepressants reduced the odds of recurrent MI compared with usual care/placebo (OR 0.45, 95% CrI 0.25–0.81). Extended funnel plots suggest robustness of the observations.ConclusionsAntidepressants in patients following ACS have no effect on mortality but reduce repeat hospitalizations; in patients with depression, there is a reduced risk of recurrent MI with antidepressant therapy.