bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline mutation landscape of multiple endocrine neoplasia type 1 using full gene next-generation sequencing
Authors: Carvalho Rafael A , Urtremari Betsaida , Jorge Alexander A L , Santana Lucas S , Quedas Elisangela P S , Sekiya Tomoko , Longuini Viviane C , Montenegro Fabio L M , Lerario Antonio M , Toledo Sergio P A , Marx Stephen J , Toledo Rodrigo A , Lourenço Delmar M 
Published: October 2018

Background
Loss-of-function germline MEN1 gene mutations account for 75–95% of patients with multiple endocrine neoplasia type 1 (MEN1). It has been postulated that mutations in non-coding regions of MEN1 might occur in some of the remaining patients; however, this hypothesis has not yet been fully investigated.

Objective
To sequence for the entire MEN1 including promoter, exons and introns in a large MEN1 cohort and determine the mutation profile.

Methods and patients
A target next-generation sequencing (tNGS) assay comprising 7.2 kb of the full MEN1 was developed to investigate germline mutations in 76 unrelated MEN1 probands (49 familial, 27 sporadic). tNGS results were validated by Sanger sequencing (SS), and multiplex ligation-dependent probe amplification (MLPA) assay was applied when no mutations were identifiable by both tNGS and SS.

Results
Germline MEN1 variants were verified in coding region and splicing sites of 57/76 patients (74%) by both tNGS and SS (100% reproducibility). Thirty-eight different pathogenic or likely pathogenic variants were identified, including 13 new and six recurrent variants. Three large deletions were detected by MLPA only. No mutation was detected in 16 patients. In untranslated, regulatory or in deep intronic MEN1 regions of the 76 MEN1 cases, no point or short indel pathogenic variants were found in untranslated, although 33 benign/likely benign and three new VUS variants were detected.

Conclusions
Our study documents that point or short indel mutations in non-coding regions of MEN1 are very rare events. Also, tNGS proved to be a highly effective technology for routine genetic MEN1 testing.
Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency
Authors: Moniez Sophie , Pienkowski Catherine , Lepage Benoit , Hamdi Safouane , Daudin Myriam , Oliver Isabelle , Jouret Béatrice , Cartault Audrey , Diene Gwenaelle , Verloes Alain , Cavé Hélène , Salles Jean-Pierre , Tauber Maithé , Yart Armelle , Edouard Thomas 
Published: October 2018

Context
Abnormalities in the hypothalamo–pituitary–gonadal axis have long been reported in Noonan syndrome (NS) males with only few data available in prepubertal children.

Objective
The aim of this study was to describe the gonadal function of NS males from childhood to adulthood.

Design
It is a retrospective chart review.

Patients and methods
A total of 37 males with a genetically confirmed diagnosis of NS were included. Clinical and genetic features, as well as serum hormone levels (LH, FSH, testosterone, anti-Müllerian hormone (AMH), and inhibin B) were analysed.

Results
Of the 37 patients, 16 (43%) children had entered puberty at a median age of 13.5 years (range: 11.4–15.0 years); age at pubertal onset was negatively correlated with BMI SDS (r = −0.541; P = 0.022). In pubertal boys, testosterone levels were normal suggesting a normal Leydig cell function. In contrast, NS patients had significant lower levels of AMH (mean SDS: −0.6 ± 1.1; P = 0.003) and inhibin B (mean SDS: −1.1 ± 1.2; P < 0.001) compared with the general population, suggesting a Sertoli cell dysfunction. Lower AMH and inhibin B levels were found in NS-PTPN11 patients, whereas these markers did not differ from healthy children in SOS1 patients. No difference was found between cryptorchid and non-cryptorchid patients for AMH and inhibin B levels (P = 0.43 and 0.62 respectively). Four NS-PTPN11 patients had a severe primary hypogonadism with azoospermia/cryptozoospermia.

Conclusions
NS males display Sertoli cell-specific primary testicular insufficiency, whereas Leydig cell function seems to be unaffected.
High prevalence of syndromic disorders in patients with non-isolated central precocious puberty
Authors: Wannes Selmen , Elmaleh-Bergès Monique , Simon Dominique , Zénaty Delphine , Martinerie Laetitia , Storey Caroline , Gelwane Georges , Paulsen Anne , Ecosse Emmanuel , De Roux Nicolas , Carel Jean Claude , Léger Juliane 
Published: October 2018

Objective
Non-idiopathic CPP is caused by acquired or congenital hypothalamic lesions visible on MRI or is associated with various complex genetic and/or syndromic disorders. This study investigated the different types and prevalence of non-isolated CPP phenotypes.

Design and Methods
This observational cohort study included all patients identified as having non-idiopathic CPP in the database of a single academic pediatric care center over a period of 11.5 years. Patients were classified on the basis of MRI findings for the CNS as having either hypothalamic lesions or complex syndromic phenotypes without structural lesions of the hypothalamus.

Results
In total, 63 consecutive children (42 girls and 21 boys) with non-isolated CPP were identified. Diverse diseases were detected, and the hypothalamic lesions visible on MRI (n = 28, 45% of cases) included hamartomas (n = 17; either isolated or with an associated syndromic phenotype), optic gliomas (n = 8; with or without neurofibromatosis type 1), malformations (n = 3) with interhypothalamic adhesions (n = 2; isolated or associated with syndromic CNS midline abnormalities, such as optic nerve hypoplasia, ectopic posterior pituitary) or arachnoid cysts (n = 1). The patients with non-structural hypothalamic lesions (n = 35, 55% of cases) had narcolepsy (n = 9), RASopathies (n = 4), encephalopathy or autism spectrum disorders with or without chromosomal abnormalities (n = 15) and other complex syndromic disorders (n = 7).

Conclusion
Our findings suggest that a large proportion (55%) of patients with non-isolated probable non-idiopathic CPP may have complex disorders without structural hypothalamic lesions on MRI. Future studies should explore the pathophysiological relevance of the mechanisms underlying CPP in these disorders.
Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY
Authors: Buchfelder Michael , van der Lely Aart-Jan , Biller Beverly M K , Webb Susan M , Brue Thierry , Strasburger Christian J , Ghigo Ezio , Camacho-Hubner Cecilia , Pan Kaijie , Lavenberg Joanne , Jönsson Peter , Hey-Hadavi Juliana H 
Published: October 2018

Objectives
ACROSTUDY is an international, non-interventional study of acromegaly patients treated with pegvisomant (PEGV), a growth hormone receptor antagonist and has been conducted since 2004 in 15 countries to study the long-term safety and efficacy of PEGV. This report comprises the second interim analysis of 2090 patients as of May 12, 2016.

Methods
Descriptive analyses of safety, pituitary imaging and outcomes on PEGV treatment up to 12 years were performed.

Results
Prior to starting PEGV, 96% of patients had reported surgery, radiation, medical therapy or any combinations of those. At start of PEGV, 89% of patients had IGFI levels above the upper limit of normal (ULN). The percentage of patients with normal IGFI levels increased from 53% at year 1 to 73% at year 10, and the average daily dose of PEGV increased from 12.8 mg (year 1) to 18.9 mg (year 10). A total of 4832 adverse events (AEs) were reported in 1137 patients (54.4%), of which 570 were considered treatment related in 337 patients (16.1%). Serious AEs were reported in 22% of patients, of which 2.3% were considered treatment related. Locally reported MRIs showed most patients (72.2%) had no change in tumor size relative to the prior scan; 16.8% had a decrease, 6.8% an increase and 4.3% both. In patients with normal liver tests at PEGV start, an ALT or AST elevation of >3× ULN at any time point during their follow-up was reported in 3%.

Conclusions
This second interim analysis confirms that long-term use of PEGV is an effective and safe treatment in patients with acromegaly.
Preventive Use of Ascorbic Acid For Atrial Fibrillation After Coronary Artery Bypass Graft Surgery
Authors: Mirmohammadsadeghi Mohsen , Mirmohammadsadeghi Amir , Mahmoudian Mahsa 
Published: October 2018

Background: Atrial fibrillation is one of the most frequent complications and a major risk of morbidity and mortality after cardiac surgery. Antioxidants such as vitamin C are used for prevention of this arrhythmia. Different results of studies have been reported, but most of them have shown efficiency of vitamin C in prophylaxis of postoperative AF. We tried to examine this efficacy with larger sample size.
Methods: Three hundred and fourteen on pump coronary artery bypass graft surgery alone. Patients were divided into two groups: The intervention group received vitamin C (N = 160) and the control group did not receive any (N = 154). Intervention group was administered two grams of vitamin C intravenously (IV) 24 hours preoperatively, 500 mg every 12 hours IV for 48 hours in ICU, and 500 mg every 12 hours PO for 48 hours in ward. Continuous monitoring in ICU and three times a day ECG was used for AF detection. The two groups were compared.
Results: The two groups were matched in terms of age, sex, LA size, ejection fraction, functional class, and TSH level. Of the patients, 244 were male. Mean age was 62 years (40-84 years) in both groups. M/F ratio was four in both groups. Functional class and ejection fraction were the same in both groups. There was no mean TSH level difference. AF occurrence in vitamin C group was 7.6 % and in control group was 7.8 %. There was no difference in ICU or hospital stay.
Conclusions: Prophylactic use of vitamin C does not further reduce postoperative atrial fibrillation in on pump CABG patients.
PIE-1 Translation in the Germline Lineage Contributes to PIE-1 Asymmetry in the EarlyCaenorhabditis elegansEmbryo
Authors: Gauvin Timothy J , Han Bingjie , Sun Michael J , Griffin Erik E 
Published: October 2018

AbstractIn the C. elegans embryo, the germline lineage is established through successive asymmetric cell divisions that each generate a somatic and a germline daughter cell. PIE-1 is an essential maternal factor that is enriched in embryonic germline cells and is required for germline specification. We estimated the absolute concentration of PIE-1::GFP in germline cells and find that PIE-1::GFP concentration increases by roughly 4.5 fold, from 92 nM to 424 nM, between the 1 and 4-cell stages. Previous studies have shown that the preferential inheritance of PIE-1 by germline daughter cells and the degradation of PIE-1 in somatic cells are important for PIE-1 enrichment in germline cells. In this study, we provide evidence that the preferential translation of maternal PIE-1::GFP transcripts in the germline also contributes to PIE-1::GFP enrichment. Through an RNAi screen, we identified Y14 and MAG-1 (Drosophila tsunagi and mago nashi) as regulators of embryonic PIE-1::GFP levels. We show that Y14 and MAG-1 do not regulate PIE-1 degradation, segregation or synthesis in the early embryo, but do regulate the concentration of maternally-deposited PIE-1::GFP. Taken together, or findings point to an important role for translational control in the regulation of PIE-1 levels in the germline lineage.
Medicaid Expenditures Among Children With Noncomplex Chronic Diseases
Authors: Bettenhausen Jessica L. , Richardson Troy E. , Shah Samir S. , Hall Matt , Andrews Annie L. , Neff John M. , Auger Katherine A. , Hoefgen Erik R. , Macy Michelle L. , Plencner Laura M. , Zima Bonnie T. 
Published: October 2018

BACKGROUND AND OBJECTIVES:
Expenditures for children with noncomplex chronic diseases (NC-CDs) are related to disease chronicity and resource use. The degree to which specific conditions contribute to high health care expenditures among children with NC-CDs is unknown. We sought to describe patient characteristics, expenditures, and use patterns of children with NC-CDs with the lowest (≤80th percentile), moderate (81–95th percentile), high (96–99th percentile), and the highest (≥99th percentile) expenditures.

METHODS:
In this retrospective cross-sectional study, we used the 2014 Truven Medicaid MarketScan Database for claims from 11 states. We included continuously enrolled children (age &lt;18 years) with NC-CDs (n = 1 563 233). We describe per member per year (PMPY) spending and use by each expenditure group for inpatient services, outpatient services, and the pharmacy for physical and mental health conditions. K-means clustering was used to identify expenditure types for the highest expenditure group.

RESULTS:
Medicaid PMPY spending ranged from $1466 (lowest expenditures) to $57 300 (highest expenditures; P &lt; .001); children in the highest expenditure group were diagnosed with a mental health condition twice as often (72.7% vs 34.1%). Cluster analysis was used to identify 3 distinct groups: 83% with high outpatient mental health expenditures (n = 13 033; median PMPY $18 814), 15% with high inpatient expenditures (n = 2386; median PMPY $92 950), and 1% with high pharmacy expenditures (n = 213; median $325 412). Mental health conditions accounted for half of the inpatient diagnoses in the cluster analysis.

CONCLUSIONS:
One percent of children with the highest expenditures accounted for 20% of Medicaid expenditures in children with NC-CDs; mental health conditions account for a large proportion of aggregate Medicaid spending in children with NC-CDs.
La sociología de Georg Simmel y el ‘capital social’: La confianza como fuerza socializadora
Authors: Ovares Sánchez Carolina 
Published: October 2018

ResumenLa sociología de Simmel constituye uno de los orígenes teóricos de la noción de ‘capital social’. Lo anterior se concluye al analizar su investigación social, a partir de las formas y contenidos de los procesos de interacción social y el papel de la confianza en la sociedad como fuerza socializadora. Concluimos que Simmel contribuye de manera significativa a la conceptualización de ‘capital social’. La necesidad de lazos informales y la confianza como garantía para el mantenimiento de una sociedad y sus instituciones sociales es una constante en la sociología, desde sus inicios como disciplina. En este artículo se analizará y mostrará la contribución de Georg Simmel a las tesis sobre el capital social, desde su conceptualización de la confianza, como una de las fuerzas que configuran a la sociedad, la cual es base para el capital social. Concepto que sigue siendo un punto de referencia clave en las ciencias sociales.Palabras claves: G. Simmel; Capital social; Sociología; Confianza; Teoría social. Georg Simmel's Sociology and ‘Social Capital’: Trust as a Socializing ForceAbstractSimmel´s sociology constitutes one of the theoretical roots of the notion of 'social capital'. That is inferred by analyzing his social inquiry, based on the forms and contents of social interaction processes and the role of trust, as a socializing force, in society. We concluded that his contribution to the sociological conceptualization of this notion is significant. The necessity of informal ties and trust, as a guarantee for the establishment and maintenance of society, has been a constant in sociology since its origins. This article will analyze Georg Simmel's contribution, to the basis for social capital, from his approach of trust as one of the forces that shape society. This concept remains a key reference in social science.Key Words: G. Simmel; Social capital; Sociology; Trust; Social theory. Acerca del proceso editorial y sus publicaciones la revista Reflexiones utiliza la licencia Creative Commons (CC BY-NC-ND 4.0)
Sentidos y usos del “mirar mal” como eje de conflicto entre estudiantes
Authors: Di Napoli Pablo Nahuel 
Published: October 2018

ResumenEn el presente artículo se indaga sobre las prácticas y sentidos que construyen los jóvenes en torno a sus miradas, especialmente a un tipo particular de mirada que constituye un eje constante de conflicto en el espacio escolar: el “mirar mal”. En la primera parte se recuperan los aportes teóricos del campo sociológico sobre el rostro y la mirada desde una perspectiva relacional. En la segunda parte se analizan los significados que los estudiantes de educación secundaria le atribuyen al “mirar mal” y qué tipo de prácticas se ligan a ella en el ámbito escolar. El corpus empírico se compone de sesenta entrevistas en profundidad realizadas con jóvenes de dos escuelas medias de gestión estatal de la provincia de Buenos Aires en Argentina. Concluimos que a través de la mirada se ponen en juego diferentes aristas de la individualidad juvenil que los agentes educativos debieran tomar en cuenta al actuar sobre la sociodinámica de los conflictos en el ámbito escolar.Palabras clave: Jóvenes; Rostro; Subjetividad; Cuerpo; Escuela, Sentidos Sense and uses of "bad looking" as an axis of conflict among students AbstractIn this article we look into the meanings that young people build behind the practices of ways of eye gazing, especially to a particular type of gaze that constitutes a constant conflict axis at school: the"bad eye"or "angry stare". In the first part of this article, we recover the theoretical contributions of the sociological field about face and eye gaze from a relational perspective. Secondly, we analyze the meanings that high school students confer to the "bad eye" stare and the type of practices linked to it at academic environments. The empirical corpus consists of sixty in-depth interviews to young from two state high schools in Buenos Aires, Argentina. We conclude that through the look come into play different aspects of youth individuality that educators should take into account when acting on sociodynamics of conflicts in schools.Key Words: Young people, Face, Subjetivity, Body, School, Meaning Acerca del proceso editorial y sus publicaciones la revista Reflexiones utiliza la licencia Creative Commons (CC BY-NC-ND 4.0)
ALMANYA’DAKİ TÜRK SİVİL TOPLUM KURULUŞLARININ BAZI İÇ ÇEVRE FAKTÖRLERİ AÇISINDAN GÖRÜNÜMÜ: BAVYERA EYALETİNDEKİ TÜRK DERNEKLERİ ARAŞTIRMASI
Authors: Kocagöz Elif 
Published: October 2018

Almanya’da
yaşayan Türk toplumu, 50 yılı aşan bir zaman içerisinde Almanya’nın neredeyse her
bölgesine yayılmış dernekler kurarak, aktif bir sivil toplum hayatı inşaa
etmiştir. Gerek Almanya’daki gerekse Türkiye’deki mevcut gündemler,
Almanya’daki Türk toplumunu ve derneklerini geçmiş dönemlere kıyasla çok daha
önemli bir pozisyona getirmiştir. Buna rağmen literatürde hem Almanya genelinde
hem de eyaletler bazında Türk derneklerinin profillerini detaylı bir şekilde ortaya
koyan herhangi bir saha araştırmasıyla karşılaşılmamaktadır. Bu
çalışmanın amacı, Almanya’nın Bavyera eyaletinde faaliyette bulunan Türk derneklerinin
görünümlerini bazı iç faktörler itibariyle ortaya koymaktır. Çalışmada, konunun
uzmanlarıyla mülakatlar ve dernek temsilcileriyle anket şeklinde kalitatif ve
kantitatif araştırma teknikleri kullanılmıştır. Ankete, kayıtlı üye sayıları
toplamı 13.049 ve çoğunluğu 2000 yılı öncesinde kurulmuş olan, yıl bazında
toplam 2447 faaliyet üreten 96 dernek katılmış olup, derneklerin yarısı bir
başka çatı kuruluşa üyedir. Araştırmaya katılan derneklerce en sık yapılan
faaliyetler olarak kurumlarla görüşmeler ve temsil faaliyetleri, üyelere
yönelik iç toplantılar, ve konferans, söyleşi, vb. etkinlikler ifade
edilmiştir. Bulgular incelendiğinde derneklerin iç yapılarında
iyileştirilmelerin gerektiği çeşitli alanlarla karşılaşılmıştır.
GELİŞMEKTE OLAN ÜLKELERDE SERMAYE YAPISI BELİRLEYİCİLERİ: HİYERARŞİK LİNEER MODEL YAKLAŞIMI
Authors: BİLGİN Rümeysa 
Published: October 2018

Bu çalışmada
gelişmekte olan ülkelerde sermaye yapısı belirleyicileri Hiyerarşik Lineer
Model (HLM) yaklaşımı kullanılarak analiz edilmiştir. Oluşturulan panel veri
seti ülke, sektör, firma ve zaman düzeylerinden oluşan hiyerarşik bir yapı
olarak düzenlenmiş ve kaldıraç oranındaki değişkenlik varyans bileşenleri
modeli ile incelenmiştir. Sonuçta gelişmekte olan ülkelerde kaldıraç oranındaki
değişkenliğin büyük kısmının firma ve zaman düzeylerinden kaynaklandığı gözlemlenmiştir.
Ülkeye ve firmaya özgü bir dizi faktörün sermaye yapısı üzerindeki doğrudan ve
dolaylı etkilerini incelemek için ise rassal sabit ve rassal eğim modelleri kullanılmıştır.
Gelişmekte olan ülkelerde, firmaya özgü faktörlerin halka açık firmaların
sermaye yapısı kararları üzerinde ülkeye özgü faktörlere kıyasla çok daha
önemli olduğu bulgulanmıştır. Ülkeye özgü faktörlerin ise sermaye yapısı
üzerindeki doğrudan etkilerinin yanında firmaya özgü sermaye yapısı
belirleyicileri üzerinden dolaylı etkilerinin de olduğu söylenebilir.
Liderazgo y toma de decisiones a través de la gestión ambiental para una microempresa del sector plástico (Estudio de caso)
Authors: Osío Ospino Roberto Carlos 
Published: October 2018

Los Sistemas de Gestión Ambiental o SGA en las organizaciones son utilizados como una estrategia para generar valor agregado a las actividades y procesos para producción de un bien o un servicio. El sistema de gestión ambiental es una herramienta que busca proteger al medio ambiente y mitigar el impacto de los efectos generados por el crecimiento económico que hoy en día viven los países desarrollados y las economía emergentes. El siguiente trabajo es un estudio de caso del diseño de un SGA aplicado a una microempresa en la ciudad de Barranquilla (Colombia), dedicada a producir y comercializar artículos de plásticos para aseo de uso residencial e industrial de alta calidad para satisfacer las necesidades de almacenes de cadenas a nivel local y nacional e internacional; donde se mostrará el tipo de liderazgo necesario para alcanzar las metas del SGA propuesto por dicha organización.
Sistema de gestión de marketing estratégico para la empresa ETERNIT, en la ciudad de Barranquilla
Authors: Camargo Mejía Maryuris Rosa , Lozada Carbonell Rocío , Santamaría Constante Brian de J. 
Published: October 2018

El presente artículo es producto de una investigación de la productividad y competitividad de la empresa Eternit, perteneciente al sector de la construcción ubicada en la ciudad de Barranquilla, cuyo propósito es proponer un modelo de sistema en gestión de marketing estratégico que pueda ser implementado en esta empresa.
Para esto, se llevó a cabo una investigación de tipo analítico-inductivo, enmarcado en un paradigma cuantitativo, ya que la propuesta buscó las causas que obstaculizan la optimización de los recursos buscados por la logística y la consecución del pensamiento estratégico, por lo que obligó a realizar: un diagnóstico de la situación actual de esta empresa en referencia a su modelo de gestión; se hizo una evaluación de los modelos existentes y se escogieron los elementos más pertinentes que sirvieron en la construcción de un sistema de gestión de marketing estratégico que optimizará la toma de decisiones de la alta dirección a su interior.
La investigación sobre trayectorias académicas y experiencias de estudiantes en la educación superior intercultural en México
Authors: Bermúdez Flor Marina 
Published: October 2018

Este artículo presenta los resultados de un estado del conocimiento de la investigación sobre trayectorias académicas y experiencias escolares de jóvenes que participan de la educación superior intercultural en México. Se trata de textos publicados principalmente en español entre 2002 y 2015 (Se toma como punto de arranque en la revisión el texto de Carnoy et al. (2002) por ser el primero en abordar la profesionalización de indígenas en México en varios ámbitos de la actividad profesional y por aportar una lectura en el contexto profesionalizante del sureste de México). El estado de conocimiento comprende una revisión descriptiva y analítica de la bibliografía académica publicada en textos impresos y electrónicos que hacen referencia a las trayectorias o experiencias escolares de estudiantes indígenas y no indígenas. Se analiza quiénes son los sujetos de indagación, las metodologías, los marcos teóricos, las disciplinas y las áreas temáticas donde se inscriben los estudios. Además, se realiza un balance sobre el desarrollo de esta línea de investigación y se concluye sobre sus aportes disciplinares y de contenido. Por último, se proponen algunos ejes para su futuro desarrollo.