bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel GJB1 mutation associated with X‐linked Charcot–Marie–Tooth disease in a large Chinese family pedigree
Authors: Liu Yingdi , Xue Jinjie , Li Zhuo , Linpeng Siyuan , Tan Hu , Teng Yanling , Liang Desheng , Wu Lingqian 
Published: January 2020

AbstractBackgroundCharcot–Marie–Tooth (CMT) disease is a group of hereditary neuropathies with high phenotypic and genetic heterogeneity. In this study, we report a large family with X‐linked CMT (CMTX) caused by a novel GJB1 mutation.MethodsA family with the clinical diagnosis of CMTX was investigated. For mutation analysis, the coding region of GJB1 was sequenced using DNA from 15 family members. The identified GJB1 mutation was investigated by DHPLC in 120 normal controls. Mutation reanalysis was performed based on whole‐exome sequencing (WES). Cell transfection studies were performed to characterize the function of the novel mutation.ResultsA missense mutation (c.605T>A) in GJB1 was detected in five patients and eight female carriers but not in two unaffected members of the family. The mutation was not found in 120 healthy controls and has not been previously reported. WES excluded other pathogenic mutations in the family. The pathogenicity of the mutation was confirmed by disrupting the membrane localization of the encoded proteins.ConclusionOur findings demonstrate that a novel mutation (c.605T>A) in GJB1 is associated with CMTX and adds to the repertoire of GJB1 mutations related to CMTX.
Plant‐ and Fish‐Derived n‐3 PUFAs Suppress Citrobacter Rodentium–Induced Colonic Inflammation
Authors: Määttänen Pekka , Lurz Eberhard , Botts Steven R. , Wu Richard Y. , Robinson Shaiya C. , Yeung C. William , Colas Romain , Li Bo , Johnson‐Henry Kathene C. , Surette Marc E. , Dalli Jesmond , Sherman Philip M. 
Published: January 2020

ScopeMarine‐derived n‐3 PUFAs may ameliorate inflammation associated with inflammatory bowel diseases. Plant‐derived n‐3 PUFAs are thought to be inferior owing to shorter chain lengths. The aim of this study is to compare the impact of plant‐ and fish‐derived PUFAs on murine colitis.Methods and resultsC57BL/6 mice are fed high fat (36% kcal) diets with either 2.5% w/w sunflower oil (SO), flaxseed oil (FSO), ahiflower oil (AO), or fish oil (FO). After 4 weeks, mice are orogastrically challenged with Citrobacter rodentium (108 CFU) or sham gavaged. Fecal shedding is assayed at 2, 7, 10, and 14 days post infection (PI), and fecal microbiota at 14 days PI. Colonic inflammation and lipid mediators are measured. Supplementation regulates intestinal inflammation with crypt lengths being 66, 73, and 62 ±17 µm shorter (compared to SO) for FSO, AO, and FO respectively, p < 0.01. FSO blunts pathogen shedding at the peak of infection and FSO and AO both enhance fecal microbial diversity. FO attenuates levels of lipoxin and leukotriene B4 while plant oils increase pro‐resolving mediator concentrations including D, E, and T‐series resolvins.ConclusionPlant and fish n‐3 PUFAs attenuate colitis‐induced inflammation while exhibiting characteristic pro‐resolving lipid mediator metabolomes. Plant oils additionally promote microbial diversity.
Plasma Phospholipids with Long‐Chain Polyunsaturated Fatty Acids and Dihydroceramides at the Crossroads of Iron Stores and Insulin Resistance
Authors: Mayneris‐Perxachs Jordi , Mousa Aya , Naderpoor Negar , Fernández‐Real José‐Manuel , de Courten Barbora 
Published: January 2020

ScopeIron plays an important role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. Recent studies suggest a role of specific lipids in the induction of IR, but the potential relationships between iron and lipid metabolites in relation to IR have not been explored. Therefore, the aim of the study is to evaluate the association among iron, IR, and the lipidome.Methods and resultsThe plasma lipidome, IR, parameters of iron metabolism, and several cytokines and adipokines in 65 overweight/obese participants are measured. Measurements of IR correlate positively with ferritin, a measure of iron storage (r = 0.35, p = 0.005), and negatively with adiponectin (r = −0.30, p = 0.02). The serum ferritin/adiponectin ratio has a stronger association with IR (r = 0.41, p < 0.001). From multivariate analyses adjusted for age, sex, and BMI, several phospholipids containing long chain polyunsaturated fatty acids (PUFA) with 20–22 carbons (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, and a phosphatidylserine), are positively associated with ferritin and the ferritin/adiponectin ratio. Two dihydroceramides (Cer(18:0/22:0), Cer(18:0/24:0)) and several diglycerides and triglycerides, mainly comprised of C14:0, C16:0, C18:0, C18:1, and C18:2, also have positive correlations with ferritin and the ferritin/adiponectin ratio.ConclusionsThe positive associations between these lipid species and ferritin or the ferritin/adiponectin ratio suggest a potential crosstalk between iron and lipid metabolism in obesity and IR.
Benchtop NMR analysis of piperazine‐based drugs hyperpolarised by SABRE
Authors: Tennant Thomas , Hulme Matthew C. , Robertson Thomas B.R. , Sutcliffe Oliver B. , Mewis Ryan E. 
Published: January 2020

AbstractPiperazine‐based drugs, such as N‐benzylpiperazine (BZP), became attractive in the 2000s due to possessing effects similar to amphetamines. Herein, BZP, in addition to its pyridyl analogues, 2‐, 3‐, and 4‐pyridylmethylpiperidine (2‐PMP, 3‐PMP, and 4‐PMP respectively) was subjected to the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE) in order to demonstrate the use of this technique to detect these piperazine‐based drugs. Although BZP was not hyperpolarised via SABRE, 2‐PMP, 3‐PMP, and 4‐PMP were, with the ortho‐ and meta‐pyridyl protons of 4‐PMP showing the largest enhancement of 313‐fold and 267‐fold, respectively, in a 1.4‐T detection field, following polarisation transfer at Earth's magnetic field. In addition to the freebase, 4‐PMP.3HCl was also appraised by SABRE and was found not to polarise, however, the addition of increasing equivalents of triethylamine (TEA) produced the freebase, with a maximum enhancement observed upon the addition of 3 equivalents of TEA. Further addition of TEA led to a reduction in the observed enhancement. SABRE was also employed to polarise 4‐PMP.3HCl (~20% w/w) in a simulated tablet to demonstrate the forensic application of the technique (138‐fold enhancement for the ortho‐pyridyl protons). The amount of 4‐PMP.3HCl present in the simulated tablet was quantified via NMR using D2O as a solvent and compared well to complimentary gas chromatography–mass spectrometry data. Exchanging D2O for CD3OD as the solvent utilised for analysis resulted in a significantly lower amount of 4‐PMP.3HCl being determined, thus highlighting safeguarding issues linked to drug abuse in relation to determining the amount of active pharmaceutical ingredient present.
Results from an international phase 2 study of the anti‐CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B‐lineage acute lymphoblastic leukemia
Authors: Shah Nirali N. , Bhojwani Deepa , August Keith , Baruchel André , Bertrand Yves , Boklan Jessica , Dalla‐Pozza Luciano , Dennis Robyn , Hijiya Nobuko , Locatelli Franco , Martin Paul L. , Mechinaud Françoise , Moppett John , Rheingold Susan R. , Schmitt Claudine , Trippett Tanya M. , Liang Meina , Balic Kemal , Li Xia , Vainshtein Inna , Yao Nai Shun , Pastan Ira , Wayne Alan S. 
Published: January 2020

AbstractBackgroundIn a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti‐CD22 immunotoxin, demonstrated a manageable safety profile and preliminary evidence of clinical activity. A phase 2 study further evaluated efficacy.ProcedureThis international, multicenter, phase 2 study enrolled children with relapsed/refractory B‐cell precursor ALL who received moxetumomab pasudotox 40 µg/kg intravenously every other day, for six doses per 21‐day cycle. The primary objective was to evaluate the complete response (CR) rate. Secondary objectives included safety, pharmacokinetics, and immunogenicity evaluations.ResultsThirty‐two patients (median age, 10 years) were enrolled at 16 sites; 30 received study drug and were evaluable for safety; 28 were evaluable for response. The objective response rate was 28.6%, with three patients (10.7%) achieving morphologic CR, and five patients (17.9%) achieving partial response. Disease progression occurred in 11 patients (39.3%). Ten patients (33.3%) experienced at least one treatment‐related serious adverse event, including capillary leak syndrome (CLS; n = 6), hemolytic uremic syndrome (HUS; n = 4), and treatment‐related death (n = 1) from pulmonary edema. No differences were observed in inflammatory markers in patients who did or did not develop CLS or HUS.ConclusionsDespite a signal for clinical activity, this phase 2 study was terminated at interim analysis for a CR rate that did not reach the stage 1 target. Preclinical data suggest enhanced efficacy of moxetumomab pasudotox via continuous infusion or in combination regimens; thus, further studies designed to optimize the efficacy and safety of moxetumomab pasudotox in pediatric ALL may be warranted.
High prevalence of parent‐reported sleep problems in pediatric patients with acute lymphoblastic leukemia after induction therapy
Authors: Steur Lindsay M. H. , Grootenhuis Martha A. , Van Someren Eus J. W. , Van Eijkelenburg Natasha K. A. , Van der Sluis Inge M. , Dors Natasja , Van den Bos Cor , Tissing Wim J. E. , Kaspers Gertjan J. L. , Van Litsenburg Raphaële R. L. 
Published: January 2020

AbstractObjectiveTo assess sleep problems (prevalence and predictors) in pediatric patients with acute lymphoblastic leukemia (ALL) after the most intensive phase of therapy (induction).MethodsPatients (≥2 years) treated according to the Dutch ALL‐11 protocol were included. Sleep was measured using parent‐reports and self‐reports (Children's Sleep Habits Questionnaire; CSHQ) and actigraphy. Parental sleep (Medical Outcome Study Sleep Scale) and distress and parenting problems (Distress Thermometer for Parents) were assessed with questionnaires. Z‐scores were calculated for total CSHQ scores using age‐appropriate scores of healthy Dutch children. The prevalence of sleep problems (defined as a Z‐score > 1) in patients with ALL was compared to healthy children (chi‐square tests). Actigraphic sleep estimates were collected in healthy Dutch children (n = 86, 2‐18 years) for comparison with patients (linear regression). Determinants of parent‐reported child sleep (total CSHQ Z‐score) were identified with regression models.ResultsResponses were collected for 124 patients (response rate 67%), comprising 123 parent‐reports, 34 self‐reports, and 69 actigraphy assessments. Parents reported sleep problems in 38.0% of the patients compared to 15.2% in healthy children (P < .001). Patients reported fewer sleep problems themselves: 12.1% compared to 15.8% in healthy children (P = .33). Total time in bed (B (95% CI): 22.89 (9.55‐36.22)) and total sleep time (B (95% CI):16.30 (1.40‐31.19)), as derived from actigraphy, were significantly longer in patients. More parent‐reported child sleep problems were predicted by parenting problems, more parental sleep problems, bedroom sharing, and child's sleep medication use (explained variance: 27.4%).ConclusionsSystematic monitoring of child and parental sleep and implementation of effective interventions may be a gateway to improve quality of survival in pediatric ALL.
Metabolomics of endemic sixAstragalusspecies by combined NMR and GC‐MS analysis
Authors: Sahin Yaglioglu Ayse , Temirturk Murat , Ugur Emic , Dolarslan Melda , Demirtas Ibrahim 
Published: January 2020

AbstractIntroductionAstragalus anthylloides,A. dipsaceus,A. karamasicus,A. lycius,A. sigmoideusand A. xylobasisvar.angustusare an endemic and generally grow in the Irano‐Turanian phytogeographic region of Turkey.Astragalusspecies contain saponins, polysaccharides, and phenolics, while the toxic compounds include imidazoline alkaloids, nitro toxins, and selenium derivatives.ObjectivesTo apply a combined metabolomic fingerprinting approach by nuclear magnetic resonance (NMR) and gas chromatography‐mass spectrometry (GC‐MS) of endemic sixAstragalusspecies extract.MethodologyThe whole plant collected in Turkey of six endemicAstragalussubsp. were dried and then extracted with hexane, chloroform, ethylacetate,n‐butanol and methanol solvents, respectively. The hexane extracts were analyzed by GC‐MS. Carbon‐13 (13C)‐NMR analyzes of all extracts were performed. In both analyses, a biomarker was obtained.ResultsThe hexane extracts were determined as palmitic acid, arachidic acid, behenic acid, and linolenic acid as the main components. As a result of13C‐NMR analyzes, in hexane, chloroform, and ethylacetate the extracts detected were palmitic acid, arachidic acid, behenic acid, and linolenic acid.d‐Pinitol was obtained using13C‐NMR analyzes withn‐butanol and methanol extracts.ConclusionThis study demonstrated thatd‐pinitol is a biomarker for the endemic sixAstragalussubsp.
From depressive symptoms to suicide risk: Roles of sense of belongingness and acquired capability for suicide in patients with mental disorders
Authors: Wang Shengnan , Li Congcong , Jia Xuji , Lyu Juncheng , Wang Yanyu , Sun Hongwei 
Published: January 2020

AbstractIn order to prevent suicides in patients with mental disorders, it was critical to recognize the risk factors and explore the mechanism. Based on depressive symptoms, which were common in patients with mental disorders in consolidation period in China, we constructed a moderated mediating model under the framework of Integrated Motivational‐Volitional Model of suicidal behaviour, and examined the mechanism of how depressive symptoms, thwarted belongingness, and acquired capability for suicide influenced suicide risk. In this study, data were collected from 164 patients through four questionnaires, and analyzed with PROCESS macro for SPSS (Hayes, 2008). The result showed that in the predictive effects of depressive symptoms on suicide risk, thwarted belongingness was a partial mediating variable, while acquired capability for suicide played a moderating role in the partial mediating model. Specifically, the predictive effects of depressive symptoms and thwarted belongingness, both as motivation variables, on suicide risk both occurred in the case of the high acquired capability of suicide, which was a volition variable. The research pointed out the interdependence of depressive symptoms and a sense of belongingness, and clarified the critical role of acquired capability for suicide. The integrated perspective could enhance the interpretation of reality, and enlightened those carrying out the practice of suicide intervention to patients with mental disorders.
Controllable synthesis of silica nanoparticle size and packing efficiency onto PVP‐functionalized PMMA via a sol–gel method
Authors: Kim Gi H. , Hwang Sung W. , Kang Dong H. , Jung Bich N. , Lee Mi J. , Shim Jin K. , Seo Kwan H. 
Published: January 2020

ABSTRACTThis study aimed to investigate synthesis and adsorption behavior of silica nanoparticles onto polyvinylpyrrolidone (PVP)‐functionalized poly(methyl methacrylate) under various conditions such as methanol/water ratio, ammonium hydroxide concentration, polymer contents, tetraethylorthosilicate contents, and total volume of solvent via sol–gel method. First, the copolymerization of methyl acrylate as a comonomer and 1‐dodecanethiol as a chain transfer agent increased the thermal stability of the product; however, the uniformity of the PMMA particles decreased because of the chain transfer reaction. Second, the adsorption behavior and size of silica nanoparticles could be controlled by adjusting the silica synthesis conditions. The adsorbed silica particle size was greatly influenced by the ammonium hydroxide concentration and the addition of water further enhanced the size increase. However, increasing the water content reduced the packing efficiency of the adsorbed silica particles. Increasing the PVP‐functionalized PMMA content at a fixed TEOS content linearly decreased the silica particle size. But TEOS concentration did not significantly affect the silica particle size. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 662–672
Transnational mobility desires and discourses: Young people from return‐migrant families negotiate intergenerationality, mobility capital, and place embeddedness
Authors: Ní Laoire Caitríona 
Published: January 2020

AbstractA longitudinal and intergenerational perspective opens up possibilities of novel insights into the socio‐spatial practices and relations that constitute, and generate, transnational youth im/mobilities. This paper draws on research conducted over 10 years with young adults who had migrated to Ireland as children with their return‐migrant parents during the Celtic Tiger period. It explores how, as young adults, they envisage and navigate their unfolding im/mobility pathways. In a context where transnational mobility experience is highly valued and celebrated, they draw on their mobility capital as former migrants to self‐position as knowledgeable mobile subjects. However, precisely because of their personal and family mobility resources, their engagements with discourses of hypermobility are selective—simultaneously claiming the cultural capital of transnational mobility and de‐fetishising it by producing grounded interpretations that value place embeddedness. The paper sheds light on some of the tensions of contemporary youth mobilities in contexts of globalisation, uncertainty, and migration.
Dynamic predictor for systems with state and input delay: A time‐domain robust stability analysis
Authors: Juárez Luis , Mondié Sabine , Kharitonov Vladimir L. 
Published: January 2020

SummaryThe robust stability of linear systems with both state and input delay in closed loop with dynamic predictor‐based controller is analyzed. The problem of time‐varying matrix uncertainty is studied in the Lyapunov‐Krasovskii framework. The complete type functional with prescribed derivative expressed in terms of the delay Lyapunov matrix associated with the nominal system is a key piece of our analysis. The robust stability conditions depend on the delay Lyapunov matrix whose computation is carried out. An illustrative example is presented.
Thiourea Derivatives Based on the Dapsone‐Naphthoquinone Hybrid as Anticancer and Antimicrobial Agents: In Vitro Screening and Molecular Docking Studies
Authors: Alimohammadi Aazam , Mostafavi Hossein , Mahdavi Majid 
Published: January 2020

AbstractAccording to the structure‐activity relationships (SAR), we synthesized a series of novel thiourea derivatives based on the dapsone‐naphthoquinone hybrid by the nucleophilic addition reaction of various primary/secondary amines to 2‐[4‐(4‐isothiocyanato‐benzenesulfonyl)‐phenylamino]‐[1,4]naphthoquinone (4). All thiourea derivatives (5 a‐j) were screened for in vitro anticancer activity against human leukemia cell line (K562). Thiourea derivative containing N‐methyl piperazine (5 h) was identified as the most effective molecule with IC50= 5.8±0.55 μM. Antimicrobial activity of thiourea derivatives (5 a–j) was evaluated in vitro against six strains of bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli, Salmonella enterica and Klebsiella pneumoniae) and a fungus Candida kefyr by the microdilution method. Interestingly, compound 5 h exhibited better antibacterial activity compared with the dapsone as a positive control against S. epidermidis. The molecular docking studies indicated that compound 5 h may act as anticancer agent through the inhibition of Abl kinase and T315I Abl mutant.
A Molecularly Imprinted Polymer Capped Nitrogen‐Doped Graphene Quantum Dots System for Sensitive Determination of Tetracycline in Animal‐Derived Food
Authors: Zhang Lei , Wang Junping , Fang Guozhen , Deng Jiankang , Wang Shuo 
Published: January 2020

AbstractA novel, highly sensitive and selective fluorescent sensor based on water‐soluble nitrogen‐doped graphene quantum dots (N‐GQDs) coupled with molecularly imprinted polymers (MIPs) was developed to detect tetracycline (TC). Unique N‐GQDs@MIPs nanomaterials were synthesized via the simple sol‐gel method due to its advantages of saving time and costs. The prepared N‐GQDs were fairly uniform and the fluorescence quantum yield (QY) was up to 58.2%. Results of transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) confirmed that the N‐GQDs@MIPs nanomaterial was prepared successfully. The imprinted factor (IF) of the synthesized N‐GQDs@MIPs was 3.42. Under the optimized experimental conditions, the fluorescence intensity and concentration of TC maintained a good linear range. The recovery experiment indicated this method can be applied to detecting TC in animal‐derived food. In summary, the proposed method provided a new and effective way for simple and rapid analysis of specific components in complex matrix samples.
Incorporation of risk preferences in a value‐based systems engineering framework
Authors: Kannan Hanumanthrao , Mesmer Bryan L. , Bloebaum Christina L. 
Published: January 2020

AbstractLarge‐scale complex engineered systems are designed in large organizations consisting of hundreds or thousands of individuals making design decisions at different stages in the process. These complex systems are inherently multidisciplinary and uncertain, involving diverse disciplines spanning geographical locations. Without a means to guide their decisions, these many decision‐makers fall back on selecting a design according to their own value and risk preferences. The primary focus of this paper is to enable consistency in design decision‐making with respect to both value and risk preferences of the stakeholder. A new value‐based systems engineering (VBSE) framework is presented that enables physics‐based system consistency as well as consistency in communication of value and risk preferences for design decision‐making in a hierarchically decomposed system. This framework embraces principles of value‐driven design and multidisciplinary design optimization, while also ensuring consistency in risk preferences throughout the system to address uncertainty. Improper communication of risk preferences could result in nonoptimal designs, which are risk biased by the design decision‐makers at different levels of the hierarchy, with respect to the stakeholder's preferences. Consistency in risk preferences in the context of the VBSE framework is addressed in this research by incorporating decision analysis techniques.
AdS4/CFT3 from weak to strong string coupling
Authors: Binder Damon J. , Chester Shai M. , Pufu Silviu S. 
Published: January 2020

Abstract
We consider the four-point function of operators in the stress tensor multiplet of the U(N)k× U(N)−k ABJM theory, in the limit where N is taken to infinity while N/k5 is held fixed. In this limit, ABJM theory is holographically dual to type IIA string theory on AdS4× ℂℙ3 at finite string coupling gs∼ (N/k5)1/4. While at leading order in 1/N, the stress tensor multiplet four-point function can be computed from type IIA supergravity, in this work we focus on the first subleading correction, which comes from tree level Witten diagrams with an R4 interaction vertex. Using superconformal Ward identities, bulk locality, and the mass deformed sphere free energy previously computed to all orders in 1/N from supersymmetric localization, we determine this R4 correction as a function of N/k5. Taking its flat space limit, we recover the known R4 contribution to the type IIA S-matrix and reproduce the fact that it only receives perturbative contributions in gs from genus zero and genus one string worldsheets. This is the first check of AdS/CFT at finite gs for local operators. Our result for the four-point correlator interpolates between the large N, large ’t Hooft coupling limit and the large N finite k limit. From the bulk perspective, this is an interpolation between type IIA string theory on AdS4× ℂℙ3 at small string coupling and M-theory on AdS4× S7/ℤk.