bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification of Type 2 Diabetes Genetic Variants and a Novel Genetic Risk Score Association With Insulin Clearance
Authors: Goodarzi Mark O , Palmer Nicholette D , Cui Jinrui , Guo Xiuqing , Chen Yii-Der I , Taylor Kent D , Raffel Leslie J , Wagenknecht Lynne E , Buchanan Thomas A , Hsueh Willa A , Rotter Jerome I 
Published: November 2019

Abstract

Context
Genome-wide association studies have identified more than 450 single nucleotide polymorphisms (SNPs) for type 2 diabetes (T2D).

Objective
To facilitate use of these SNPs in future genetic risk score (GRS)-based analyses, we aimed to classify the SNPs based on physiology. We also sought to validate GRS associations with insulin-related traits in deeply phenotyped Mexican Americans.

Design, Setting, and Participants
A total of 457 T2D SNPs from the literature were assigned physiologic function based on association studies and cluster analyses. All SNPs (All-GRS), beta-cell (BC-GRS), insulin resistance (IR-GRS), lipodystrophy (Lipo-GRS), and body mass index plus lipids (B + L–GRS) were evaluated for association with diabetes and indices of insulin secretion (from oral glucose tolerance test), insulin sensitivity and insulin clearance (from euglycemic clamp), and adiposity and lipid markers in 1587 Mexican Americans.

Results
Of the 457 SNPs, 52 were classified as BC, 30 as IR, 12 as Lipo, 12 as B + L, whereas physiologic function of 351 was undefined. All-GRS was strongly associated with T2D. Among nondiabetic Mexican Americans, BC-GRS was associated with reduced insulinogenic index, IR-GRS was associated with reduced insulin sensitivity, and Lipo-GRS was associated with reduced adiposity. B + L–GRS was associated with increased insulin clearance. The latter did not replicate in an independent cohort wherein insulin clearance was assessed by a different method.

Conclusions
Supporting their utility, BC-GRS, IR-GRS, and Lipo-GRS, based on SNPs discovered largely in Europeans, exhibited expected associations in Mexican Americans. The novel association of B + L–GRS with insulin clearance suggests that impaired ability to reduce insulin clearance in compensation for IR may play a role in the pathogenesis of T2D. Whether this applies to other ethnic groups remains to be determined.
Axo-glial interdependence in peripheral nerve development
Authors: Fledrich Robert , Kungl Theresa , Nave Klaus-Armin , Stassart Ruth M. 
Published: November 2019

ABSTRACT
During the development of the peripheral nervous system, axons and myelinating Schwann cells form a unique symbiotic unit, which is realized by a finely tuned network of molecular signals and reciprocal interactions. The importance of this complex interplay becomes evident after injury or in diseases in which aspects of axo-glial interaction are perturbed. This Review focuses on the specific interdependence of axons and Schwann cells in peripheral nerve development that enables axonal outgrowth, Schwann cell lineage progression, radial sorting and, finally, formation and maintenance of the myelin sheath.
Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature
Authors: Okuhara Shigeru , Birjandi Anahid A. , Adel Al-Lami Hadeel , Sagai Tomoko , Amano Takanori , Shiroishi Toshihiko , Xavier Guilherme M. , Liu Karen J. , Cobourne Martyn T. , Iseki Sachiko 
Published: November 2019

ABSTRACTThe tongue is a highly specialised muscular organ with a complex anatomy required for normal function. We have utilised multiple genetic approaches to investigate local temporospatial requirements for sonic hedgehog (SHH) signalling during tongue development. Mice lacking a Shh cis-enhancer, MFCS4 (ShhMFCS4/−), with reduced SHH in dorsal tongue epithelium have perturbed lingual septum tendon formation and disrupted intrinsic muscle patterning, with these defects reproduced following global Shh deletion from E10.5 in pCag-CreERTM; Shhflox/flox embryos. SHH responsiveness was diminished in local cranial neural crest cell (CNCC) populations in both mutants, with SHH targeting these cells through the primary cilium. CNCC-specific deletion of orofaciodigital syndrome 1 (Ofd1), which encodes a ciliary protein, in Wnt1-Cre; Ofdfl/Y mice led to a complete loss of normal myotube arrangement and hypoglossia. In contrast, mesoderm-specific deletion of Ofd1 in Mesp1-Cre; Ofdfl/Y embryos resulted in normal intrinsic muscle arrangement. Collectively, these findings suggest key temporospatial requirements for local SHH signalling in tongue development (specifically, lingual tendon differentiation and intrinsic muscle patterning through signalling to CNCCs) and provide further mechanistic insight into the tongue anomalies seen in patients with disrupted hedgehog signalling.
Dynamics of Spaetzle morphogen shuttling in the Drosophila embryo shapes gastrulation patterning
Authors: Rahimi Neta , Averbukh Inna , Carmon Shari , Schejter Eyal D. , Barkai Naama , Shilo Ben-Zion 
Published: November 2019

ABSTRACT
Establishment of morphogen gradients in the early Drosophila embryo is challenged by a diffusible extracellular milieu, and by rapid nuclear divisions that occur at the same time. To understand how a sharp gradient is formed within this dynamic environment, we followed the generation of graded nuclear Dorsal protein, the hallmark of pattern formation along the dorso-ventral axis, in live embryos. The dynamics indicate that a sharp extracellular gradient is formed through diffusion-based shuttling of the Spaetzle (Spz) morphogen that progresses through several nuclear divisions. Perturbed shuttling in wntD mutant embryos results in a flat activation peak and aberrant gastrulation. Re-entry of Dorsal into the nuclei at the final division cycle plays an instructive role, as the residence time of Dorsal in each nucleus is translated to the amount of zygotic transcript that will be produced, thereby guiding graded accumulation of specific zygotic transcripts that drive patterned gastrulation. We conclude that diffusion-based ligand shuttling, coupled with dynamic readout, establishes a refined pattern within the diffusible environment of early embryos.
Hmgcr promotes a long-range signal to attract Drosophila germ cells independently of Hedgehog
Authors: Kenwrick Kim , Mukherjee Amrita , Renault Andrew D. 
Published: November 2019

ABSTRACT
During development, many cell types migrate along stereotyped routes determined through deployment of cell surface or secreted guidance molecules. Although we know the identity of many of these molecules, the distances over which they natively operate can be difficult to determine. Here, we have quantified the range of an attractive signal for the migration of Drosophila germ cells. Their migration is guided by an attractive signal generated by the expression of genes in the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Hmgcr) pathway, and by a repulsive signal generated by the expression of Wunens. We demonstrate that the attractive signal downstream of Hmgcr is cell-contact independent and acts at long range, the extent of which depends on Hmgcr levels. This range would be sufficient to reach all of the germ cells for their entire migration. Furthermore, Hmgcr-mediated attraction does not require Wunens but can operate simultaneously with Wunen-mediated repulsion. Finally, several papers posit Hedgehog (Hh) as being the germ cell attractant downstream of Hmgcr. Here, we provide evidence that this is not the case.
Methods of stent placement in patients with upper-third and middle-third esophageal cancer
Authors: Kirkilevsky S. I. , Krahmalyov P. S. , Frydel R. I. , Dobrzhanskyi O. Y. 
Published: November 2019

Relevance. At that moment of diagnosis patients with esophageal cancer (EC) are often inoperable due to locally advanced disease. Life expectancy in such cases augmented with dysphagia comprises 90 days in average. Curative treatment can be performed only in 20-30 % of patients with a 5-year survival rate varying from 10,3 to 35%.Objective. Assessing short-term and long-term outcomes of patients with stents with EC depending on the localization of the primary tumor.Materials and methods. We analyzed our experience of using intraesophageal self-expanding stents in ЕС patients. 49 of patients them had tumor in upper-third of esophagus and 73 patients had middle-third esophageal tumor location as compared to those who underwent stoma formation (53 patients) in EC patients.Results. All patients who were stented had significantly lower grade of dysphagia and could eat in the ordinary way. It also improved quality of life, and many of such patients had an opportunity to continue treatment. It has been revealed that stenting of inoperable cancer patients with upper and middle-third esophageal cancer gives benefit to patients as it allows to continue to eat naturally and thereby significantly improves the quality of life in contrast to stoma placement. Patients with upper-third esophageal cancer who were not stented because of fistula formation had significantly better long-term survival than EC patients with stoma and similar cancer patients with middle-third esophageal tumors. Survival rate of patients with cancer of upper-third of esophagus after stenting not because of fistula was significantly better. Patients with cancer of the middle esophagus, who experienced stent placement because of fistulae, had the same long-term survival rate as cancer patients with middle esophageal tumors and with fistula who were not stented. It shows high efficacy of stenting in cancer of the middle-third esophagus with presence of fistula.Conclusion. Stent placement in case of inoperable cancer of upper and middle-third of esophagus shows significant benefit. It allows patients to eat in an ordinary was, and thereby significantly improves the quality of life in comparison with stoma formation.
Long-Duration Oral Vancomycin to Treat Clostridioides difficile in Patients With Inflammatory Bowel Disease Is Associated With a Low Rate of Recurrence
Authors: Lei Donald K. , Ollech Jacob E. , Andersen Michael , Weisshof Roni , Zmeter Nada , Sossenheimer Philip , Rubin David T. 
Published: November 2019

OBJECTIVES:
Patients with inflammatory bowel disease (IBD) are susceptible to Clostridioides difficile infections (CDIs), suffering from greater morbidity and mortality than the general population. Previous studies have proven the efficacy of oral vancomycin therapy in CDI, but there are no definitive guidelines to treat patients with IBD. We assessed the relationship between the length of vancomycin therapy and rates of CDI recurrence and reinfection in patients with IBD.

METHODS:
We compared rates of CDI recurrence and reinfection in Crohn's disease and ulcerative colitis (UC) patients receiving long-duration (LD) and short-duration (SD) oral vancomycin therapy, defined as 21–42 days and 10–14 days, respectively. Recurrence and reinfection were defined as positive C. difficile toxin assay by polymerase chain reaction within 8 weeks of the end of antibiotic therapy and after 8 weeks of the end of antibiotic therapy, respectively. The Fisher exact test was used to test for significance, and multivariate logistic regression models were constructed to control for other covariables.

RESULTS:
One hundred thirty-four patients with IBD (57 ulcerative colitis and 77 Crohn's disease) met inclusion criteria. LD vancomycin had a 1.8% incidence of CDI recurrence, compared with 11.7% in the SD vancomycin group (odds ratio = 0.13, P = 0.043). CDI reinfection rates and time to reinfection were not significantly different (LD 14.0% vs SD 16.9%, P = NS). Multivariate logistic regression models showed that treatment with LD vancomycin had lower odds for recurrence than SD vancomycin (odds ratio = 0.03, P = 0.021).

DISCUSSION:
LD vancomycin is associated with lower rates of CDI recurrence compared with SD vancomycin therapy. These results will help guide clinical decisions and the development of a prospective trial.
Электронное правительство vs цифровое правительство в контексте цифровой трансформации
Authors: Павлютенкова Марианна Юрьевна 
Published: November 2019

Работа затрагивает вопросы преобразования электронного правительства в цифровое в рамках процесса цифровизации, охватившего развитые страны мира. Цель исследования заключается в рассмотрении сущностей электронного правительства и цифрового правительства и разведении этих понятий. Ставится вопрос: является ли цифровое правительство лишь этапом развития электронного правительства или это масштабный проект, представляющий концептуальное развитие электронного правительства, но имеющий принципиальные отличия от него? Методология исследования включает исторический, аналитический методы, системный и сетевой подходы, социологические и статистические методы, эмпирические методы (рейтингование, включенное наблюдение).
В статье анализируются сущность и этапы становления и развития электронного и цифрового правительств. Изучение аналитических исследований, в частности десяти докладов ООН по развитию электронного правительства с 2001 по 2018 гг. и ряда других документов, позволило проследить эволюцию определений, понимания электронного правительства и направлений его развития, а также зафиксировать момент концептуального сдвига от электронного правительства к цифровому. Сформулированы базовые принципы и даны обобщенные характеристики цифрового правительства.
Сделаны выводы о том, что в концепции электронного правительства основное внимание было сосредоточено на предоставлении услуг в электронном виде. Цифровое правительство, являясь развитием электронного правительства, уникально отличается от него, будучи всеобъемлющей концепцией и обладая рядом специфических аспектов, которые должны стать ключевыми стратегическими элементами политики государства, осуществляющего цифровую трансформацию.
Цифровизация экономики России: тенденции, кадры, платформы, вызовы государству
Authors: Расторгуев Сергей Викторович , Тян Юлия Сергеевна 
Published: November 2019

Проанализирована взаимосвязь индекса глобальной конкурентоспособности российской экономики с различными цифровыми индексами на основе метода полигона распределения. На макроуровне с помощью статистических методов корреляционного и регрессионного анализа рассчитывается зависимость основных индикаторов цифровизации экономики и выявляются ключевые тренды. В рамках концепции К. Шваба «Индустрия 4.0», интерпретирующей взаимозависимость технологических, социальных, культурных, политических изменений, исследуется подготовка кадров для цифровой экономики в ведущих российских университетах. Делается вывод о необходимости введения в учебные планы дисциплин, отражающих запросы работодателей на цифровизацию бизнес-процессов. Через призму концепции изменения бизнес-процессов и трансформации цепочки создания стоимости анализируется отраслевой кейс «Яндекс.Такси». Показывается роль платформ, маркетплейсов, «больших данных» в создании сетевого эффекта.
Авторы делают вывод об эволюционном («ползучем») характере цифровизации в макроэкономике, социальной сфере современной России и возможности революционного («галопирующего») изменения отдельного сегмента рынка. Цифровые трансформации бизнес-процессов приводят к существенным изменениям модели пяти сил М. Портера. Такие классические концепты, как спрос, предложение, клиенты, поставщики, конкуренты, заимствуют друг у друга ряд существенных характеристик, что создает новую рыночную ситуацию. Авторы акцентируют внимание на том, что внешние неблагоприятные эффекты цифровизации должны решаться с помощью государства, бюджетной политики и правового регулирования.
«Много здесь, кто в стриме…» Распространение социальных медиа и девальвация основных средств массовой информации в Венгрии
Authors: Сирмаи Эва 
Published: November 2019

В Венгрии с 1989 г. идут горячие споры о статусе общественного телевидения и радио. Центральным вопросом этих дебатов является политическая принадлежность электронных СМИ и возможности появления оппозиции и гражданской сферы в общественных медиа. Оппозиционные партии (в парламенте и вне его), а также гражданские организации недостаточно представлены в основных средствах массовой информации, их позиции с большей вероятностью будут опосредованы через социальные сети, в первую очередь Facebook или тематические блоги.
В декабре 2018 г. в венгерском парламенте, несмотря на обструкцию оппозиции, был принят новый закон о труде (с тех пор известен как «Закон о рабстве»). Прошли демонстрации против закона, организованные оппозиционными партиями, профсоюзами и гражданскими организациями. Из-за отсутствия объективного и беспристрастного репортажа об этих событиях на каналах общественных средств массовой информации изменились темы требований, необходимость свободного и независимого информирования была объявлена ​​одним из основных. Прямые трансляции событий, произошедших перед зданием парламента и государственного телерадиовещателя, были почти исключительно доступны пользователям Facebook через стриминговое видео участников. Таким образом, сервис Facebook «прямой эфир» (потоковое видео в реальном времени через мобильные устройства) стал важнейшим источником информации и самым эффективным инструментом мобилизации. Этот сервис позволил лидерам общественного мнения связаться со своими последователями, а участникам — задокументировать акции полиции и насильственные действия. Интерактивность способствовала конфронтации мнений на платформе Facebook и стала способом политической активизации.
В статье рассматривается, как эти события представлены в личных профилях лидеров оппозиционных партий, как использование функции «прямой эфир» влияет на исход событий и как политические дискуссии в социальных сетях могут привести к беспрецедентному уровню активности гражданского общества. Анализируя комментарии самых популярных публикаций (используя программное обеспечение для качественного анализа MAXQDA), автор исследует, способны ли пропагандистские сообщения — как со стороны правящей партии, так и со стороны оппозиции — радикализировать читателей, создать образ врага или углубить конфронтацию.
Dynamic cerebral perfusion parameters and magnetic nanoparticle accumulation assessed by AC biosusceptometry
Authors: Próspero André Gonçalves , Soares Guilherme Augusto , Moretto Gustavo Morlin , Quini Caio C. , Bakuzis Andris Figueiroa , de Arruda Miranda José Ricardo 
Published: November 2019

Abstract
Cerebral blood flow (CBF) assessment is mainly performed by scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI). New approaches to assess the CBF through the passage of magnetic nanoparticles (MNPs) to blood-brain barrier (BBB) are convenient to help decrease the use of ionizing radiation and unleash the required MRI schedule in clinics. The development of nanomedicine and new biomedical devices, such as the magnetic particle imaging (MPI), enabled new approaches to study dynamic brain blood flow. In this paper, we employed MNPs and the alternating current biosusceptometry (ACB) to study the brain perfusion. We utilized the mannitol, before the MNPs, injection to modulate the BBB permeability and study its effects on the circulation time of the MNPs in the brain of rats. Also, we characterized a new ACB sensor to increase the systems’ applicability to study the MNPs’ accumulation, especially in the animals’ brain. Our data showed that the injection of mannitol increased the circulation time of MNPs in the brain. Also, the mannitol increased the accumulation of MNPs in the brain. This paper suggests the use of the ACB as a tool to study brain perfusion and accumulation of MNPs in studies of new nano agents focused on the brain diagnostics and treatment.
Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
Authors: Roelofsen-de Beer Roseri , Wielders Jos , Boursier Guilaine , Vodnik Tatjana , Vanstapel Florent , Huisman Willem , Vukasović Ines , Vaubourdolle Michel , Sönmez Çiğdem , Linko Solveig , Brugnoni Duilio , Kroupis Christos , Lohmander Maria , Šprongl Luděk , Bernabeu-Andreu Francisco , Meško Brguljan Pika , Thelen Marc 
Published: November 2019

Abstract
This paper reflects the opinion of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO). It aims to provide guidance for drawing up local/national documents about validation and verification of laboratory methods. We demonstrate how risk evaluation can be used to optimize laboratory policies to meet intended use requirements as well as requirements of standards. This is translated in a number of recommendations on how to introduce risk evaluation in various stages of the implementation of new methods ultimately covering the whole process cycle.
Intermediale Wechselwirkung von Text und Bild zur Stilisierung einer idealen Märchenerzählerin
Authors: Murayama Isamitsu 
Published: November 2019

Zusammenfassung
Das Frontispizbildnis der Dorothea Viehmann zu den Kinder- und Hausmärchen untermauert zusammen mit den wissenschaftlichen Texten der Brüder Grimm die Authentizität der mündlichen Märchen als ein kulturelles Gedächtnis. Anhand der drei Fassungen dieses Porträts ist auch eine enge Wechselwirkung zwischen der Grimm’schen Beschreibung der Erzählerin und ihrer Visualisierung durch Ludwig Emil Grimm festzustellen, in das auch physiognomische Betrachtungsweisen, orientalistische Stereotypisierungen und Trauerarbeit mit hineinspielen. Somit konstruieren und stabilisieren die Brüder Grimm eine ideale Erzählerin, und das Porträt selbst wird damit zum kulturellen Gedächtnis.
Fabrication, mechanical properties and failure mechanism of random and aligned nanofiber membrane with different parameters
Authors: Liu Su-dan , Li Dian-sen , Yang Ying , Jiang Lei 
Published: November 2019

AbstractPolyacrylonitrile (PAN) nanofiber membranes with different concentrations, rotary speeds and four kinds of aligned with fiber orientation of 0∘, 0∘/90∘, 0∘/90∘/+45∘and 0∘/90∘/+45∘/−45∘were prepared via electrospinning technique. The nanofiber membranes were morphologically characterized and mechanically tested. The results showed that nanofibers have uniform structure without any beads when the concentration increased 12wt%. The tensile strength and modulus of PAN nanofiber membranes increase with increasing the concentration. The orientation of nanofibers increases significantly with increasing rotary speed and fabricated nanofibers membrane has best orientation and tensile properties at 2500rpm. Moreover, the tensile properties can be affected greatly by the fiber structure and these decrease significantly with increasing the fiber orientation angle. The results also show that the nanofiber membranes exhibit obvious ductile fracture characteristics. Moreover, shear characteristics become more evident with increasing the concentration, and the failure mode changes from shear feature to flush fracture with increasing the rotary speed. In addition, the failure patterns vary with fiber structure and the main damage is in the form of interlayer delaminating, interface debonding, fibers tearing and breakage of the nanofibers.