bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient receptor potential channels in the context of nociception and pain – recent insights into TRPM3 properties and function
Authors: Behrendt Marc 
Published: March 2019

Abstract
Potential harmful stimuli like heat, mechanical pressure or chemicals are detected by specialized cutaneous nerve fiber endings of nociceptor neurons in a process called nociception. Acute stimulation results in immediate protective reflexes and pain sensation as a normal, physiological behavior. However, ongoing (chronic) pain is a severe pathophysiological condition with diverse pathogeneses that is clinically challenging because of limited therapeutic options. Therefore, an urgent need exists for new potent and specific analgesics without afflicting adverse effects. Recently, TRPM3, a member of the superfamily of transient receptor potential (TRP) ion channels, has been shown to be expressed in nociceptors and to be involved in the detection of noxious heat (acute pain) as well as inflammatory hyperalgesia (acute and chronic pain). Current results in TRPM3 research indicate that this ion channel might not only be part of yet unraveled mechanisms underlying chronic pain but also has the potential to become a clinically relevant pharmacological target of future analgesic strategies. The aim of this review is to summarize and present the basic features of TRPM3 proteins and channels, to highlight recent findings and developments and to provide an outlook on emerging directions of TRPM3 research in the field of chronic pain.
Adiposity and adipocytokines: the moderator role of cardiorespiratory fitness and pubertal stage in girls
Authors: Brand Caroline , Leite Neiva , Lopes Wendell Arthur , Dias Arieli Fernandes , da Silva Larissa Rosa , Araujo Gaya Adroaldo Cezar , Mota Jorge , Cavaglieri Claudia Regina , Gaya Anelise Reis 
Published: March 2019

AbstractBackgroundCardiorespiratory fitness (CRF) and pubertal stages have been related to many health outcomes, including obesity and adipocytokines. Thus, the present study aimed to analyze the moderator role of CRF and pubertal stage in the relationship between adiposity and adipocytokines in girls.MethodThis cross-sectional study was performed with 42 pre-pubertal girls aged from 7 to 11 years and 54 post-pubertal girls aged from 13 to 17 years. Blood samples were collected to determine the serum levels of leptin and adiponectin, and then the leptin/adiponectin ratio (L/A ratio) was calculated. CRF, anthropometric and body composition indicators were assessed. For statistical analysis, descriptive statistics and several linear regression models were used. The moderation analysis was tested using the PROCESS macro.ResultsAn interaction between body mass index (BMI) and CRF (β: –0.70; confidence interval [CI]: –1.29, –0.12), as well as between BMI and pubertal stage (β: 0.79; CI: 0.28, 1.30) with leptin, was found. Regarding the L/A ratio, an interaction was found only in BMI × CRF (β: –0.56; CI: –1.06, –0.06). Using a combined interaction (CRF and pubertal stage), the results showed a positive association between BMI with leptin and L/A ratio only in low CRF, pre-pubertal and post-pubertal stages.ConclusionThis study suggests a protective role of high levels of CRF in the relationship between BMI and adipocytokines. Despite the effect of pubertal stage, the results suggest that youth should be engaged in physical activity in order to improve CRF levels and consequently improve cardiometabolic health.
Reproductive senescence in free-ranging North American elk Cervus elaphus Cervidae
Authors: Bender Louis C. , Piasecke Jessica R. 
Published: March 2019

Abstract
Successful production of calves is necessary for growth of North American elk (Cervus elaphus Linnaeus 1758) populations, but few studies have evaluated age-related effects on both the conception and survival of a calf to weaning in multiple free-ranging populations. Conception and survival of calves to weaning were both affected by maternal age, with old (age 9 and older) females showing reproductive senescence as compared to prime-aged (ages 2–8) females despite achieving similar or greater size and condition. Reproductive senescence in our free-ranging populations ultimately resulted in old females weaning fewer calves (0.42 calves/female) than did prime-aged females (0.64 calves/female). Other factors, especially maternal size, also influenced conception and survival to weaning, and these interacted with age in a consistent manner, i.e. larger females or females in better condition were more likely to conceive and successfully wean calves within each age class. Female age structure receives less consideration in ungulate management than does male age structure, despite demonstrated impacts on population productivity of multiple species because of reproductive senescence. Because of the large proportion of individuals in senesced age classes in elk populations, low productivity in populations may simply reflect female age structure, rather than other frequently hypothesized factors.
Focusing attention in populations of semi-autonomously operating sensing nodes
Authors: Hildmann Hanno , Almeida Miguel , Isakovic Abdel F. , Saffre Fabrice 
Published: March 2019

Abstract
Cognition and the cognitive processing of sensory information in biological entities is known to occur over multiple layers of processing. In the example of human vision there are a vast number of photo-receptors feeding into various layers of cells which pre-process the original information before it arrives to the brain (as biased data).We propose to use a mechanism known to theoretical biologists as a means to bring about adaptive selforganization in colonies of social insects, and to apply it to such early stage signal processing. The underlying mathematical model is simple, and in the coming years, robotics will move into an era when aggregating simple computation devices into massively large collectives becomes feasible, making it possible to actually build such distributed cognitive sensing systems.
Nondestructive Corrosion Evaluation of Reinforced Concrete Bridge Decks with Overlays: An Experimental Study
Authors: Meng Dewei , Lin Shibin , Azari Hoda 
Published: March 2019

Abstract
Concrete corrosion induced by deicing agents can decrease the durability of concrete bridge decks by causing cross-sectional loss of reinforcement, concrete delamination, and spalling owing to the expansion of corroded reinforcement. The installation of overlays can extend the service life of the deteriorated decks. However, overlays present challenges in the evaluation of the corrosion condition of the underlying decks. This laboratory study employed three nondestructive testing (NDT) methods to assess the effects of seven types of overlays on corrosion evaluation for concrete bridge decks. The NDT methods were electrical resistivity (ER), ground-penetrating radar (GPR), and half-cell potential (HCP). The ER method could not evaluate the corrosive environment in the concrete decks through the overlays. The GPR method could detect the corrosive environment through four of the seven overlays. The HCP method could detect the decrease of electrical potential over the actively corroded reinforcement for all seven specimens; however, only two of the seven specimens could be identified as having active corrosion per ASTM C876-15, Standard Test Method for Corrosion Potentials of Uncoated Reinforcing Steel in Concrete. Overlay debonding did not affect GPR and HCP testing results in this study.
Brain Region-Specific Gene Signatures Revealed by Distinct Astrocyte Subpopulations Unveil Links to Glioma and Neurodegenerative Diseases
Authors: Cuevas-Diaz Duran Raquel , Wang Chih-Yen , Zheng Hui , Deneen Benjamin , Wu Jia Qian 
Published: March 2019

AbstractCurrently, there are no effective treatments for glioma or for neurodegenerative diseases because of, in part, our limited understanding of the pathophysiology and cellular heterogeneity of these diseases. Mounting evidence suggests that astrocytes play an active role in the pathogenesis of these diseases by contributing to a diverse range of pathophysiological states. In a previous study, five molecularly distinct astrocyte subpopulations from three different brain regions were identified. To further delineate the underlying diversity of these populations, we obtained mouse brain region-specific gene signatures for both protein-coding and long non-coding RNA and found that these astrocyte subpopulations are endowed with unique molecular signatures across diverse brain regions. Additional gene set and single-sample enrichment analyses revealed that gene signatures of different subpopulations are differentially correlated with glioma tumors that harbor distinct genomic alterations. To the best of our knowledge, this is the first study that links transcriptional profiles of astrocyte subpopulations with glioma genomic mutations. Furthermore, our results demonstrated that subpopulations of astrocytes in select brain regions are associated with specific neurodegenerative diseases. Overall, the present study provides a new perspective for understanding the pathophysiology of glioma and neurodegenerative diseases and highlights the potential contributions of diverse astrocyte populations to normal, malignant, and degenerative brain functions.
Development of Local Circuit Connections to Hilar Mossy Cells in the Mouse Dentate Gyrus
Authors: Shi Yulin , Grieco Steven F. , Holmes Todd C. , Xu Xiangmin 
Published: March 2019

AbstractHilar mossy cells in the dentate gyrus (DG) shape the firing and function of the hippocampal circuit. However, the neural circuitry providing afferent input to mossy cells is incompletely understood, and little is known about the development of these inputs. Thus, we used whole-cell recording and laser scanning photostimulation (LSPS) to characterize the developmental trajectory of local excitatory and inhibitory synaptic inputs to mossy cells in the mouse hippocampus. Hilar mossy cells were targeted by visualizing non-red fluorescent cells in the dentate hilus of GAD2-Cre; Ai9 mice that expressed tdTomato in GAD+ neurons, and were confirmed by post hoc morphological characterization. Our results show that at postnatal day (P)6–P7, mossy cells received more excitatory input from neurons in the proximal CA3 versus those in the DG. In contrast, at P13–P14 and P21–P28, the largest source of excitatory input originated in DG cells, while the strength of CA3 and hilar inputs declined. A developmental trend was also evident for inhibitory inputs. Overall inhibitory input at P6–P7 was weak, while inhibitory inputs from the DG cell layer and the hilus predominated at P13–P14 and P21–P28. The strength of local DG excitation and inhibition to mossy cells peaked at P13–P14 and decreased slightly in older P21–P28 mice. Together, these data provide new detailed information on the development of local synaptic connectivity of mossy cells, and suggests mechanisms through which developmental changes in local circuit inputs to hilar mossy cells shape their physiology and vulnerability to injury during postnatal periods.
Phase Coherent Currents Underlying Neocortical Seizure-Like State Transitions
Authors: Breton Vanessa , Bardakjian Berj , Carlen Peter 
Published: March 2019

AbstractIn the epileptic brain, phase amplitude cross-frequency coupling (CFC) features have been used to objectively classify seizure-related states, and the inter-seizure state has been demonstrated as being random, in contrast to the seizure state being predictable; however, the excitatory and inhibitory networks underlying their dynamics remain unclear. Therefore, the objectives of this study are to classify the dynamics of seizure sub-states labeling seizure-like event (SLE) onset and termination intervals using CFC features and to obtain their underlying excitatory/inhibitory cellular correlates. SLEs were induced in mouse neocortical brain slices using a low-magnesium perfusate, and were recorded in Layer II/III using simultaneous local field potential (LFP) and whole-cell voltage clamp electrodes. Classification of onset and termination of SLE transitions was investigated using CFC features in conjunction with an unsupervised two-state hidden Markov model (HMM). γ-Distributions of their durations indicated that both are predictable. Furthermore, omitting 4 Hz from the HMM classifier switched both SLE sub-states from statistically deterministic to random without changing the dynamics of the SLE state. These results were generalized to 4-aminopyridine (4-AP)-induced SLEs and human seizure traces. Only during these sub-states, both excitatory and inhibitory currents coupled with the field. Where excitatory currents phase locked to a broad range of frequencies between 1 and 12 Hz, inhibitory currents dominantly phase locked at 4 Hz. We conclude that inhibition underlies the predictability of neocortical CFC-defined SLE transition sub-states.
Redundant and Cryptic Enhancer Activities of theDrosophila yellowGene
Authors: Kalay Gizem , Lachowiec Jennifer , Rosas Ulises , Dome Mackenzie R , Wittkopp Patricia 
Published: March 2019

AbstractEvolutionary changes in enhancers, which control gene expression, often contribute to phenotypic evolution. Here, Kalay et al. examine how enhancer activities are encoded within non-coding sequences surrounding the pigmentation gene yellow from three Drosophila species...Cis-regulatory sequences known as enhancers play a key role in regulating gene expression. Evolutionary changes in these DNA sequences contribute to phenotypic evolution. The Drosophila yellow gene, which is required for pigmentation, has emerged as a model system for understanding how cis-regulatory sequences evolve, providing some of the most detailed insights available into how activities of orthologous enhancers have diverged between species. Here, we examine the evolution of yellow cis-regulatory sequences on a broader scale, by comparing the distribution and function of yellow enhancer activities throughout the 5′ intergenic and intronic sequences of Drosophila melanogaster, D. pseudoobscura, and D. willistoni. We find that cis-regulatory sequences driving expression in a particular tissue are not as modular as previously described, but rather have many redundant and cryptic enhancer activities distributed throughout the regions surveyed. Interestingly, cryptic enhancer activities of sequences from one species often drove patterns of expression observed in other species, suggesting that the frequent evolutionary changes in yellow expression observed among Drosophila species may be facilitated by gaining and losing repression of preexisting cis-regulatory sequences.
Una clasificación del discurso didascálico desde una perspectiva polifónica de la enunciación
Authors: Zucchi Mariano Nicolás 
Published: March 2019

En términos generales, los estudios teatrales tradicionales parecen pasar por alto el hecho de que las didascalias no constituyen un conjunto homogéneo de enunciados, sino que, por el contrario, existen una serie de diferencias formales que permiten identificar distintos subtipos, cada uno de ellos con una función específica en la construcción de sentido. Por consiguiente, en este trabajo buscamos proponer una clasificación del discurso didascálico que atienda a sus características lingüísticas específicas. Al respecto, sugerimos distinguir entre las “didascalias paratextuales” (aquellas que son externas a la narración), las “didascalias generales” (enunciados que cumplen la función de construir una representación de la situación dramática) y las “didascalias particulares” (expresiones que acompañan cada una de las réplicas de los personajes y se especializan en definir su “escenografía” (véase MAINGUENEAU, 2002)). Para probar nuestra hipótesis, nos enmarcaremos en el Enfoque dialógico de la argumentación y la polifonía enunciativa (véase GARCÍA NEGRONI, 2009, 2016a, 2016b, 2017), teoría no referencial del significado lingüístico y no unicista del sujeto. Finalmente, respecto al corpus de trabajo, haremos uso de la pieza Misterio del ramo de rosas (2009), del escritor argentino Manuel Puig, para ejemplificar los distintos subtipos que proponemos en nuestra categorización del discurso didascálico. *** Uma classificação do discurso didascálico desde uma perspectiva polifônica da enunciação ***De um modo geral, os estudos de teatro tradicionais parecem ignorar o fato de que as direções de palco não são um conjunto homogêneo de declarações, mas por outro lado, há uma série de diferenças formais que identificam diferentes subtipos, cada um com uma função específica na construção do significado. Portanto, neste artigo, procuramos propor uma classificação do discurso didascálico que aborde suas características linguísticas específicas. Neste sentido, sugerimos distinguir entre “didascalias paratextuales” (aquelas que são externas à narrativa), as “didascalias generales” (declarações que funcionam para construir uma representação da situação dramática) e as “didascalias particulares” (expressões que acompanham cada uma das réplicas dos personagens e se especializam na definição de sua “cenografia” (ver MAINGUENEAU, 2002)). Para testar a nossa hipótese, vamos enquadrar no Enfoque dialógico de la argumentación y la polifonía enunciativa (ver GARCÍA NEGRONI, 2009, 2016a, 2016b, 2017), a teoria não-referencial do significado linguístico e não unicista do assunto. Finalmente, quanto ao corpus do trabalho, vamos usar o Misterio del ramo de rosas (2009), do escritor argentino Manuel Puig, para exemplificar os diferentes subtipos que propomos na nossa categorização de expressão didascálica.Palavras-chave: Argumentação; Didascália; Polifonia; Réplica; Texto dramático.
From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for EGFR-Positive Non-Small Cell Lung Cancer (MOST Study)
Authors: Pasello Giulia , Vicario Giovanni , Zustovich Fable , Oniga Francesco , Gori Stefania , Rosetti Francesco , Bonetti Andrea , Favaretto Adolfo , Toso Silvia , Redelotti Roberta , Santo Antonio , Bernardi Daniele , Giovanis Petros , Oliani Cristina , Calvetti Lorenzo , Gatti Carlo , Palazzolo Giovanni , Baretta Zora , Bortolami Alberto , Bonanno Laura , Basso Marco , Menis Jessica , Corte Donatella Da , Frega Stefano , Guarneri Valentina , Conte PierFranco ,   on behalf of Veneto Oncology Network
Published: March 2019

Abstract

Introduction
Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice.

Methods
MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous EGFR-mutant NSCLC. We reported treatment outcome in terms of median time to treatment failure (mTTF) and assessed the impact of each agent on the expense of the regional health system, comparing it with a prediction based on the pivotal trials.

Results
An EGFR mutation test was performed in 447 enrolled patients, of whom 124 had EGFR mutation and who received gefitinib (n = 69, 55%), erlotinib (n = 33, 27%), or afatinib (n = 22, 18%) as first-line treatment. Because erlotinib was administered within a clinical trial to 15 patients, final analysis was limited to 109 patients. mTTF was 15.3 months, regardless of the type of tyrosine kinase inhibitor (TKI) used. In the MOST study, the budget impact analysis showed a total expense of €3,238,602.17, whereas the cost estimation according to median progression-free survival from pivotal phase III trials was €1,813,557.88.

Conclusion
Good regional adherence and compliance to the diagnostic-therapeutic pathway defined for patients with nonsquamous NSCLC was shown. mTTF did not significantly differ among the three targeted TKIs. Our budget impact analysis suggests the potential application of real-world data in the process of drug price negotiation.
Single-Cell RNA Profiling of Glomerular Cells Shows Dynamic Changes in Experimental Diabetic Kidney Disease
Authors: Fu Jia , Akat Kemal M. , Sun Zeguo , Zhang Weijia , Schlondorff Detlef , Liu Zhihong , Tuschl Thomas , Lee Kyung , He John Cijiang 
Published: March 2019

Significance Statement
Although transcriptomic profiling of kidney tissues or isolated glomeruli has provided insights into broad changes in the pathogenesis of diabetic kidney disease, the presence of multiple cell types in kidney samples limits what can be discerned about changes in specific types of cells. To better elucidate the mechanisms of early diabetic kidney injury, the authors used single-cell RNA sequencing technology to perform a gene expression analysis of individual kidney glomerular cells of a diabetic mouse model. A comparison of gene expression in normal versus diabetic mouse kidney cells at a single-cell level showed dynamic changes in the pattern of expressed genes. This approach may help identify important factors underlying the pathophysiology of diabetic kidney disease progression and point to potential new therapeutic approaches.

Background
Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into cell-specific gene expression profiles in normal kidneys. However, in diseased kidneys, understanding of changes in specific cells, particularly glomerular cells, remains limited.

Methods
To elucidate the glomerular cell–specific gene expression changes in diabetic kidney disease, we performed scRNA-seq analysis of isolated glomerular cells from streptozotocin-induced diabetic endothelial nitric oxide synthase (eNOS)–deficient (eNOS−/−) mice and control eNOS−/− mice.

Results
We identified five distinct cell populations, including glomerular endothelial cells, mesangial cells, podocytes, immune cells, and tubular cells. Using scRNA-seq analysis, we confirmed the expression of glomerular cell–specific markers and also identified several new potential markers of glomerular cells. The number of immune cells was significantly higher in diabetic glomeruli compared with control glomeruli, and further cluster analysis showed that these immune cells were predominantly macrophages. Analysis of differential gene expression in endothelial and mesangial cells of diabetic and control mice showed dynamic changes in the pattern of expressed genes, many of which are known to be involved in diabetic kidney disease. Moreover, gene expression analysis showed variable responses of individual cells to diabetic injury.

Conclusions
Our findings demonstrate the ability of scRNA-seq analysis in isolated glomerular cells from diabetic and control mice to reveal dynamic changes in gene expression in diabetic kidneys, with variable responses of individual cells. Such changes, which might not be apparent in bulk transcriptomic analysis of glomerular cells, may help identify important pathophysiologic factors contributing to the progression of diabetic kidney disease.