bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substituted quinolinones. 31. Some new pyrano[3,2‐c]quinoline‐3‐carboxamides and their antioxidant activity
Authors: Othman Elham S. , Hassan Heba , Abass Mohamed 
Published: September 2019

Abstract1‐Ethyl‐4‐hydroxy‐2‐oxo‐1,2‐dihydroquinoline‐3‐carbaldehyde (1) was annulated using malonic acid and/or its ethyl ester to furnish pyrano[3,2‐c]quinoline‐3‐carboxylic acid 2 and its ester 3. Interconversions between acid 2 and ester 3 were successfully carried out. The anticipated pyrano[3,2‐c]quinoline‐3‐carboxamides 5–12 were conveniently attained via condensation of ester 3 with the proper amine. Surprisingly, treatment of ester 3 with dimethylformamide (DMF) in acidic media led to the carboxamide 5. All attempts to convert ester 3 to its corresponding acid hydrazides by interaction with the proper hydrazine derivative led to formation of pyrazolidinediones 15 and 17. Ester 3 underwent cyclo‐condensation with malononitrile dimer affording pyrido[3′,4′:5,6]pyrano[3,2‐c]quinoline derivative 18. The new compounds revealed significant antioxidant effect, which suggests that most of them are possible potent antioxidant agents.
Reactivity and stereoselectivity of oxazolopyridines with a ring‐junction nitrogen atom
Authors: Monier Mohamed , Abdel‐Latif Doaa , El‐Mekabaty Ahmed , Elattar Khaled M. 
Published: September 2019

AbstractThe present study demonstrates a synopsis of the scientific researches reported on the different reactions of oxazolo[3,2‐a]pyridines, besides the preparation of significant fused heterocycles up till now. The different main sections that described the reactivity of the inspected analogues include stereoselective alkylation, reactions involved oxazolidine ring, synthesis of polycyclic systems, indole alkaloids, and alkyl amines. The stereochemical selectivity of oxazolopiperidone lactams is studied, in which the configuration of the stereocenter C8a and substituents at the C8 and C8a effect on the stereoselectivity. On the other hand, the synthetic consequence of the alkylation products provides diverse routes for the synthesis of substituted enantiopure piperidines that are used for the synthesis of natural products, for example, (−)‐rhazinilam, (+)‐eburnamonine, (+)‐aspidospermidine, indole alkaloids such as dihydrocleavamine, nor‐20‐epiuleine, (+)‐dasycarpidone, (+)‐uleine, indoloquinolizidine, (+)‐dihydrocorynantheine, (−)‐dihydrocorynantheol, and indolizines, eg, octahydroindolizines, monomorine I, (−)‐S‐coniceine, and (−)‐R‐coniceine.
Dietary restriction of tyrosine and phenylalanine lowers tyrosinemia associated with nitisinone therapy of alkaptonuria
Authors: Hughes Juliette H. , Wilson Peter J. M. , Sutherland Hazel , Judd Shirley , Hughes Andrew T. , Milan Anna M. , Jarvis Jonathan C. , Bou‐Gharios George , Ranganath Lakshminarayan R. , Gallagher James A. 
Published: September 2019

AbstractAlkaptonuria (AKU) is caused by homogentisate 1,2‐dioxygenase deficiency that leads to homogentisic acid (HGA) accumulation, ochronosis and severe osteoarthropathy. Recently, nitisinone treatment, which blocks HGA formation, has been effective in AKU patients. However, a consequence of nitisinone is elevated tyrosine that can cause keratopathy. The effect of tyrosine and phenylalanine dietary restriction was investigated in nitisinone‐treated AKU mice, and in an observational study of dietary intervention in AKU patients. Nitisinone‐treated AKU mice were fed tyrosine/phenylalanine‐free and phenylalanine‐free diets with phenylalanine supplementation in drinking water. Tyrosine metabolites were measured pre‐nitisinone, post‐nitisinone, and after dietary restriction. Subsequently an observational study was undertaken in 10 patients attending the National Alkaptonuria Centre (NAC), with tyrosine >700 μmol/L who had been advised to restrict dietary protein intake and where necessary, to use tyrosine/phenylalanine‐free amino acid supplements. Elevated tyrosine (813 μmol/L) was significantly reduced in nitisinone‐treated AKU mice fed a tyrosine/phenylalanine‐free diet in a dose responsive manner. At 3 days of restriction, tyrosine was 389.3, 274.8, and 144.3 μmol/L with decreasing phenylalanine doses. In contrast, tyrosine was not effectively reduced in mice by a phenylalanine‐free diet; at 3 days tyrosine was 757.3, 530.2, and 656.2 μmol/L, with no dose response to phenylalanine supplementation. In NAC patients, tyrosine was significantly reduced (P = .002) when restricting dietary protein alone, and when combined with tyrosine/phenylalanine‐free amino acid supplementation; 4 out of 10 patients achieved tyrosine <700 μmol/L. Tyrosine/phenylalanine dietary restriction significantly reduced nitisinone‐induced tyrosinemia in mice, with phenylalanine restriction alone proving ineffective. Similarly, protein restriction significantly reduced circulating tyrosine in AKU patients.
Influence of Hamstrings on Knee Moments During Loading Response of Gait in Individuals Following ACL Reconstruction
Authors: Lin Paige E. , Sigward Susan M. 
Published: September 2019

ABSTRACTBiomechanical studies consistently report smaller knee extensor moments in the surgical limb during loading response (LR) of gait following ACL reconstruction (ACLr). However, this reduction in knee loading is quantified by net joint moments (NJM). As a result, in the presence of greater hamstring activity, the true contribution from the knee extensors may not be reduced. The purpose of this study is to compare hamstring activity and strength and knee joint moments between individuals post‐ACLr and controls. Eighteen individuals 3 months post‐ACLr and matched controls walked and net knee extensor moment peak and impulse and hamstring activity were identified during LR, as well as maximal hamstring strength. A hybrid musculoskeletal model estimated knee flexor moments from joint kinematics and hamstring electromyography. Flexor moments (SIMM) were scaled based on strength. Knee extensor moments were estimated from the sum of the net knee moment and estimated knee flexor moment; estimated extensor moment peaks and impulse were calculated during LR. Repeated measures analysis of variance compared groups and limbs. Smaller net knee extensor moment and greater hamstring activity, as well as deficits in maximal hamstring strength, were observed in the surgical limb (allp < 0.05). When accounting for the torque‐producing capabilities of the knee flexors, estimated knee extensor moment peak and impulse were smaller in the surgical limb. These findings suggest that net knee moments accurately reflect smaller knee extensor loading post‐ACLr. Statement of Clinical Significance: Rehabilitation programs should target increasing knee extensor loading to restore gait mechanics during early rehabilitation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:378‐386, 2020
Selective Sebaceous Gland Electrothermolysis Using a Single Microneedle Radiofrequency Device for Acne Patients: A Prospective Randomized Controlled Study
Authors: Ahn Ga Ram , Kim Jae Min , Park Su Jung , Li Kapsok , Kim Beom Joon 
Published: September 2019

Background and ObjectivesThe selective electrothermolysis of the sebaceous glands was suggested as a novel therapeutic option for facial acne. However, there has been no randomized controlled trial to evaluate the effectiveness and safety of the monopolar radiofrequency (RF) device using single microneedle with proximal insulation. The objective of the study was to evaluate the efficacy and tolerability of intralesional electrothermolysis using monopolar RF device and proximally‐insulated single microneedle in acne patients.Study Design/Materials and MethodsThe prospective randomized controlled clinical trial was performed to treat moderate‐to‐severe facial acne. Subjects randomized to the treatment group received three treatments at 4‐week intervals with an RF device, whereas the control group received micro‐needling and extraction. For efficacy evaluation, reduction rate of acne lesions were evaluated by two independent physicians.ResultsSixty‐three patients completed the study and the results showed statistically significant improvement of inflammatory acne at 12 weeks. The number of inflammatory lesions was significantly reduced at 12 weeks (20.86 vs. −5.13; P = 0.03) compared with controls.ConclusionsSelective sebaceous gland electrothermolysis can be a safe and effective method of achieving consistent improvement in acne. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
I‐convexity and Q‐convexity in Orlicz–Bochner function spaces endowed with the Orlicz norm
Authors: Gong Wanzhong , Dong Xiaoli , Wang Kangji 
Published: September 2019

AbstractSome characterizations of I‐convexity and Q‐convexity of Banach space are obtained. Moreover, the criteria is shown for Orlicz–Bochner function spaces endowed with the Orlicz norm being I‐convex as well as being Q‐convex.
Higher Urine bis(Monoacylglycerol)Phosphate Levels in LRRK2 G2019S Mutation Carriers: Implications for Therapeutic Development
Authors: Alcalay Roy N. , Hsieh Frank , Tengstrand Elizabeth , Padmanabhan Shalini , Baptista Marco , Kehoe Caitlin , Narayan Sushma , Boehme Amelia K. , Merchant Kalpana 
Published: September 2019

AbstractBackgroundLRRK2 mutations are a common cause of dominantly inherited PD. Previous studies showed decreases in urine levels of didocohexaenoyl (22:6) bis(monoacylglycerol)phosphate in LRRK2‐knockout mice and in non‐human primates treated with LRRK2 kinase inhibitors. We hypothesized that urine levels of bis(monoacylglycerol)phosphate isoforms will be higher in individuals with a PD‐causing gain‐of‐kinase function mutation, LRRK2 G2019S. The objective of this study was to investigate alterations in urinary phospholipids as biomarkers of LRRK2 mutations and Parkinson's disease status/phenotypes.MethodsUltra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) was used to assess 54 bioactive phospholipids in urine from the LRRK2 Cohort Consortium (n = 80). To confirm and extend the findings, urine from an independent LRRK2 cohort from Columbia University Irving Medical Center (n = 116) was used. Both cohorts were composed of LRRK2 G2019S carriers and non‐carriers with and without PD.ResultsIn each cohort, 4 bis(monoacylglycerol)phosphate isoforms (di‐18:1‐bis[monoacylglycerol]phosphate, didocohexaenoyl [22:6] bis[monoacylglycerol] phosphate, 2,2′‐di‐22:6‐bis[monoacylglycerol]phosphate, and 2,2′‐di‐18:1‐bis[monoacylglycerol]phosphate) were significantly higher (2.5‐ to 4.3‐fold) in G2019S carriers compared with non‐carriers. Interestingly, 2,2′‐di‐18:1‐bis(monoacylglycerol)phosphate levels were marginally higher in LRRK2 carriers with PD than in those without PD (P = 0.045). Moreover, increased 2,2′ and total di‐22:6‐bis(monoacylglycerol)phosphate were associated with worse cognitive status assessed by the Montreal Cognitive Assessment (P = 0.0033 and 0.0144, respectively).ConclusionsThe observed association of bis(monoacylglycerol)phosphate isoforms with LRRK2 G2019S mutation, PD status among G2019S carriers, and correlation with cognitive decline suggest the potential use of urinary bis(monoacylglycerol)phosphate isoforms as biomarkers for clinical trials of LRRK2‐targeted therapies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Inducible nitric oxide synthase inhibitors: A comprehensive update
Authors: Minhas Richa , Bansal Yogita , Bansal Gulshan 
Published: September 2019

AbstractInducible nitric oxide synthase (iNOS), which is expressed in response to bacterial/proinflammatory stimuli, generates nitric oxide (NO) that provides cytoprotection. Overexpression of iNOS increases the levels of NO, and this increased NO level is implicated in pathophysiology of complex multifactorial diseases like Parkinson's disease, Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Selective inhibition of iNOS is an effective approach in treatment of such complex diseases. l‐Arginine, being a substrate for iNOS, is the natural lead to develop iNOS inhibitors. More than 200 research reports on development of nitric oxide synthase inhibitors by different research groups across the globe have appeared in literature so far. The first review on iNOS, in 2002, discussed the iNOS inhibitors under two classes that is, amino acid and non‐amino acid derivatives. Other review articles discussing specific chemical classes of iNOS inhibitors also appeared during last decade. In the present review, all reports on both natural and synthetic iNOS inhibitors, published 2002 onwards, are studied, classified, and discussed to provide comprehensive information on iNOS inhibitors. The synthetic inhibitors are broadly classified into two categories that is, arginine and non‐arginine analogs. The latter are further classified into amidines, five‐ or six‐membered heterocyclics, fused cyclics, steroidal type, and chalcones analogs. Structures of the most/significantly potent compounds from each report are provided to know the functional groups important for incurring iNOS inhibitory activity and selectivity. This review is aimed to provide a comprehensive view to the medicinal chemists for rational designing of novel and potent iNOS inhibitors.
Analysis of miRNA‐mRNA regulatory network revealed key genes induced by aflatoxin B1 exposure in primary human hepatocytes
Authors: Zhang Ziyang , Tang Dongyang , Wang Bin , Wang Zhiwei , Liu Mingjiu 
Published: September 2019

AbstractBackgroundAflatoxin B1 (AFB1) exposure is a crucial factor to initiate hepatocellular carcinoma (HCC). However, comprehensive microRNA (miRNA)‐message RNA (mRNA) regulatory network regarding AFB1‐associated HCC is still lacking. This work was aimed to identify miRNA‐mRNA network in primary human hepatocytes after AFB1 exposure.MethodsA miRNA expression dataset GSE71540 obtained from the gene expression omnibus (GEO) was used to identify differentially expressed miRNAs (DEMs) after AFB1 exposure using GEO2R. Target genes of these DEMs were identified using TargetScan V_7.2, miRDB, PITA, miRanda, and miRTarBase. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed at Database for Annotation, Visualization and Integrated Discovery (DAVID). miRNA‐mRNA regulatory network was established by analyzing three enriched KEGG pathways significantly correlated with HCC onset and then visualized at CytoScape.ResultsIn this work, nine upregulated and nine downregulated DEMs were identified. Functional enrichment analyses showed that these predicted target genes were significantly associated with cancer development. Analysis of three enriched pathways related to the onset of HCC identified 13 and nine target genes for upregulated DEMs and downregulated DEMs, respectively. Subsequently, the miRNA‐mRNA regulatory networks were constructed.ConclusionsIn conclusion, miRNA‐mRNA regulatory network was established, which will help to understand the mechanism underlying the AFB1‐induced onset of HCC.
Automatic detection of contouring errors using convolutional neural networks
Authors: Rhee Dong Joo , Cardenas Carlos E. , Elhalawani Hesham , McCarroll Rachel , Zhang Lifei , Yang Jinzhong , Garden Adam S. , Peterson Christine B. , Beadle Beth M. , Court Laurence E. 
Published: September 2019

PurposeTo develop a head and neck normal structures autocontouring tool that could be used to automatically detect the errors in autocontours from a clinically validated autocontouring tool.MethodsAn autocontouring tool based on convolutional neural networks (CNN) was developed for 16 normal structures of the head and neck and tested to identify the contour errors from a clinically validated multiatlas‐based autocontouring system (MACS). The computed tomography (CT) scans and clinical contours from 3495 patients were semiautomatically curated and used to train and validate the CNN‐based autocontouring tool. The final accuracy of the tool was evaluated by calculating the Sørensen–Dice similarity coefficients (DSC) and Hausdorff distances between the automatically generated contours and physician‐drawn contours on 174 internal and 24 external CT scans. Lastly, the CNN‐based tool was evaluated on 60 patients' CT scans to investigate the possibility to detect contouring failures. The contouring failures on these patients were classified as either minor or major errors. The criteria to detect contouring errors were determined by analyzing the DSC between the CNN‐ and MACS‐based contours under two independent scenarios: (a) contours with minor errors are clinically acceptable and (b) contours with minor errors are clinically unacceptable.ResultsThe average DSC and Hausdorff distance of our CNN‐based tool was 98.4%/1.23 cm for brain, 89.1%/0.42 cm for eyes, 86.8%/1.28 cm for mandible, 86.4%/0.88 cm for brainstem, 83.4%/0.71 cm for spinal cord, 82.7%/1.37 cm for parotids, 80.7%/1.08 cm for esophagus, 71.7%/0.39 cm for lenses, 68.6%/0.72 for optic nerves, 66.4%/0.46 cm for cochleas, and 40.7%/0.96 cm for optic chiasm. With the error detection tool, the proportions of the clinically unacceptable MACS contours that were correctly detected were 0.99/0.80 on average except for the optic chiasm, when contours with minor errors are clinically acceptable/unacceptable, respectively. The proportions of the clinically acceptable MACS contours that were correctly detected were 0.81/0.60 on average except for the optic chiasm, when contours with minor errors are clinically acceptable/unacceptable, respectively.ConclusionOur CNN‐based autocontouring tool performed well on both the publically available and the internal datasets. Furthermore, our results show that CNN‐based algorithms are able to identify ill‐defined contours from a clinically validated and used multiatlas‐based autocontouring tool. Therefore, our CNN‐based tool can effectively perform automatic verification of MACS contours.
Cluster analysis of time evolution (CAT) for quantitative susceptibility mapping (QSM) and quantitative blood oxygen level‐dependent magnitude (qBOLD)‐based oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) mapping
Authors: Cho Junghun , Zhang Shun , Kee Youngwook , Spincemaille Pascal , Nguyen Thanh D. , Hubertus Simon , Gupta Ajay , Wang Yi 
Published: September 2019

PurposeTo improve the accuracy of QSM plus quantitative blood oxygen level‐dependent magnitude (QSM + qBOLD or QQ)‐based mapping of the oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) using cluster analysis of time evolution (CAT).Methods3D multi‐echo gradient echo and arterial spin labeling images were acquired in 11 healthy subjects and 5 ischemic stroke patients. DWI was also carried out on patients. CAT was developed for analyzing signal evolution over TE. QQ‐based OEF and CMRO2 were reconstructed with and without CAT, and results were compared using region of interest analysis and a paired t‐test.ResultsSimulations demonstrated that CAT substantially reduced noise error in QQ‐based OEF. In healthy subjects, QQ‐based OEF appeared less noisy and more uniform with CAT than without CAT; average OEF with and without CAT in cortical gray matter was 32.7 ± 4.0% and 37.9 ± 4.5%, with corresponding CMRO2 of 148.4 ± 23.8 and 171.4 ± 22.4 μmol/100 g/min, respectively. In patients, regions of low OEF were confined within the ischemic lesions defined on DWI when using CAT, which was not observed without CAT.ConclusionThe cluster analysis of time evolution (CAT) significantly improves the robustness of QQ‐based OEF against noise.
Single‐Voxel 1H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD+) in humans at 7T using a 32‐channel volume coil
Authors: Bagga Puneet , Hariharan Hari , Wilson Neil E. , Beer Joanne C. , Shinohara Russell T. , Elliott Mark A. , Baur Joseph A. , Marincola Francesco M. , Witschey Walter R. , Haris Mohammad , Detre John A. , Reddy Ravinder 
Published: September 2019

PurposeReliable monitoring of tissue nicotinamide adenine dinucleotide (NAD+) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a 1H MRS pulse sequence for the in vivo, localized 1H MRS detection of NAD+ from the human brain.MethodsStudies were carried out on a 7T Siemens MRI scanner using a 32‐channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E‐BURP‐1 90° pulse. PRESS localization was achieved using optimized Shinnar‐Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD+ quantification was measured in 11 healthy volunteers. The association of cerebral NAD+ with age was assessed in 16 healthy subjects 26–78 years old.ResultsSpectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H2, H4, and H6 protons of the nicotinamide moiety of NAD+ between 8.9–9.35 ppm. The mean ± SD within‐session and between‐session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age‐dependent decline of the NAD+ levels in the brain was also observed (β = −1.24 μM/y, SE = 0.21, P < 0.001).ConclusionWe demonstrated the feasibility and robustness of a newly developed 1H MRS technique to measure localized cerebral NAD+ at 7T MRI using a commercially available RF head coil. This technique may be further applied to detect and quantify NAD+ from different regions of the brain as well as from other tissues.
The Effects of Regulated Area Location and Size on the Effectiveness of a Catch-and-Release Season for a Riverine Black Bass
Authors: Sammons Steven M. 
Published: September 2019

Abstract
Catch-and-release areas are an extension of the concept of aquatic protected areas, which implement protective measures at a broad spatial scale in an attempt to increase conservation efforts. Also, catch-and-release areas are commonly used to regulate sport fisheries, particularly in specific areas during the spawning season. However, the size and location of catch-and-release areas are rarely evaluated in terms of their effects on the success of these regulations in protecting these species. Empirical exploitation data were used with an age-structured model to explore changes in population biomass and size structure of Shoal Bass Micropterus cataractae in the Flint River, Georgia, with simulated changes in the location and size of catch-and-release areas during the spawning season. Annual exploitation of Shoal Bass with no catch-and-release area was 0.257 and was reduced 0–21% when a catch-and-release regulation was simulated in a specific reach. Models predicted significant increases in population biomass and size structure using catch-and-release reaches as short as 33 km, but this was contingent upon which specific reaches were designated as catch and release. As area size increased, population biomass and size structure of the population increased, but the rate of increase depended upon the specific areas incorporated. Designation of the entire reach would decrease annual exploitation by 50%, but large portions of the study area could be designated as catch and release with little changes in population biomass or size structure due to low harvest rates. This study illuminated the importance of spatial patterns of harvest in determining effectiveness of catch-and-release areas, which should be an important consideration in the placement of such aquatic protected areas.