bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain
Authors: Furuse Tamio , Mizuma Hiroshi , Hirose Yuuki , Kushida Tomoko , Yamada Ikuko , Miura Ikuo , Masuya Hiroshi , Funato Hiromasa , Yanagisawa Masashi , Onoe Hirotaka , Wakana Shigeharu 
Published: August 2019

ABSTRACT
Dysfunction of glucose transporter 1 (GLUT1) proteins causes infantile epilepsy, which is designated as a GLUT1 deficiency syndrome (GLUT1DS; OMIM #606777). Patients with GLUT1DS display varied clinical phenotypes, such as infantile seizures, ataxia, severe mental retardation with learning disabilities, delayed development, hypoglycorrhachia, and other varied symptoms. Glut1Rgsc200 mutant mice mutagenized with N-ethyl-N-nitrosourea (ENU) carry a missense mutation in the Glut1 gene that results in amino acid substitution at the 324th residue of the GLUT1 protein. In this study, these mutants exhibited various phenotypes, including embryonic lethality of homozygotes, a decreased cerebrospinal-fluid glucose value, deficits in contextual learning, a reduction in body size, seizure-like behavior and abnormal electroencephalogram (EEG) patterns. During EEG recording, the abnormality occurred spontaneously, whereas the seizure-like phenotypes were not observed at the same time. In sleep-wake analysis using EEG recording, heterozygotes exhibited a longer duration of wake times and shorter duration of non-rapid eye movement (NREM) sleep time. The shortened period of NREM sleep and prolonged duration of the wake period may resemble the sleep disturbances commonly observed in patients with GLUT1DS and other epilepsy disorders. Interestingly, an in vivo kinetic analysis of glucose utilization by positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose imaging revealed that glucose transportation was reduced, whereas hexokinase activity and glucose metabolism were enhanced. These results indicate that a Glut1Rgsc200 mutant is a useful tool for elucidating the molecular mechanisms of GLUT1DS.
This article has an associated First Person interview with the joint first authors of the paper.
Therapeutic targeting of Notch signaling and immune checkpoint blockade in a spontaneous, genetically heterogeneous mouse model of T-cell acute lymphoblastic leukemia
Authors: Gao Jie , Van Meter Michael , Hernandez Lopez Susana , Chen Guoying , Huang Ying , Ren Shumei , Zhao Qi , Rojas Jose , Gurer Cagan , Thurston Gavin , Kuhnert Frank 
Published: August 2019

ABSTRACT
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer derived from the malignant transformation of T-cell progenitors. Outcomes remain poor for T-ALL patients who have either primary resistance to standard-of-care chemotherapy or disease relapse. Notably, there are currently no targeted therapies available in T-ALL. This lack of next-generation therapies highlights the need for relevant preclinical disease modeling to identify and validate new targets and treatment approaches. Here, we adapted a spontaneously arising, genetically heterogeneous, thymic transplantation-based murine model of T-ALL, recapitulating key histopathological and genetic features of the human disease, to the preclinical testing of targeted and immune-directed therapies. Genetic engineering of the murine Notch1 locus aligned the spectrum of Notch1 mutations in the mouse model to that of human T-ALL and confirmed aberrant, recombination-activating gene (RAG)-mediated 5′ Notch1 recombination events as the preferred pathway in murine T-ALL development. Testing of Notch1-targeting therapeutic antibodies demonstrated T-ALL sensitivity to different classes of Notch1 blockers based on Notch1 mutational status. In contrast, genetic ablation of Notch3 did not impact T-ALL development. The T-ALL model was further applied to the testing of immunotherapeutic agents in fully immunocompetent, syngeneic mice. In line with recent clinical experience in T-cell malignancies, programmed cell death 1 (PD-1) blockade alone lacked anti-tumor activity against murine T-ALL tumors. Overall, the unique features of the spontaneous T-ALL model coupled with genetic manipulations and the application to therapeutic testing in immunocompetent backgrounds will be of great utility for the preclinical evaluation of novel therapies against T-ALL.
Can Creatine Combat the Mental Fatigue–associated Decrease in Visuomotor Skills?
Authors: VAN CUTSEM JEROEN , ROELANDS BART , PLUYM BERT , TASSIGNON BRUNO , VERSCHUEREN JO , DE PAUW KEVIN , MEEUSEN ROMAIN 
Published: August 2019

ABSTRACT

Purpose
The importance of the brain in sports was recently confirmed by the negative effect of mental fatigue (MF) on sport-specific psychomotor skills. Creatine supplementation improves strength but can also improve cognitive functioning. To explore the role of creatine in combating MF, we evaluated whether creatine supplementation counteracts the MF-associated impairment in sport-specific psychomotor skills.

Methods
In 23°C, 14 healthy participants (4 females, 10 males; mean ± SD, age = 24 ± 3 yr, mass = 74 ± 13 kg, height = 179 ± 9 cm) performed a 90-min mentally fatiguing task (counterbalanced, crossover, and double-blinded; i.e., Stroop task) in two different conditions: after a 7-d creatine supplementation (CR; 20 g·d−1) and after a 7-d calcium lactate supplementation (placebo [PLAC]), separated by a 5-wk washout. In both conditions, a 7-min sport-specific visuomotor task, a dynamic handgrip strength endurance task, and a 3-min Flanker task was performed before and after the mentally fatiguing task. Physiological and perceptual responses were measured throughout the protocol.

Results
Handgrip strength endurance was higher in CR compared with PLAC (P = 0.022). MF impaired visuomotor response time (+4.4%; P = 0.022) and Flanker accuracy (−5.0%; P = 0.009) in both conditions. Accuracy on the Stroop task was higher in CR compared with PLAC (+4.9%; P = 0.026). Within the perceptual and physiological parameters, only motivation and vigor (P ≤ 0.027) were lower in CR compared with PLAC.

Conclusion
Creatine supplementation improved physical (strength endurance) and prolonged cognitive (Stroop accuracy) performance, yet it did not combat MF-induced impairments in short sport-specific psychomotor or cognitive (Flanker) performance. These results warrant further investigation in the potential role of creatine in combating the MF-associated decrements in prolonged (e.g., 90-min soccer game) sport performance and suggest a role of brain phosphocreatine in MF.
Os acromiale: a review of its incidence, pathophysiology, and clinical management
Authors: Hurst Simon A. , Gregory Thomas M. , Reilly Peter 
Published: August 2019

An os acromiale occurs when any of the primary ossification centres of the acromion fail to fuse with the basi-acromion. It is present in approximately 8% of individuals, and whilst the majority of these individuals are unaffected it can cause significant pain and disability. It can impact seemingly unrelated surgical intervention in the region such as subacromial decompression and reverse shoulder arthroplasty. A painful os acromiale can be both a diagnostic challenge, and difficult to manage. There remain a wide variety of surgical practices with variable outcomes achieved. We present an evidence-based discussion of the surgical techniques described to date in the literature, alongside a comprehensive review of the incidence and pathophysiology of os acromiale. This review was written after a comprehensive analysis of the literature to date relating to os acromiale. Particular focus was given to material examining surgical management techniques, and the condition’s incidence across different population groups. Open reduction and internal fixation using cannulated screws, or tension band wiring have superior outcomes in the literature in the treatment of symptomatic os acromiale. There may be a biomechanical advantage of combining the two techniques. Preservation of large anterior deltoid attachment is necessary, with consideration being given to the local blood supply. There is likely no additional benefit from iliac crest vs local bone grafting. Research in this area remains of a low evidence level with small samples sizes. Appropriately powered clinical research of a higher-level evidence methodology is needed in order to differentiate further in the choice of surgical intervention. Cite this article: EFORT Open Rev 2019;4:525-532. DOI: 10.1302/2058-5241.4.180100
Poor diagnostic values of stool analysis and steatocrit test in detecting exocrine pancreatic insufficiency
Authors: Widodo Ariani Dewi , Timan Ina Susianti , Bardosono Saptawati , Siagian Minarma , Winarta Widdy , Prasetyo Dwi , Firmansyah Agus 
Published: August 2019

BACKGROUND Exocrine pancreatic insufficiency (EPI) is one of the most challenging cases to be diagnosed accurately in Indonesia because of the unavailability of the fecal elastase-1 (FE-1) test, which is the primary indirect diagnostic tool till date. Stool analysis and steatocrit test are feasible alternatives as they can detect nutrient malabsorption, a consistent feature in EPI. Despite the common practice of using both tests, no study has ever been conducted in Indonesia to evaluate their accuracy.
METHODS This cross-sectional diagnostic study was conducted in 182 children aged 6–60 months. Study subjects were divided into children with persistent diarrhea (PD), those with malnutrition, and healthy children. Children with PD and malnutrition were selected on the basis of clinical criteria and the WHO z-score. FE-1 test was used as the gold standard to detect EPI. Primary endpoints of this study were sensitivity and specificity of the stool analysis and the steatocrit test. The accuracy of both tests, represented by area under the curve (AUC) values, was also evaluated individually and in combination.
RESULTS Each component of stool analysis and steatocrit test in each subgroup of patients generally had higher specificity than sensitivity. The specificity of both tests among healthy and malnourished children was good (≥70%), but among children with PD, the specificity of some components was <70%. The individual and combined AUC values of both tests in each subgroup of subjects were poor (<0.7).
CONCLUSIONS Stool analysis and steatocrit test cannot be used as alternative methods for FE-1 to detect EPI.
Phonological constraints on morphology: Evidence from Old English nominal inflection
Authors: Adamczyk Elżbieta , Versloot Arjen P. 
Published: August 2019

AbstractStudying the complex interaction between phonological and morphological developments involved in the extensive reorganisation of nominal inflection in early English, we focus, primarily, on new inflectional endings that emerged by analogy in etymologically suffix-less paradigm forms ofr-stems and root nouns. We argue that the analogical changes were essentially reactive to phonological developments, and to a large extent predictable in statistical terms. Investigating correlations in corpus data, we identify the factors that affected the probability that new analogical endings were adopted. The predictors of the directions of analogical change that we show to be robust include the syllable structure of the root, the salience of inherited and analogical inflectional markers, as well as their absolute and relative frequencies.
Alterations in rat adipose tissue transcriptome and proteome in response to prolonged fasting
Authors: Ibrahim Marianne , Ayoub Daniel , Wasselin Thierry , Van Dorsselaer Alain , Le Maho Yvon , Raclot Thierry , Bertile Fabrice 
Published: August 2019

Abstract
Various pathophysiological situations of negative energy balance involve the intense depletion of the body’s energy reserves. White adipose tissue is a central place to store energy and a major endocrine organ. As a model of choice to better understand how the white adipose tissue dynamically responds to changes in substrate availability, we used the prolonged fasting paradigm, which is characterized by successive periods of stimulated (phase 2) and then reduced (phase 3) lipid mobilization/utilization. Using omics analyses, we report a regulatory transcriptional program in rat epididymal (EPI) adipose tissue favoring lipolysis during phase 2 and repressing it during phase 3. Changes in gene expression levels of lipases, lipid droplet-associated factors, and the proteins involved in cAMP-dependent and cAMP-independent regulation of lipolysis are highlighted. The mRNA and circulating levels of adipose-secreted factors were consistent with the repression of insulin signaling during prolonged fasting. Other molecular responses are discussed, including the regulation of leptin and adiponectin levels, the specific changes reflecting an increased fibrinolysis and a possible protein catabolism-related energy saving mechanism in late fasting. Finally, some differences between internal and subcutaneous (SC) adipose tissues are also reported. These data provide a comprehensive molecular basis of adipose tissue responses when facing a major energetic challenge.
Necessity for redesigning premarital counseling classes based on marriage readiness from the perspective of adolescents and specialists: a need assessment based on the Bourich model and quadrant analysis
Authors: Satari Elahe , Akbari Kamrani Mahnaz , Farid Maliheh 
Published: August 2019

Abstract

Background and aim
The marriage readiness is a new concept that helps adolescents learn how to choose the right choices and have a better marital life. The present study aims to assess needs of the training priorities of marriage readiness using Bourich model and quadrant analysis.

Methods
The present study was a descriptive study. The research sample consisted of 400 students who participated in this study by random and convenience sampling from the three selected universities in the province of Alborz and 28 specialist and counselors in the sphere of marriage. The questionnaire of marriage readiness with 68 items has been provided in three areas including individual, interpersonal and contextual skills.

Results
The average age of student was 21.05 years. In the individual field, 20 training needs had priority scores more than 4 and the highest priority for youth in this area was “Lack of sexual inappropriate behaviors and habits and lack of disabling diseases.” In the area of interpersonal skills, the highest priority is related to “participation in pre-marital training, the ability to regulate the cost of living and the parenting ability “. In the field of contextual skills, 10 issues of training scored the priority scores of more than 4, and the highest priority was given to “having a vehicle, having sufficient income and financial independence.”

Conclusions
Based on the quadrant analysis model, the views of students and marriage counselors are not aligned and experts do not have the right viewpoints about the youth needs.
Back to the future: the proper name for red-backed voles is Clethrionomys Tilesius and not Myodes Pallas
Authors: Kryštufek Boris , Tesakov Alexey S. , Lebedev Vladimir S. , Bannikova Anna A. , Abramson Nataliya I. , Shenbrot Georgy 
Published: August 2019

Abstract
Two names (Clethrionomys and Myodes) are used interchangeably for red-backed voles, which is contrary to one of the fundamental principles of zoological nomenclature, that each taxon has a single and unique valid name. Fixation of Mus lemmus Linnaeus, 1758, as the type of Myodes Pallas, 1811, meets the requirements stipulated in the Article 69.1.1 of the 4th edition of the International Code of Zoological Nomenclature, and is therefore valid. Hence, the genus group name Myodes is a junior synonym of Lemmus Link, 1795, and is not available for red-backed voles. The oldest valid name for red-backed voles is Clethrionomys Tilesius, 1850, with the type species (Mus rutilus Pallas, 1779) subsequently designated by Palmer (1928).
Characterization of neat and modified asphalt binders and mixtures in relation to permanent deformation
Authors: Bessa Iuri S. , Takahashi Márcia M. , Vasconcelos Kamilla L. , Bernucci Liedi L. B. 
Published: August 2019

Abstract
The addition of polymers on asphalt binders aims to enhance their performance, especially at high temperatures, which correspond to rutting resistance. The Superpave rutting parameter (|G*|/sinδ) has been considered to be inadequate to characterize the performance of modified materials, therefore the Multiple Stress Creep and Recovery (MSCR) test was developed, providing the parameter non-recoverable compliance (Jnr). This research has the main objective of correlating asphalt binders performance-based characterization with rutting resistance of asphalt mixtures, and presents results obtained for one conventional (50/70 penetration grade) and two modified asphalt binders (2.1% RET and 1.9% RET) regarding their rheological characteristics. With the use of the dynamic shear rheometer (DSR), master curves and MSCR results were obtained for the three binders. In addition, permanent deformation tests were performed on the asphalt mixtures by means of laboratory traffic simulation. The rutting characterization indicated higher permanent deformation resistance for the modified binders for the asphalt binder and the asphalt mixture testing. The main conclusions were that the use of modified binder reduced in approximately 50% the Jnr values and the rut depth; also, the asphalt binders’ characteristics were able to predict the asphalt mixtures rutting resistance.
The Unique Structure of Pushkin’sEugene Onegin: Why Tatyana’s Identity and the Theme of Russianness Matters
Authors: Kim Sang Hyun 
Published: August 2019

SummaryPushkin’s novel in verseEugene Onegin(1833) has been considered not just the work of the period of Pushkin’s best and greatest lyrical output, but the starting-point of the classic nineteenth-century Russian novel. As this article strongly insists, the novel evokes the so-called ‘Russianness,’ which reminds us of what has typically been known as Russian or the Russian soul, as well as Russian types of emotional response reflected in the literary figure. The most important question this article addresses is the idea of Russianness encoded into the heroine, Tatyana, in particular. More concretely speaking, it is our main concern to investigate Tatyana’s identity as expressed through the motif of the Russian soul and its relationship with the structural uniqueness of the novel. The purpose of the present study then is to explore the extent to which this structural peculiarity is found throughout the text as well as how this question is associated with the characterization of the heroine, Tatyana. Fundamentally, the relationship between the text’s structural peculiarity and the character’s identity, in terms of thematic composition, will be at the center of our arguments.
Zur medialen Integration russlanddeutscher (Spät-)Aussiedler nach dem Fall Lisa und ihrer Mediendarstellung bis zur Bundestagswahl 2017
Authors: Schmalz Tatjana 
Published: August 2019

Summary
The majority of German Russians, who had settled in Germany in the 1990 s, were long considered conformist up to January 2016 where Russian media services and officials exploited the criminal case of Lisa F. in Berlin. A few right wing AfD party activists gathered several thousand Russian speakers to protest against the German refugee policy. Even though the activist’s mobilizing narrative can easily be deconstructed as a political myth with little consensus within the German Russian population, German mass media have since generalized this heterogeneous group as troublemakers with divided loyalties and as a potential threat to the federal elections of 2017. Although German Russian lobby organisations heavily criticised these mass media representations, they are likely to stand the chance of finally establishing their migration history as a part of general knowledge.
Nonlinear interest rate-setting behaviour of German commercial banks
Authors: Heinzelmann Ludwig , Missong Martin 
Published: August 2019

AbstractWe quantitatively analyse the interest rate-setting behaviour of German commercial banks during the period 2003–2014, using nonlinear (smooth transition) cointegration approaches. Our empirical results reveal principles applied by commercial banks in (re-)gaining margins in the aftermath of the financial crisis. We substantiate our findings using economic arguments from a bank management perspective. As our study contributes to a better understanding of the pass-through mechanism from market to commercial banks’ customer interest rates, the results will also be relevant to meaningful assessments of the effectiveness of monetary policy measures.
MiR-1906 attenuates neuropathic pain in rats by regulating the TLR4/mTOR/ Akt signaling pathway
Authors: Fang Xianhai , Zhou Huacheng , Huang Shaopeng , Liu Jinfeng 
Published: August 2019

Abstract

Background
This study determined the role of miR-1906 in neuropathic pain and proliferation in neuronal cells using a chronic constriction injury (CCI)-induced neuropathic pain (NP) rat model.

Methodology
NP was induced by CCI. Animals were divided into a sham group, an NP group, and a miR-1906 mimic group, which received 500 nmol/kg of a miR-1906 mimic intrathecally for 10 consecutive days following surgery. The effect of miR-1906 agomir was determined by estimating the thermal and mechanical withdrawal latency; an enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proinflammatory mediators. Western blotting and reverse-transcription polymerase chain reaction (RT-PCR) were used to determine protein expression in the spinal tissues of the CCI-induced neuropathic pain rat model.

Results
Administration of miR-1906 agomir increased the mechanical and thermal withdrawal latency period and the levels of inflammatory mediators compared with the NP group. Western blotting showed that treatment with miR-1906 agomir attenuated the levels of Akt, mTOR, TLR-4, and PI3K proteins in the spinal tissues of the CCI-induced neuropathic pain model. TLR-4 and NF-κB gene expression was lower in the miR-1906 agomir group than in the NP group.

Conclusion
miR-1906 gene stimulation reduced neuropathic pain by enhancing Akt/nTOR/PI3K and TLR-4/NF-κB pathway regulation.