bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Tumor DNA Profiling of Advanced Biliary Tract Cancers
Authors: Mody Kabir , Kasi Pashtoon M. , Yang JuDong , Surapaneni Phani Keerthi , Bekaii-Saab Tanios , Ahn Daniel H. , Mahipal Amit , Sonbol Mohamad B. , Starr Jason S. , Roberts Ali , Nagy Rebecca , Lanman Richard , Borad Mitesh J. 
Published: March 2019

PURPOSE Recent advances in molecular diagnostic technologies have allowed for the evaluation of solid tumor malignancies via noninvasive blood sampling, including circulating tumor DNA (ctDNA) profiling. We sought to characterize the ctDNA genomic alteration landscape in patients with biliary tract cancers (BTCs). PATIENTS AND METHODS From January 2015 to February 2018, 124 patients with BTC at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples (n = 122) were tested using the 73-gene panel that includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. RESULTS A total of 138 samples were included, with approximately 70% of patients having intrahepatic BTC. All patients had locally advanced or metastatic BTC. Samples with one or more alterations, when variants of unknown significance were excluded, numbered 105 (76%). Each sample contained, on average, three alterations with a median allelic fraction of 0.52%. The overall landscape of alterations is summarized in Figures 1 and 2. After excluding variants of unknown significance, therapeutically relevant alterations were observed in 76 patients (55%), including BRAF mutations, ERBB2 amplifications, FGFR2 fusions, FGFR2 mutations, and IDH1 mutations seen in 21% of patients. A different spectrum of alterations was observed in patients with early-onset BTC (younger than age 50 years) compared with older patients (older than age 50 years). CONCLUSION Data on ctDNA in BTC is currently limited. Our study, the largest cohort reported to date to our knowledge, demonstrates the feasibility of ctDNA testing in this disease. We provide a foundation upon which the field can continue to grow.
CryoAPEX – an electron tomography tool for subcellular localization of membrane proteins
Authors: Sengupta Ranjan , Poderycki Michael J. , Mattoo Seema 
Published: March 2019

ABSTRACT
We describe a method, termed cryoAPEX, which couples chemical fixation and high-pressure freezing of cells with peroxidase tagging (APEX) to allow precise localization of membrane proteins in the context of a well-preserved subcellular membrane architecture. Further, cryoAPEX is compatible with electron tomography. As an example, we apply cryoAPEX to obtain a high-resolution three-dimensional contextual map of the human FIC (filamentation induced by cAMP) protein, HYPE (also known as FICD). HYPE is a single-pass membrane protein that localizes to the endoplasmic reticulum (ER) lumen and regulates the unfolded protein response. Alternate cellular locations for HYPE have been suggested. CryoAPEX analysis shows that, under normal and/or resting conditions, HYPE localizes robustly within the subdomains of the ER and is not detected in the secretory pathway or other organelles. CryoAPEX is broadly applicable for assessing both lumenal and cytosol-facing membrane proteins.
Environmental temperature alters the overall digestive energetics and differentially affects dietary protein and lipid use in a lizard
Authors: Plasman Melissa , McCue Marshall D. , Reynoso Víctor Hugo , Terblanche John S. , Clusella-Trullas Susana 
Published: March 2019

ABSTRACTProcessing food (e.g. ingestion, digestion, assimilation) requires energy referred to as specific dynamic action (SDA) and is at least partially fuelled by oxidation of the nutrients (e.g. proteins and lipids) within the recently ingested meal. In ectotherms, environmental temperature can affect the magnitude and/or duration of the SDA, but is likely to also alter the mixture of nutrients that are oxidized to cover these costs. Here, we examined metabolic rate, gut passage time, assimilation efficiency and fuel use in the lizard Agama atra digesting cricket meals at three ecologically relevant temperatures (20, 25 and 32°C). Crickets were isotopically enriched with 13C-leucine or 13C-palmitic-acid tracers to distinguish between protein and lipid oxidation, respectively. Our results show that higher temperatures increased the magnitude of the SDA peak (by 318% between 32 and 20°C) and gut passage rate (63%), and decreased the duration of the SDA response (by 20% for males and 48% for females). Peak rate of dietary protein oxidation occurred sooner than peak lipid oxidation at all temperatures (70, 60 and 31 h earlier for 20, 25 and 32°C, respectively). Assimilation efficiency of proteins, but not lipids, was positively related to temperature. Interestingly, the SDA response exhibited a notable circadian rhythm. These results show that temperature has a pronounced effect on digestive energetics in A. atra, and that this effect differs between nutrient classes. Variation in environmental temperatures may thus alter the energy budget and nutrient reserves of these animals.
Functional specialization in the middle temporal area for smooth pursuit initiation
Authors: Bakhtiari Shahab , Pack Christopher C. 
Published: March 2019

Smooth pursuit eye movements have frequently been used to model sensorimotor transformations in the brain. In particular, the initiation phase of pursuit can be understood as a transformation of a sensory estimate of target velocity into an eye rotation. Despite careful laboratory controls on the stimulus conditions, pursuit eye movements are frequently observed to exhibit considerable trial-to-trial variability. In theory, this variability can be caused by the variability in sensory representation of target motion, or by the variability in the transformation of sensory information to motor commands. Previous work has shown that neural variability in the middle temporal (MT) area is likely propagated to the oculomotor command, and there is evidence to suggest that the magnitude of this variability is sufficient to account for the variability of pursuit initiation. This line of reasoning presumes that the MT population is homogeneous with respect to its contribution to pursuit initiation. At the same time, there is evidence that pursuit initiation is strongly linked to a subpopulation of MT neurons (those with strong surround suppression) that collectively generate less motor variability. To distinguish between these possibilities, we have combined human psychophysics, monkey electrophysiology, and computational modeling to examine how the pursuit system reads out the MT population during pursuit initiation. We find that the psychophysical data are best accounted for by a model that gives stronger weight to surround-suppressed MT neurons, suggesting that variability in the initiation of pursuit could arise from multiple sources along the sensorimotor transformation.
Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda
Authors: Olupot-Olupot Peter , Prevatt Natalie , Engoru Charles , Nteziyaremye Julius , Amorut Denis , Chebet Martin , Senyondo Tonny , Ongodia Paul , Ndila Carolyne M. , Williams Thomas N. , Maitland Kathryn 
Published: March 2019

Background: Severe anaemia in children requiring hospital admission is a major public health problem in malaria-endemic Africa. Affordable methods for the assessment of haemoglobin have not been validated against gold standard measures for identifying those with severe anaemia requiring a blood transfusion, despite this resource being in short supply. Methods: We conducted a prospective descriptive study of hospitalized children aged 2 months – 12 years at Mbale and Soroti Regional Referral Hospitals, assessed to have pallor at triage by a nurse and two clinicians. Haemoglobin levels were measured using the HemoCue ® Hb 301 system (gold standard); the Haemoglobin Colour Scale; Colorimetric and Sahli’s methods. We report clinical assessments of the degree of pallor, clinicians’ intention to transfuse, inter-observer agreement, limits of agreement using the Bland-Altman method, and the sensitivity and specificity of each method in comparison to HemoCue ® Results: We recruited 322 children, clinically-assessed by the admitting nurse (n=314) as having severe (166; 51.6%), moderate (97; 30.1%) or mild (51; 15.8%) pallor. Agreement between the clinicians and the nurse were good: Clinician A Kappa=0.68 (0.60–0.76) and Clinician B Kappa=0.62 (0.53–0.71) respectively ( P<0.0001 for both). The nurse, clinicians A and B indicated that of 94/116 (81.0%), 83/121 (68.6%) and 93/120 (77.5%) respectively required transfusion. HemoCue ® readings indicated anaemia as mild (Hb10.0–11.9g/dl) in 8/292 (2.7%), moderate (Hb5.0–9.9g/dl) in 132/292 (45.2%) and severe (Hb<5.0g/dl) in 152/292 (52.1%). Comparing to HemoCue® the Sahli’s method performed best in estimation of severe anaemia, with sensitivity 84.0% and specificity 87.9% and a Kappa score of  0.70 (0.64–0.80). Conclusions: Clinical assessment of severe pallor results has a low specificity for the diagnosis of severe anaemia. To target blood transfusion Hb measurement by either Hemocue® or Sahli’s method for the cost of USD 4 or and USD 0.25 per test, respectively would be more cost-effective.
Development of Training Activities to Improve the Socio-Psychological Climate in the Workforce
Authors: Прохорова М. , Prohorova M. , Лебедева Т. , Lebedeva T. 
Published: March 2019

The article presents the results of an experiment on the development and application of training activities to improve the socio-psychological climate in the workforce of the educational organization. The theoretical substantiation of the interrelation of organizational culture and socio-psychological climate in the work collective is given, the preferred type of organizational culture for modern educational organizations is described. The results of diagnostics of the type of organizational culture and socio-psychological climate on the example of an educational organization are described, conclusions are drawn about the need for their development.
A set of training measures to improve the socio-psychological climate and the development of organizational culture is described. The results of experimental work on the implementation of the described training activities are presented, and the effectiveness of their application for the development of the work collective is proved.
Dynamic Multisourcing with Dependent Supplies
Authors: Feng Qi , Jia Justin , Shanthikumar J. George 
Published: March 2019

As multisourcing becomes a widely adopted strategy in dynamic procurement planning, firms inevitably source from suppliers with dependent material flows, and such supply dependence, created by common second-tier suppliers or a common economic environment, is often positive. We show that firms can experience significant profit loss when implementing a policy computed based on a model that ignores the dependence among suppliers’ stochastic material flows. The profit loss is particularly significant when a firm earns a low margin or faces an unreliable and fragmented supplier base. Analysis of the firm’s dynamic multisourcing strategy under dependent supply uncertainties, however, is challenging. By expanding the space of ordering decision to a class of contingency policies, we identify conditions under which the dynamic planning model has a concave transformation. This approach allows us to characterize the optimal procurement policy. Moreover, our analysis suggests that the firm may order more from a less reliable supplier than from a more reliable one who charges the same procurement cost. The order allocation to the less reliable supplier can be even larger when the capacities are more dependent. Though the analysis of our base model is conducted for dependent supply capacities that are independent across periods, we show that the results can be generalized to Markov-modulated supplies or general supply functions that are stochastically linear in midpoint. This paper was accepted by Noah Gans, stochastic models and simulation.
Fostering Entrepreneurship: Promoting Founding or Funding?
Authors: Hellmann Thomas , Thiele Veikko 
Published: March 2019

Governments across the globe are eager to foster entrepreneurial ecosystems, yet there is no consensus on what policies to use. We develop a theory about the equilibrium consequences of two canonical types of entrepreneurship policies: policies that encourage entrepreneurs to found new ventures and policies that encourage investors to fund new ventures. We distinguish between a short-term impact on current market activity versus a long-term impact on future activity. Investing in entrepreneurial ventures requires tacit knowledge that is mainly acquired through prior entrepreneurial experience, implying that the supply of capital depends on successful entrepreneurs from prior generations. Recognizing this intergenerational linkage has a profound impact on the market equilibrium and the effect of entrepreneurship policies. Our analysis identifies a rationale for using funding polices. The online appendix is available at https://doi.org/10.1287/mnsc.2018.3074 . This paper was accepted by Ashish Arora, entrepreneurship and innovation.
Efeitos imediatos do exercício de vibração de corpo inteiro na simetria térmica das pernas e tornozelos
Authors: Seixas Adérito , Mendes Joaquim , Vardasca Ricardo , Bernardo-Filho Mario , Rodrigues Sandra 
Published: March 2019

Introdução: O exercício vibratório de corpo inteiro (WBV)tornou-se uma modalidade alternativa para exercício e reabilitação.Poucos estudos abordaram o efeito desta modalidadede exercício usando a temperatura da pele como medida deresultado e menos estudaram o efeito da vibração do corpointeiro na simetria térmica. O objetivo deste estudo é avaliaro impacto da exposição aguda ao exercício de vibração nasimetria térmica da parte inferior das pernas e tornozelos emindivíduos saudáveis.Métodos: A temperatura da pele de 36 indivíduos saudáveis,não treinados, do sexo masculino e feminino, foi registadausando termografia (camara FLIR A325sc), antes e após a exposição ao exercício de vibração ou situação de controle. Todos os indivíduos foram instruídos a despir-se e a permanecer sala de exame por 15 minutos para alcançar a estabilização térmica. A temperatura ambiente e a humidade relativa foram controladas,com ausência de fluxo de ar. A Power Plate® forneceu uma estimulação mecânica com parametros definidos em uma frequência de 35 Hz, alta amplitude (5-6 mm), resultando numa aceleração máxima de 121-145 m/s2, por 5 minutos.Resultados: A simetria térmica foi maior na face anterior daperna (0,17±0,13ºC) e menor na região lateral do tornozelo(0,27±0,20ºC). A exposição aguda à WBV afetou significativamentea simetria térmica em ambos os tornozelos, nas facesanteriores e laterais (p≤0,05).Discussão: Os resultados sugerem que a exposição a um exercícioagudo de vibração (35Hz) influencia a simetria térmica dostornozelos, embora o mecanismo subjacente a essas mudançasexija que estudos futuros sejam totalmente compreendidosem indivíduos saudáveis e pacientes.Descritores: Temperatura da pele; Termografia; Vibração.
Adult Education and Dialogue
Authors: McCaster Antonette Lorraine 
Published: March 2019

Knowledge is built upon personal experiences and the information to which we have access. My area of research is in communicating the language of business (accounting) to non-business learners. I’ve found that both communication and motivation are primary factors in transformational learning. To this end, research has shown that project-based education improves student skills, and transforms the traditional classroom for both teachers and students. Combining project-based education with adult dialogue education provides a transformative method of education that encourages student-driven, collaborative project-based learning as well as opportunities for teachers to reflect upon their epistemology and pedagogy.
Opinions of pre-school teachers and pre-service teachers on values education in the pre-school period: The case of Konya province
Authors: Türkoğlu Bengü 
Published: March 2019

This study, which was carried out to determine the opinions of pre-school teachers and pre-service teachers on values education in the pre-school period, is a qualitative study. The case study design was used in the study. The study group of the research consists of 60 pre-school teachers working at independent kindergartens and nursery classes affiliated to Konya Provincial Directorate of National Education and 60 pre-service teachers studying at Necmettin Erbakan University, Department of Pre-School Education. The data in the study were collected using the “Personal Information Form” and the semi-structured interview form that consists of open-ended questions. In research results, the main factor affecting values education in the pre-school period is “family” according to the common opinions of teachers and pre-service teachers. The values that pre-school children must acquire in the family are “respect”and “love”. The values that pre-school children must acquire at pre-school education institutions are “helpfulness” and “empathy”. The type of activity used for introducing values in pre-school education is “play activity”. The values education given to pre-school children supports “social-emotional development”area. The teachers and the pre-service teachers expressed the benefit that values education given in the pre-school period provides to children in their future lives as “being a good person”. The reason for giving values education at pre-school education institutions is to “prepare the children for their future roles”.
The Homeodomain Transcription Factor NKX2.1 Is Essential for the Early Specification of Melanocortin Neuron Identity and ActivatesPomcExpression in the Developing Hypothalamus
Authors: Orquera Daniela P. , Tavella M. Belén , de Souza Flavio S.J. , Nasif Sofía , Low Malcolm J. , Rubinstein Marcelo 
Published: March 2019

Food intake is tightly regulated by a group of neurons present in the arcuate nucleus of the hypothalamus, which releasePomc-encoded melanocortins, the absence of which induces marked hyperphagia and early-onset obesity. Although the relevance of hypothalamic POMC neurons in the regulation of body weight and energy balance is well appreciated, little is known about the transcription factors that establish the melanocortin neuron identity during brain development and its phenotypic maintenance in postnatal life. Here, we report that the transcription factor NKX2.1 is present in mouse hypothalamic POMC neurons from early development to adulthood. Electromobility shift assays showed that NKX2.1 bindsin vitroto NKX binding motifs present in the neuronalPomcenhancers nPE1 and nPE2 and chromatin immunoprecipitation assays detectedin vivobinding of NKX2.1 to nPE1 and nPE2 in mouse hypothalamic extracts. Transgenic and mutant studies performed in mouse embryos of either sex and adult males showed that the NKX motifs present in nPE1 and nPE2 are essential for their transcriptional enhancer activity. The conditional early inactivation ofNkx2.1in the ventral hypothalamus prevented the onset ofPomcexpression. SelectiveNkx2.1ablation from POMC neurons decreasedPomcexpression in adult males and mildly increased their body weight and adiposity. Our results demonstrate that NKX2.1 is necessary to activatePomcexpression by binding to conserved canonical NKX motifs present in nPE1 and nPE2. Therefore, NKX2.1 plays a critical role in the early establishment of hypothalamic melanocortin neuron identity and participates in the maintenance ofPomcexpression levels during adulthood.SIGNIFICANCE STATEMENTFood intake and body weight regulation depend on hypothalamic neurons that release satiety-inducing neuropeptides, known as melanocortins. Central melanocortins are encoded byPomc, andPomcmutations may lead to hyperphagia and severe obesity. Although the importance of central melanocortins is well appreciated, the genetic program that establishes and maintains fully functional POMC neurons remains to be explored. Here, we combined molecular, genetic, developmental, and functional studies that led to the discovery of NKX2.1, a transcription factor that participates in the early morphogenesis of the developing hypothalamus, as a key player in establishing the early identity of melanocortin neurons by activatingPomcexpression. Thus,Nkx2.1adds to the growing list of genes that participate in body weight regulation and adiposity.
Ongoing Pediatric Health Care for the Child Who Has Been Maltreated
Authors: Flaherty Emalee , Legano Lori , Idzerda Sheila ,   COUNCIL ON CHILD ABUSE AND NEGLECT, Sirotnak Andrew P. , Budzak Ann E. , Gavril Amy R. , Haney Suzanne B. , Laskey Antoinette “Toni” , Messner Stephen A. , Moles Rebecca L. , Palsuci Vincent J. 
Published: March 2019

This Clinical Report was retired January 2025.
Pediatricians provide continuous medical care and anticipatory guidance for children who have been reported to state child protection agencies, including tribal child protection agencies, because of suspected child maltreatment. Because families may continue their relationships with their pediatricians after these reports, these primary care providers are in a unique position to recognize and manage the physical, developmental, academic, and emotional consequences of maltreatment and exposure to childhood adversity. Substantial information is available to optimize follow-up medical care of maltreated children. This new clinical report will provide guidance to pediatricians about how they can best oversee and foster the optimal physical health, growth, and development of children who have been maltreated and remain in the care of their biological family or are returned to their care by Child Protective Services agencies. The report describes the pediatrician’s role in helping to strengthen families’ and caregivers’ capabilities and competencies and in promoting and maximizing high-quality services for their families in their community. Pediatricians should refer to other reports and policies from the American Academy of Pediatrics for more information about the emotional and behavioral consequences of child maltreatment and the treatment of these consequences.