bluuebunny/crossref_metadata_2025_split huggingface dataset:
E-cadherin expression in macrophages dampens their inflammatory responsiveness in vitro, but does not modulate M2-regulated pathologies in vivo
Authors: Van den Bossche Jan , Laoui Damya , Naessens Thomas , Smits Hermelijn H. , Hokke Cornelis H. , Stijlemans Benoît , Grooten Johan , De Baetselier Patrick , Van Ginderachter Jo A. 
Published: July 2015

AbstractIL-4/IL-13-induced alternatively activated macrophages (M(IL-4/IL-13), AAMs or M2) are known to express E-cadherin, enabling them to engage in heterotypic cellular interactions and IL-4-driven macrophage fusion in vitro. Here we show that E-cadherin overexpression in Raw 264.7 macrophages inhibits their inflammatory response to LPS stimulation, as demonstrated by a reduced secretion of inflammatory mediators like interleukin (IL)-6, tumor necrosis factor (TNF) and nitric oxide (NO). To study the function of E-cadherin in M(IL-4/IL-13) macrophages in vivo, we generated macrophage-specific E-cadherin-deficient C57BL/6 mice. Using this new tool, we analyzed immunological parameters during two typical AAM-associated Th2-driven diseases and assessed Th2-associated granuloma formation. Although E-cadherin is strongly induced in AAMs during Taenia crassiceps helminth infections and allergic airway inflammation, its deletion in macrophages does not affect the course of both Th2 cytokine-driven diseases. Moreover, macrophage E-cadherin expression is largely redundant for granuloma formation around Schistosoma mansoni ova. Overall, we conclude that E-cadherin is a valuable AAM marker which suppresses the inflammatory response when overexpressed. Yet E-cadherin deletion in macrophages does not affect M(LPS+IFNγ) and M(IL-4) polarization in vitro, nor in vivo macrophage function, at least in the conditions tested.
Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics
Authors: Smith Quinton , Stukalin Evgeny , Kusuma Sravanti , Gerecht Sharon , Sun Sean X. 
Published: July 2015

AbstractStem cell differentiation underlies many fundamental processes such as development, tissue growth and regeneration, as well as disease progression. Understanding how stem cell differentiation is controlled in mixed cell populations is an important step in developing quantitative models of cell population dynamics. Here we focus on quantifying the role of cell-cell interactions in determining stem cell fate. Toward this, we monitor stem cell differentiation in adherent cultures on micropatterns and collect statistical cell fate data. Results show high cell fate variability and a bimodal probability distribution of stem cell fraction on small (80–140 μm diameter) micropatterns. On larger (225–500 μm diameter) micropatterns, the variability is also high but the distribution of the stem cell fraction becomes unimodal. Using a stochastic model, we analyze the differentiation dynamics and quantitatively determine the differentiation probability as a function of stem cell fraction. Results indicate that stem cells can interact and sense cellular composition in their immediate neighborhood and adjust their differentiation probability accordingly. Blocking epithelial cadherin (E-cadherin) can diminish this cell-cell contact mediated sensing. For larger micropatterns, cell motility adds a spatial dimension to the picture. Taken together, we find stochasticity and cell-cell interactions are important factors in determining cell fate in mixed cell populations.
PPARγ stimulates expression of L-type amino acid and taurine transporters in human placentas: the evidence of PPARγ regulating fetal growth
Authors: Chen Zhaoguang , He Ping , Ding Xiaoying , Huang Ying , Gu Hang , Ni Xin 
Published: July 2015

AbstractPlacental amino acid transporters and peroxisome proliferator-activated receptors (PPARs) have been implicated to placental development and therefore regulation of fetal growth. We analyzed the correlation between the expression of amino acid transporters and PPARs and investigated whether PPARs control the expression of amino acid transporters in placentas. It was found that protein expression of PPARγ and L-type amino acid transporter 1(LAT1) and 2 (LAT2) was decreased in small-for-gestational-age (SGA) placentas. LAT1, LAT2 and taurine transporter (TAUT) expression correlated to PPARγ level and birth weight. In cultured placental cells, PPARγ agonist stimulated LAT1 and LAT2 and TAUT, which was reversed by PPARγ siRNA. PPARγ up-regulation of LAT1 and TAUT was through specificity protein 1 (Sp-1) while stimulation of LAT2 expression was via induction of gene transcription. Our data suggest that PPARγ, SP-1, LAT1 and LAT2 in placentas are involved in control of fetal growth. PPARγ signaling pathway may be the therapeutic target for intrauterine growth restriction.
The Dissociation of Gefitinib Trough Concentration and Clinical Outcome in NSCLC Patients with EGFR Sensitive Mutations
Authors: Xin Shuang , Zhao Yuanyuan , Wang Xueding , Huang Yan , Zhang Jing , Guo Ying , Li Jiali , Li Hongliang , Ma Yuxiang , Chen Lingyan , Hu Zhihuang , Huang Min , Zhang Li 
Published: July 2015

AbstractGefitinib is an essential drug for NSCLC patients harboring EGFR sensitive mutations. The approved dose 250mg/day is based on limited clinical trials, this research aims to explore the relationship between drug exposure and gefitinib response. Ctrough of 87 NSCLC patients harboring EGFR sensitive mutations were determined by LC-MS/MS. The median of Ctrough was 173.9 ng/ml (P25–P75, 130.5–231.2 ng/ml) and cutoff value 200 ng/ml was determined by X-Tile. The PFS between Ctrough < 200 ng/ml and Ctrough ≥ 200 ng/ml groups were not significantly different (17.3 VS 14.8 months; p = 0.258). Ctrough was not significantly associated with rash, diarrhea and hepatotoxicity. Non-smokers enjoyed longer PFS than smokers (18.7 VS 9.3 months; p = 0.025). The results showed that, for NSCLC patients with EGFR sensitive mutations, the PFS in lower trough concentration group were not inferior to that in higher trough concentration group and dose reduction is a rational suggestion for adjustment of dose regimen for aforementioned patients. More clinical trials are warranted to explore the precision dose schedule of gefitinib.
Generation-based life table analysis reveals manifold effects of inbreeding on the population fitness in Plutella xylostella
Authors: Peng Lu , Zou Mingmin , Ren Nana , Xie Miao , Vasseur Liette , Yang Yifan , He Weiyi , Yang Guang , Gurr Geoff M. , Hou Youming , You Shijun , You Minsheng 
Published: July 2015

AbstractUnderstanding how inbreeding affects fitness is biologically important for conservation and pest management. Despite being a worldwide pest of many economically important cruciferous crops, the influence of inbreeding on diamondback moth, Plutella xylostella (L.), populations is currently unknown. Using age-stage-specific life tables, we quantified the inbreeding effects on fitness-related traits and demographic parameters of P. xylostella. Egg hatching rate, survival and fecundity of the inbred line significantly declined compared to those of the outbred line over time. The inbred P. xylostella line showed significantly lower intrinsic rate of increase (r), net reproduction rate (R0) and finite increase rate (λ) and increasing generation time (T). Inbreeding effects vary with developmental stages and the fitness-related traits can be profoundly affected by the duration of inbreeding. Our work provides a foundation for further studies on molecular and genetic bases of the inbreeding depression for P. xylostella.
What is the Best Multimodality Combination for Intraoperative Spinal Cord Monitoring of Motor Function? A Multicenter Study by the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research
Authors: Ito Zenya , Matsuyama Yukihiro , Ando Muneharu , Kawabata Shigenori , Kanchiku Tsukasa , Kida Kazunobu , Fujiwara Yasushi , Yamada Kei , Yamamoto Naoya , Kobayashi Sho , Saito Takanori , Wada Kanichiro , Satomi Kazuhiko , Shinomiya Kenichi , Tani Toshikazu 
Published: July 2015

Study Design Surgeon survey. Objective To analyze multimodal intraoperative monitoring (MIOM) for different combinations of methods based on the collected data and determine the best combination. Methods A questionnaire was sent to 72 training institutions to analyze and compile data about monitoring that had been conducted during the preceding 5 years to obtain data on the following: (1) types of monitoring; (2) names and number of diseases; (3) conditions of anesthesia; (4) condition of stimulation, the monitored muscle and its number; (5) complications; and (6) preoperative and postoperative manual muscle testing, presence of dysesthesia, and the duration of postoperative motor deficit. Sensitivity and specificity, false-positive rates, and false-negative rates were examined for each type of monitoring, along with the relationship between each type of monitoring and the period of postoperative motor deficit. Results Comparison of the various combinations showed transcranial electrical stimulation motor evoked potential (TcMEP) + cord evoked potential after stimulation to the brain (Br-SCEP) combination had the highest sensitivity (90%). The TcMEP + somatosensory evoked potential (SSEP) and TcMEP + spinal cord evoked potential after stimulation to the spinal cord (Sp-SCEP) combinations each had a sensitivity of 80%, exhibiting little difference between their sensitivity and that obtained when TcMEP alone was used. Meanwhile, the sensitivity was as low as 50% with Br-SCEP + Sp-SCEP (i.e., the cases where TcMEP was not included). Conclusions The best multimodality combination for intraoperative spinal cord monitoring is TcMEP + Br-SCEP, which had the highest sensitivity (90%), the lowest false-positive rate (6.1%), and the lowest false-negative rate (0.2%).
Chemotherapy triggers HIF-1–dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype
Authors: Lu Haiquan , Samanta Debangshu , Xiang Lisha , Zhang Huimin , Hu Hongxia , Chen Ivan , Bullen John W. , Semenza Gregg L. 
Published: July 2015

Significance
We demonstrate that glutathione biosynthesis is controlled by hypoxia-inducible factor 1 and is critical for chemotherapy-induced enrichment of breast cancer stem cells, making it an attractive therapeutic target in triple-negative breast cancer, which is the only subset of breast cancers for which there is no available targeted therapy. We also delineate a molecular mechanism in which glutathione functions as a signaling molecule to activate the breast cancer stem cell phenotype, establishing cross-talk between cancer metabolism and signal transduction. We also demonstrate that mitogen-activated protein kinase kinase (MEK)-ERK inhibitors and copper chelators have the countertherapeutic effect of inducing breast cancer stem cell enrichment.
An
in silico
method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case
Authors: Wong Anthony F , Pielmeier Ulrike , Haug Peter J , Andreassen Steen , Morris Alan H 
Published: July 2015

Abstract
Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark.
Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low.
Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P  = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P  &lt; .001), and clinically different.
Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols.
Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials.
Autonomic Nervous System
Authors: Tracy Jennifer A. , Benarroch Eduardo E. , Flemming Kelly D. 
Published: July 2015

Abstract
The autonomic nervous system is involved in many important unconscious body functions. It aids in maintaining the internal environment and responds and adapts to the external environment. The autonomic nervous system consists of peripheral components (sympathetic and parasympathetic nerves) and central components (ventrolateral medulla, nucleus ambiguus, nucleus of the solitary tract, periaqueductal gray, anterior cingulate gyrus, insular cortex, amygdala, and hypothalamus). This chapter briefly reviews the anatomy and functional components of the autonomic nervous system and the anatomical clinical correlations.
Cortical Circuitry, Networks, and Function
Authors: Jones David T. 
Published: July 2015

Abstract
The human brain is a complex information processing system whose proper functioning depends on the organization of its processing units. The scale of these processing units spans multiple levels from the genetic to systems level. A complete understanding of any 1 of these levels necessitates understanding each level because they are interdependent. Functional magnetic resonance imaging has revolutionized the understanding of the functional and structural architecture of the brain and serves as the lens through which we will review this complex system. This chapter reviews cortical circuitry and networks of the cerebral cortex.
Cellular Injury and Death
Authors: Katz Brian S. , Benarroch Eduardo E. 
Published: July 2015

Abstract
Cell death is a result of several complex interconnected mechanisms simultaneously occurring in the cell’s organelles, namely, necrosis, apoptosis, and autophagy. While different morphologically and biochemically, these processes are not mutually exclusive and commonly coexist in cell loss in vascular, inflammatory, and degenerative conditions. The 3 pathways of cellular injury and death are 1) external forced cell death or necrosis; 2) programmed nuclear cell death, including apoptosis; and 3) autophagic cell death. These processes may affect neurons, glial cells, endothelial cells, and ependymal cells. The cell death pathways differ in their triggering factors, temporal profile, biochemical mechanisms, and morphologic markers.
Psychological Development Through the Life Cycle
Authors: Lapid Maria I. , Olsen Mark W. 
Published: July 2015

Abstract
Human development from conception to death can be viewed from a number of perspectives, including biologic, cognitive, emotional, social, and moral. This chapter reviews major features of various facets of development from infancy through toddlerhood, preschool, school-aged, preadolescence, adolescence, the transition into early adulthood, adulthood, and late adulthood. It includes consideration of developmental tasks and challenges as well as the importance of the environmental influence of family, peers, school, and the broader social milieu. Psychological aspects and specific stages in the elderly are also described.
Psychiatric Disorders Associated With Infancy, Childhood, and Adolescence
Authors: Bhagia Jyoti 
Published: July 2015

Abstract
This chapter covers key psychiatric disorders of infancy, childhood, and adolescence (eg, ADHD, learning disorder, autism spectrum disorder, mental retardation, tic disorders, motor skills disorder, communication disorders, elimination disorders). In some instances, the disorders are briefly mentioned here and covered in more detail in other chapters as indicated.
Substance Use Disorders
Authors: Dolenc Tamara J. 
Published: July 2015

Abstract
Substance dependence is a chronic, relapsing illness. Episodes of intoxication are common, along with significant medical and social consequences. Substance dependence is accompanied by loss of control over the amount used, continued use despite negative consequences, preoccupation with use, and dysphoria during abstinence. In heavy and long-term users, abrupt cessation or reduction in substance use results in withdrawal syndrome. Risk of substance dependence is influenced by genetic, psychosocial, and environmental factors. Patients with substance use disorders come from all age groups and from all ethnic, cultural, and socioeconomic backgrounds.
Small cell lung cancer (SCLC) and syndrome of inappropriate antidiurectic hormone (SIADH)
Authors: Darby Angela , Lee Alex 
Published: July 2015

Abstract
Small cell lung cancer (SCLC) is a smoking-associated malignancy. Accounting for 15-20% of lung cancers, the onset is typically rapid. In localized disease, surgical resection can be considered. High rates of response to first-line chemotherapy are seen, with the addition of concurrent radiotherapy improving survival in disease restricted to the ipsilateral hemithorax, as illustrated by this case. Prophylactic cranial irradiation, following response to induction therapy, reduces the rate of brain metastases and prolongs survival. Disease relapse occurs in a large proportion of cases, frequently within 1 year of induction treatment. Second-line options have a modest impact, in terms of response and survival. So far, there has been limited success of novel targeted agents in the treatment of SCLC treatment. This case discusses the recurrence of SCLC with the syndrome of inappropriate anti-diuretic hormone (SIADH) secretion. It is the cancer most commonly associated with paraneoplastic endocrine and neurological syndromes.
Ovarian cancer and malignant bowel obstruction
Authors: McNeish Iain , Chau Caroline 
Published: July 2015

Abstract
Ovarian cancer typically presents at an advanced stage and requires a multidisciplinary approach in its management. This chapter covers the diagnosis, evidence-based treatments, and recent advances in ovarian cancer. The case study outlines the presentation and clinical course of a patient with advanced ovarian cancer. It summarizes the role of surgery, chemotherapy, and bevacizumab in first-line and in disease relapse settings, with reference to landmark trials such as ICON4, ICON7, OCEANS, and CALYPSO. Bowel obstruction is a common complication of this disease, seen in the acute oncology setting. Topical issues, such as routine germline BRCA1/2 testing and CA125 monitoring, have also been discussed.
Metastatic prostate cancer and spinal cord compression
Authors: O’Donnell Helen , Bhattacharya Indrani 
Published: July 2015

AbstractThe managements of localized and metastatic prostate cancer are distinct. Prostate cancer management has undergone many changes, due to developments in our understanding of the natural history of prostate cancer and its response to treatment, and the introduction of functional imaging and technological advances in both radiotherapy and surgery. This case demonstrates the issues surrounding diagnosis and risk stratification of prostate cancer, such that treatment options can be presented and an informed decision made. The issue of prostate-specific antigen recurrence, subsequent metastatic disease, and its sequelae are discussed. There have been significant advances in drug development in metastatic prostate cancer, which have been discussed, as well as the diagnosis and management of spinal cord compression. The limitations of success from radical local treatment relate either to resistant disease locally or the presence of early micrometastatic disease at diagnosis, which is not treated with local therapy.
Characterization of systemic disease in primary Sjögren's syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements
Authors: Ramos-Casals Manuel , Brito-Zerón Pilar , Seror Raphaèle , Bootsma Hendrika , Bowman Simon J. , Dörner Thomas , Gottenberg Jacques-Eric , Mariette Xavier , Theander Elke , Bombardieri Stefano , De Vita Salvatore , Mandl Thomas , Ng Wan-Fai , Kruize Aike , Tzioufas Athanasios , Vitali Claudio ,   on behalf of the EULAR Sjögren Syndrome Task Force
Published: July 2015

Abstract
Objective. To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS.
Methods. The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features.
Results. The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ.
Conclusion. The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines.