bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery, Synthesis and Evaluation of a Ketol‐Acid Reductoisomerase Inhibitor
Authors: Bayaraa Tenuun , Kurz Julia L. , Patel Khushboo M. , Hussein Waleed M. , Bilyj Jessica K. , West Nicholas P. , Schenk Gerhard , McGeary Ross P. , Guddat Luke W. 
Published: March 2020

AbstractKetol‐acid reductoisomerase (KARI), the second enzyme in the branched‐chain amino acid biosynthesis pathway, is a potential drug target for bacterial infections including Mycobacterium tuberculosis. Here, we have screened the Medicines for Malaria Venture Pathogen Box against purified M. tuberculosis (Mt) KARI and identified two compounds that have Ki values below 200 nm. In Mt cell susceptibility assays one of these compounds exhibited an IC50 value of 0.8 μm. Co‐crystallization of this compound, 3‐((methylsulfonyl)methyl)‐2H‐benzo[b][1,4]oxazin‐2‐one (MMV553002), in complex with Staphylococcus aureus KARI, which has 56 % identity with Mt KARI, NADPH and Mg2+ yielded a structure to 1.72 Å resolution. However, only a hydrolyzed product of the inhibitor (i.e. 3‐(methylsulfonyl)‐2‐oxopropanic acid, missing the 2‐aminophenol attachment) is observed in the active site. Surprisingly, Mt cell susceptibility assays showed that the 2‐aminophenol product is largely responsible for the anti‐TB activity of the parent compound. Thus, 3‐(methylsulfonyl)‐2‐oxopropanic acid was identified as a potent KARI inhibitor that could be further explored as a potential biocidal agent and we have shown 2‐aminophenol, as an anti‐TB drug lead, especially given it has low toxicity against human cells. The study highlights that careful analysis of broad screening assays is required to correctly interpret cell‐based activity data.
MetaBridge: An Integrative Multi‐Omics Tool for Metabolite‐Enzyme Mapping
Authors: Blimkie Travis , Lee Amy Huei‐Yi , Hancock Robert E.W. 
Published: March 2020

AbstractMetaBridge is a web‐based tool designed to facilitate the integration of metabolomics with other “omics” data types such as transcriptomics and proteomics. It uses data from the MetaCyc metabolic pathway database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to map metabolite compounds to directly interacting upstream or downstream enzymes in enzymatic reactions and metabolic pathways. The resulting list of enzymes can then be integrated with transcriptomics or proteomics data via protein‐protein interaction networks to perform integrative multi‐omics analyses. MetaBridge was developed to be intuitive and easy to use, requiring little to no prior computational experience. The protocols described here detail all steps involved in the use of MetaBridge, from preparing input data and performing metabolite mapping to utilizing the results to build a protein‐protein interaction network. © 2020 by John Wiley & Sons, Inc.Basic Protocol 1: Mapping metabolite data using MetaCyc identifiersBasic Protocol 2: Mapping metabolite data using KEGG identifiersSupport Protocol 1: Converting compound names to HMDB IDsSupport Protocol 2: Submitting mapped genes produced by MetaBridge for protein‐protein interaction (PPI) network construction
Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS)
Authors: Lenders Malte , Nordbeck Peter , Kurschat Christine , Karabul Nesrin , Kaufeld Jessica , Hennermann Julia B. , Patten Monica , Cybulla Markus , Müntze Jonas , Üçeyler Nurcan , Liu Dan , Das Anibh M. , Sommer Claudia , Pogoda Christian , Reiermann Stefanie , Duning Thomas , Gaedeke Jens , Stumpfe Katharina , Blaschke Daniela , Brand Stefan‐Martin , Mann W. Alexander , Kampmann Christoph , Muschol Nicole , Canaan‐Kühl Sima , Brand Eva 
Published: March 2020

Fabry's disease (FD) is an X‐linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α‐galactosidase A (α‐Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous α‐Gal A activity. We assessed safety along with cardiovascular, renal, and patient‐reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under “real‐world” conditions. Fifty‐nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) with amenable mutations were recruited. Migalastat was generally safe and well tolerated. Females and males presented with a reduction of left ventricular mass index (primary end point) (−7.2 and −13.7 g/m2, P = 0.0050 and P = 0.0061). FD‐specific manifestations and symptoms remained stable (all P > 0.05). Both sexes presented with a reduction of estimated glomerular filtration rate (secondary end point) (−6.9 and −5.0 mL/minute/1.73 m2; P = 0.0020 and P = 0.0004, respectively), which was most prominent in patients with low blood pressure (P = 0.0271). α‐Gal A activity increased in male patients by 15% from 29% to 44% of the normal wild‐type activity (P = 0.0106) and plasma lyso‐Gb3 levels were stable in females and males (P = 0.3490 and P = 0.2009). Reevaluation of mutations with poor biochemical response revealed no marked activity increase in a zero activity background. We conclude that therapy with migalastat was generally safe and resulted in an amelioration of left ventricular mass. In terms of impaired renal function, blood pressure control seems to be an unattended important goal.
Load balancing by diversified quality factors‐based handoff (DQFH) in wireless cellular networks
Authors: Riyazuddien Shaik , Venkata Rao Dhulipalla , Ramarakula Madhu 
Published: March 2020

SummaryThe long‐term evolution (LTE) and long‐term evolution advance (LTE‐A) communication networks are the buzz of cellular networks. Due to the phenomenal count of users who hangs on cellular networks in regard to the concept of information and communications technology (ICT), the over‐sized demand of any network related to ICT experiences the crux of transmission load, which is critical constraint of the cellular networks. Though the contemporary research evincing the benchmark strategies to deal the crux of load on cellular networks, most of these are adapting handoff schemes to optimize the communication through effective load balancing under one or two standard quality metrics. Hence, the contemporary models have critical droppage in performance under the context of multiple quality objectives. In regard to deprive the constraints of the contemporary models, a handoff mechanism to optimize the load balancing in cellular networks under diversified contextual quality objectives has been defined in this manuscript. The method that is portrayed is a search technique that intends to select an optimal target node. The experimental study that was carried has evinced the significance the proposal that scaled against the contemporary methods having similar objective.
Medical comorbidities and endocrine dysfunction in low‐weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls
Authors: Aulinas Anna , Marengi Dean A. , Galbiati Francesca , Asanza Elisa , Slattery Meghan , Mancuso Christopher J. , Wons Olivia , Micali Nadia , Bern Elana , Eddy Kamryn T. , Thomas Jennifer J. , Misra Madhusmita , Lawson Elizabeth A. 
Published: March 2020

AbstractObjectiveTo improve our understanding of medical complications and endocrine alterations in patients with low‐weight avoidant/restrictive food intake disorder (ARFID) and how they may differ from those in anorexia nervosa (AN) and healthy controls (HC).MethodWe performed an exploratory cross‐sectional study comparing low‐weight females with ARFID (n = 20) with females with AN (n = 42) and HC (n = 49) with no history of an eating disorder.ResultsWe found substantial overlap in medical comorbidities and endocrine features in ARFID and AN, but with earlier onset of aberrant eating behaviors in ARFID. We also observed distinct medical and endocrine alterations in ARFID compared to AN, such as a greater prevalence of asthma, a lower number of menses missed in the preceding 9 months, higher total T3 levels, and lower total T4 : total T3 ratio; these differences persisted after adjusting for age and might reflect differences in pathophysiology, acuity of weight fluctuations, and/or nutritional composition of food consumed.ConclusionThese results highlight the need for prompt diagnosis and intensive therapeutic intervention from disease onset in ARFID.
Psychosocial factors, mental health symptoms, and disordered eating during pregnancy
Authors: Baskin Rachel , Meyer Denny , Galligan Roslyn 
Published: March 2020

AbstractObjectiveThe impact of disordered eating extends beyond women with a diagnosed eating disorder. Scarce research to date has investigated disordered eating in a general perinatal population, including the complex interplay between psychosocial factors, mental health symptoms, and disordered eating at numerous pregnancy periods. Specifically, maternal attitudes and relationship satisfaction are psychosocial factors that have been identified as a gap in the literature.MethodPregnant women completed an online questionnaire between 18 and 24 weeks gestation (T1, n = 258) and again between 30 and 32 weeks gestation (T2, n = 159). Structural equation modeling was used to test an interrelated model of psychosocial factors—attitudes to pregnancy, attitudes to motherhood, and relationship satisfaction—and disordered eating, mediated by either depressive or anxiety symptoms. Invariance testing examined whether model weights differed between primiparous and multiparous women at each time point.ResultsWhile at T1 and T2, there were significant direct associations between psychosocial factors and disordered eating, only at T2 were the associations between psychosocial factors and disordered eating mediated by depressive and anxiety symptoms. Furthermore, at T2, multiparous women were at greater risk of an association between maladaptive attitudes to pregnancy and motherhood, depressive symptoms, and disordered eating.DiscussionThe present study highlights the need to investigate the relationships between psychosocial factors and disordered eating, while accounting for the unique antenatal needs of women during different pregnancy periods and across differing parity. The mediating effect of depressive and anxiety symptoms have implications for future research and clinical care.
Organic matter reduces the amount of detectable environmental DNA in freshwater
Authors: van Bochove Kees , Bakker Freek T. , Beentjes Kevin K. , Hemerik Lia , Vos Rutger A. , Gravendeel Barbara 
Published: March 2020

AbstractEnvironmental DNA (eDNA) is used for monitoring the occurrence of freshwater organisms. Various studies show a relation between the amount of eDNA detected and target organism abundance, thus providing a potential proxy for reconstructing population densities. However, environmental factors such as water temperature and microbial activity are known to affect the amount of eDNA present as well. In this study, we use controlled aquarium experiments using Gammarus pulex L. (Amphipoda) to investigate the relationship between the amount of detectable eDNA through time, pH, and levels of organic material. We found eDNA to degrade faster when organic material was added to the aquarium water, but that pH had no significant effect. We infer that eDNA contained inside cells and mitochondria is extra resilient against degradation, though this may not reflect actual presence of target species. These results indicate that, although estimation of population density might be possible using eDNA, measured eDNA concentration could, in the future, be corrected for local environmental conditions in order to ensure accurate comparisons.
Nurse teachers’ knowledge about epilepsy and communication issues between schools and medical institutions: A nationwide questionnaire survey in Japan
Authors: Terada Kiyohito , Inoue Yushi , Nishida Takuji , Mishiro Daisuke , Yamano Mitsuhiko , Aoyagi Tomoo , Tadokoro Yuji 
Published: March 2020

AbstractObjectiveThe importance of school teachers’ knowledge of and attitudes toward epilepsy and the communication between educational and medical systems is widely appreciated, but exploration of these factors in Japan has been extremely limited. In order to identify issues in support systems for students with epilepsy and bridge the gaps in communication between schools and medical institutions in Japan, we performed a nationwide questionnaire survey of nurse teachers (nurses in charge of health education/care at schools).MethodsWe mailed a questionnaire to 900 nurse teachers all over Japan. It included six items on general epilepsy knowledge and 15 items on information about each student with epilepsy in their schools. We used a modified grounded theory approach (M‐GTA) to analyze open‐ended questions.ResultsWe received responses from 640 (71.1%) nurse teachers. In their schools, there were 237 253 students, of whom 1565 had epilepsy. Most nurse teachers (84.7%) understood that epilepsy is a neurological disease. When performing first aid for a seizure, they would observe the seizure calmly (85.9%) and/or secure the airway (75.3%). There were 1398 responses about individual students with epilepsy (89.3%). Nurse teachers knew the seizure type in 70.0% of these students, seizure frequency in 76.8%, triggers in 38.9%, and appropriate first aid for 79.0%. Some nurse teachers (30.2%) obtained information on students with epilepsy from medical institutions. They knew more about their students’ seizures than those without medical information. Existing forms for communicating information on students with epilepsy between schools and physicians were not actively utilized. Responses to open questions converged on safety at school.SignificanceJapanese nurse teachers understand epilepsy relatively well, but do not fully grasp the condition of each student with epilepsy. Better information flow from medical institutions is needed. Active communication is necessary to support the safety of students with epilepsy at school.
Formation mechanism of continuous gas leakage paths in cement sheath during hydraulic fracturing
Authors: Lian Wei , Li Jun , Tao Qian , Du Jinlong , Wang Lei , Xi Yan 
Published: March 2020

AbstractContinuous gas leakage paths of cement sheath during hydraulic fracturing were investigated in this study. The finite‐element models of a casing–cement‐sheath–formation assembly for the whole wellbore were established, the integrity of the cement sheath of the whole wellbore during single‐stage fracturing was analyzed firstly, and the factors affecting the integrity were examined. Furthermore, a cyclic compression test was conducted. Then, test results for the accumulative plastic strain of the cement sheath under the intermediate casing shoe during multistage fracturing were analyzed. Finally, the mechanism of dilatancy of cement stone in cyclic compression tests was analyzed. The results show that the radial and tangential stresses of the cement sheath increase and decrease, respectively, with depth. The cement sheath above the intermediate casing shoe had a risk of tensile failure, which could result in tangential tensile cracks. The cement sheath below the intermediate casing shoes had cumulative plastic strain, resulting in a microannulus. Reducing Young's modulus, increasing the Poisson ratio of the cement sheath, and reducing the pump pressure were beneficial to relieve the stress state. When the cyclic compressive stress exceeded the dilatation yield stress, the permeability increased with cycle numbers, and the increase in permeability provided another leakage path for gas migration.
Determination of water application rates required for communities to suppress post‐flashover informal settlement fires based on numerical modelling and experimental tests
Authors: Löffel Stefan A. , Walls Richard S. 
Published: March 2020

SummaryFires originating in informal settlements (ie, slums, ghettos, shantytowns, squatter camps) spread rapidly, due to the presence of densely packed, highly combustible dwellings, thereby making these communities inherently susceptible to large conflagrations. By the time, the fire brigades are notified and can get to the scene of the fire, the resulting conflagrations can be large. Thus, it is necessary to equip communities with the ability to combat smaller fires, although it is acknowledged that this is not ideal. Previous full‐scale testing and firefighter experience have shown that water application through ‘bucket brigades’ can be very effective at suppressing fires. In this article, a model is developed for approximately quantifying the amount of water, and discharge rate, that is, required for communities to suppress fires of various sizes using bucket brigades. This is done to answer the question: based on the water supply infrastructure in an area could a community put out post‐flashover fires of certain sizes? If this is not feasible, it would highlight the importance of communities having readily available pre‐filled water buckets at homes. The model presented is developed in fire dynamics simulator and is calibrated based on full‐scale experiments utilizing the bucket brigade technique. It is shown that standpipe discharge rates of 23 to 40 lpm are suitable for fire sizes of around 3.85 MW, based on a dwelling size of 2.4 x 3.6 x 2.4 m. This means that in communities with a single stand‐pipe (water supply point) with flow rates less than 23 lpm, that fires greater than 3.85 MW (as produced by a home of 2.4 x 3.6 m with a timber fuel load of 25 kg/m2) cannot be suppressed in time without resulting in substantial fire spread to adjacent dwellings.
Temperature assessment of steel members subjected to fire generated by alternative fuel vehicles: Experimental tests
Authors: Tramoni Jean‐Baptiste , Thauvoye Christophe , Hanus François , Poutrain Bruno , Suzanne Mathieu , Thiry Aurélien 
Published: March 2020

SummaryThis article aims at assessing the thermal action received by an unprotected steel structure during the combustion of alternative fuel vehicles. Five tests were realised in the underground of an airport hangar. To obtain a confinement effect and increase the probability of observing a thermal runaway of the traction battery, a second car was parked next to the alternative fuel vehicle. Five motorisations were tested: diesel fuel, H2 fuel cell, natural gas, electric, and liquefied petroleum gas. The diesel fuel car test served as reference case. The cars were located under a steel structure, representative of a car park, next to a wall. The wall served here to increase the confinement effect. Thirty‐nine sections of the structure were instrumented for a total of 200 thermocouples. An extensive analysis including fire behaviour for each test and comparisons between the tests is presented here.
Flame‐retardant properties and synergistic effect of ammonium polyphosphate/aluminum hydroxide/mica/silicone rubber composites
Authors: Hu Sheng , Tan Zhi‐Wei , Chen Fei , Li Jun‐Guo , Shen Qiang , Huang Zhi‐Xiong , Zhang Lian‐Meng 
Published: March 2020

SummaryThe flammability behaviors of ammonium polyphosphate/aluminum hydroxide/mica/silicone rubber (APP/Al[OH]3/mica/SiR) ceramifying composites containing APP, Al[OH]3, and mica are investigated by cone calorimeter test. The thermal degradation and the synergistic effect of APP/Al(OH)3/mica/SiR composites are investigated by thermal gravimetric analysis, X‐ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and X‐ray photoelectron spectroscopy. APP/Al(OH)3/mica/SiR composites with 25 wt% of APP, 20 wt% of Al(OH)3, 25 wt% of mica, and 30 wt% SiR presents a much lower total heat release, the value of peak heat release rate (PHRR), the maximum average heat release rate, the longest time to ignition, and time to the PHRR (tPHRR), compared with the flame‐retardant properties from composites with filler of APP and mica or APP and Al(OH)3 alone. The results indicate that there is an excellent synergism in APP, Al(OH)3, and mica, which endows APP/Al(OH)3/mica/SiR composites with both good flame retardancy and fire prevention. The study on the synergism effect between fire prevention and flame retardancy of APP/Al(OH)3/mica/SiR composites indicates that compounds containing P‐O‐Al are formed due to the reaction between APP and Al(OH)3 during combustion in the early stage and a coherent, dense, and sealed structure is formed due to the reaction in mica, phosphates, and the thermal decomposition products of SiR during combustion in the later stage.
Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group
Authors: Ho Tiffany C. , Gutman Boris , Pozzi Elena , Grabe Hans J. , Hosten Norbert , Wittfeld Katharina , Völzke Henry , Baune Bernhard , Dannlowski Udo , Förster Katharina , Grotegerd Dominik , Redlich Ronny , Jansen Andreas , Kircher Tilo , Krug Axel , Meinert Susanne , Nenadic Igor , Opel Nils , Dinga Richard , Veltman Dick J. , Schnell Knut , Veer Ilya , Walter Henrik , Gotlib Ian H. , Sacchet Matthew D. , Aleman André , Groenewold Nynke A. , Stein Dan J. , Li Meng , Walter Martin , Ching Christopher R. K. , Jahanshad Neda , Ragothaman Anjanibhargavi , Isaev Dmitry , Zavaliangos‐Petropulu Artemis , Thompson Paul M. , Sämann Philipp G. , Schmaal Lianne 
Published: March 2020

AbstractAlterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD‐related differences in subcortical regions using shape analysis. In this meta‐analysis of subcortical shape from the ENIGMA‐MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta‐analysis. Relative to CTL, patients with adolescent‐onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = −0.164 to −0.180). Relative to first‐episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = −0.173 to −0.184). Our results suggest that previously reported MDD‐associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.