bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIEG1 is upregulated in Lrp5/6‐mediated valve osteogenesis
Authors: Rajamannan Nalini M 
Published: September 2018

AbstractWe have previously demonstrated that Lrp5/6/β‐catenin plays an important role in valve calcification with a specific osteogenic phenotype defined by increased bone mineral content and overall valve thickening. Recent studies indicate that TIEG1 may be involved in mediating the Wnt signaling pathway in bone, which is known to play critical roles in osteoblast differentiation and bone mineralization. Therefore, we sought to test the role of TIEG1 in mediating Wnt signaling, in an established model of hypercholesterolemic valve disease. Our previous model treated null mice with cholesterol diets: Lrp5
−/−/ApoE
−/− mice versus wild‐type control (n = 180). Group I (n = 60) normal diet, Group II (n = 60) 0.25% chol diet (w/w), and Group III (n = 60) 0.25% (w/w) chol diet + atorv was tested for gene expression for TIEG1, Lrp6, and Runx2. Real‐time polymerase chain reaction confirmed that there is upregulation of the gene expression for TIEG1 and Runx2 in the hypercholesterolemic double knockout and single knockout valves as compared with controls with a mild increase in Lrp6. To confirm the mechanism, coexpression of β‐catenin, TIEG1, and LEF1 in valve cells in vitro, led to the coactivation of the TOPFLASH reporter, which was further confirmed by the observation that TIEG1 and β‐catenin colocalize with one another in the nucleus of valvular interstitial cells (VICs) following stimulation with transforming growth factor‐β treatment, an established activator of TIEG1. Taken together, these data implicate an important role for TIEG1 in mediating valve osteogenesis.
The pathogenesis of thyroid autoimmune diseases: New T lymphocytes – Cytokines circuits beyond the Th1−Th2 paradigm
Authors: Li Qian , Wang Bin , Mu Kaida , Zhang Jin‐An 
Published: September 2018

AbstractAutoimmune thyroid disease (AITD) is one of the most common organ‐specific autoimmune disorders. It mainly manifests as Hashimoto's thyroiditis (HT) and Graves’ disease (GD). HT is characteristic of hypothyroidism resulting from the destruction of the thyroid while GD is characteristic of hyperthyroidism due to excessive production of thyroid hormone induced by thyrotropin receptor‐specific stimulatory autoantibodies. T lymphocytes and their secretory cytokines play indispensable roles in modulating immune responses, but their roles are often complex and full of interactions among distinct components of the immune system. Dysfunction of these T cells or aberrant expressions of these cytokines can cause the breakdown of immune tolerance and result in aberrant immune responses during the development of AITDs. This review summarizes recently identified T subsets and related cytokines and their roles in the pathogenesis of AITDs with the hope to provide a better understanding of the precise roles of notably identified T subsets in AITDs and facilitate the discovery of functional molecules or novel immune therapeutic targets for AITDs.
Angiotensin (1–7) inhibits arecoline‐induced migration and collagen synthesis in human oral myofibroblasts via inhibiting NLRP3 inflammasome activation
Authors: You Yuehua , Huang Yun , Wang Dan , Li Yang , Wang Guozhen , Jin Siyi , Zhu Xintao , Wu Bin , Du Xinya , Li Xu 
Published: September 2018

AbstractArecoline induces oral submucous fibrosis (OSF) via promoting the reactive oxygen species (ROS). Angiotensin (1–7) (Ang‐(1–7)) protects against fibrosis by counteracting angiotensin II (Ang‐II) via the Mas receptor. However, the effects of Ang‐(1–7) on OSF remain unknown. NOD‐like receptors (NLRs) family pyrin domain containing 3 (NLRP3) inflammasome is identified as the novel mechanism of fibrosis. Whereas the effects of arecoline on NLRP3 inflammasome remain unclear. We aimed to explore the effect of Ang‐(1–7) on NLRP3 inflammasome in human oral myofibroblasts. In vivo, activation of NLRP3 inflammasomes with an increase of Ang‐II type 1 receptor (AT1R) protein level and ROS production in human oral fibrosis tissues. Ang‐(1–7) improved arecoline‐induced rats OSF, reduced protein levels of NADPH oxidase 4 (NOX4) and the NLRP3 inflammasome. In vitro, arecoline increased ROS along with upregulation of the angiotensin‐converting enzyme (ACE)/Ang‐II/AT1R axis and NLRP3 inflammasome/interleukin‐1β axis in human oral myofibroblasts, which were reduced by NOX4 inhibitor VAS2870, ROS scavenger N‐acetylcysteine, and NOX4 small interfering RNA (siRNA). Furthermore, arecoline induced collagen synthesis or migration via the Smad or RhoA‐ROCK pathway respectively, which could be inhibited by NLRP3 siRNA or caspase‐1 blocker VX‐765. Ang‐(1–7) shifted the balance of RAS toward the ACE2/Ang‐(1–7)/Mas axis, inhibited arecoline‐induced ROS and NLRP3 inflammasome activation, leading to attenuation of migration or collagen synthesis. In summary, Ang‐(1–7) attenuates arecoline‐induced migration and collagen synthesis via inhibiting NLRP3 inflammasome in human oral myofibroblasts.
2‐Methoxyestradiol attenuates chronic‐intermittent‐hypoxia‐induced pulmonary hypertension through regulating microRNA‐223
Authors: Hao Shengyu , Jiang Liyan , Fu Cuiping , Wu Xu , Liu Zilong , Song Jieqiong , Lu Huan , Wu Xiaodan , Li Shanqun 
Published: September 2018

AbstractPulmonary hypertension (PH) is prevalent in patients with obstructive sleep apnea (OSA) syndrome, and coexistence of PH and OSA indicates a worse prognosis and higher mortality. Chronic intermittent hypoxia (CIH) is the key pathogenesis of OSA. Also, microRNA‐223 (miR‐223) plays a role in the regulation of CIH‐induced PH process. However, the detailed mechanism of CIH inducing PH is still unclear. This study aimed to investigate the pathological process of CIH associated PH and explore the potential therapeutic methods. In this study, adult Sprague–Dawley rats were exposed to CIH or normoxic (N) conditions with 2‐methoxyestradiol (2‐Me) or vehicle treatment for 6 weeks. The results showed that 2‐Me treatment reduced the progression of pulmonary angiogenesis in CIH rats, and alleviated proliferation, cellular migration, and reactive oxygen species formation was induced by CIH in pulmonary artery smooth muscle cells (PASMCs). CIH decreased the expression of miR‐223, whereas 2‐Me reversed the downregulation of miR‐223 both in vivo and in vitro. Furthermore, the antiangiogenic effect of 2‐Me observed in PASMCs was abrogated by miR‐223 inhibitor, while enhanced by miR‐223 mimic. These findings suggested that miR‐223 played an important role in the process of CIH inducing PH, and 2‐Me might reverse CIH‐induced PH via upregulating miR‐223.
Tannic acid protects against experimental acute lung injury through downregulation of TLR4 and MAPK
Authors: Sivanantham Ayyanar , Pattarayan Dhamotharan , Bethunaickan Ramalingam , Kar Amrita , Mahapatra Santanu Kar , Thimmulappa Rajesh K. , Palanichamy Rajaguru , Rajasekaran Subbiah 
Published: September 2018

AbstractAcute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) remain a major cause of morbidity and mortality in critically ill patients, and no specific therapies are still available to control the mortality rate. Thus, we explored the preventive and therapeutic effects of tannic acid (TA), a natural polyphenol in the context of ALI. We used in vivo and in vitro models, respectively, using lipopolysaccharide (LPS) to induce ALI in mice and exposing J774 and BEAS‐2B cells to LPS. In both preventive and therapeutic approaches, TA attenuated LPS‐induced histopathological alterations, lipid peroxidation, lung permeability, infiltration of inflammatory cells, and the expression of proinflammatory mediators. In addition, in‐vitro study showed that TA treatment could reduce the expression of proinflammatory mediators. Further studies revealed that TA‐dampened inflammatory responses by downregulating the LPS‐induced toll‐like receptor 4 (TLR4) expression and inhibiting extracellular‐signal‐regulated kinase (ERK)1/2 and p38 mitogen‐activated protein kinase (MAPK) activation. Furthermore, cells treated with the inhibitors of ERK1/2 (PD98059) and p38 (SB203580) mitigated the expression of cytokines induced by LPS, thus suggesting that ERK1/2 and p38 activity are required for the inflammatory response. In conclusion, TA could attenuate LPS‐induced inflammation and may be a potential therapeutic agent for ALI‐associated inflammation in clinical settings.
Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs
Authors: Le Jennifer , Bradley John S. 
Published: September 2018

AbstractThe selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age‐related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population‐based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta‐lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated.
Drug Formulations: Standards and Novel Strategies for Drug Administration in Pediatrics
Authors: Thabet Yasmin , Klingmann Viviane , Breitkreutz Jörg 
Published: September 2018

AbstractChild‐appropriate drug formulations are a prerequisite of successful drug therapy in children. Efficacy and safety must be given for the active pharmaceutical ingredient, but safety also for the used excipients, components of primary packaging materials, and devices. We are presently experiencing exciting times for pediatric drug development, stimulated by previous governmental incentives in both the European Union and the United States. The most important advances in pediatric drug formulation development are reviewed and evaluated in this article. Scientific publications and recent industry strategies indicate a clear shift from liquid dosage forms to novel solid dosage forms. Solid formulations are usually composed from excipients generally regarded as safe, whereas many liquid formulations contain excipients such as preservatives, antioxidants, or taste‐masking agents that raise concerns. Further, some recent clinical studies on swallowability, acceptability, and preference indicate superiority for small‐sized tablets, so‐called mini‐tablets, over conventional liquids. In general, multiparticulate solid dosage forms could partly replace the liquids and provide more stable and cheaper alternatives to existing drug products or new developments. Dispersible solid drug dosage forms like orodispersible tablets, mini‐tablets and films are even better opportunities for efficient and safe use in pediatrics. Novel measuring and administration devices may facilitate the handling and drug administration of these modern drug dosage forms. Combination products (drug‐device combinations) can easily be linked with new e‐health technologies in near future to further improve pediatric drug therapy.
Vaccine Update: Recent Progress With Novel Vaccines, and New Approaches to Safety Monitoring and Vaccine Shortage
Authors: Ndaya‐Oloo Paul , Pitisuttithum Punnee , Tornieporth Nadia G. , Desgrandchamps Daniel , Munoz Flor M . , Kochhar Sonali , Buttery Jim , Bauwens Jorgen , Bonhoeffer Jan 
Published: September 2018

AbstractVaccines are increasingly based on new constructs, new technologies, and new compounds. Novel immunization programs are rapidly implemented globally. In this article, we highlight selected hot topics of this highly dynamic and broad field of scientific and public health development. The first section focuses on novel vaccines including malaria, dengue, serogroup B meningococcal, and respiratory syncytial virus vaccines and antibodies. The second section is addressing emerging strategies and programmatic challenges including maternal immunization, integrated mother‐child safety monitoring, and finally coping strategies with vaccine shortages.
Identifying the “Blip on the Radar Screen”: Leveraging Big Data in Defining Drug Safety and Efficacy in Pediatric Practice
Authors: Christensen Michael L. , Davis Robert L. 
Published: September 2018

AbstractThe immense amount of electronic health data (pharmacy and administrative claims, electronic health records, and clinical registries) that is being generated every day in the care of patients has the potential to be leveraged for improving clinical decisions at the point of care, uncovering or validating drug efficacy and drug safety. The potential use of big data for improving safe and effective use of medications is especially important in children because of their low drug exposure relative to adults. Electronic health data is collected primarily for clinical or billing purposes and not for research purposes. The major steps involved in data acquisition, extraction, aggregation, analysis, modeling, and interpretation are discussed. It is important to understand the limitation of big data and utilize appropriate study design and statistical methods. Possible applications are presented along with specific examples of how big data has been used in drug research to find that blip on the radar screen that may give an efficacy or safety signal that can lead to further investigation.
A dichotomy for the kernel by H‐walks problem in digraphs
Authors: Galeana‐Sánchez Hortensia , Hernández‐Cruz César 
Published: September 2018

AbstractLet be a digraph which may contain loops, and let be a loopless digraph with a coloring of its arcs . An ‐walk of is a walk of such that is an arc of , for every . For , we say that reaches by ‐walks if there exists an ‐walk from to in . A subset is a kernel by ‐walks of if every vertex in reaches by ‐walks some vertex in , and no vertex in can reach another vertex in by ‐walks.A panchromatic pattern is a digraph such that every ‐arc‐colored digraph has a kernel by ‐walks. In this study, we prove that every digraph is either a panchromatic pattern, or the problem of determining whether an arc‐colored digraph has a kernel by ‐walks is ‐complete.
Paediatric use of medications and adherence apps: a qualitative analysis of the perspectives of children and parents
Authors: Abraham Olufunmilola , Wytiaz Rebecca M. , Feathers Alison M. 
Published: September 2018

AbstractBackgroundThe number of children diagnosed with chronic medical conditions is increasing, with a high percentage struggling with medication adherence. Non‐adherence in children may lead to negative health outcomes. Parents are typically responsible for managing their child's medications. Medication adherence mobile apps are an innovative approach to address non‐adherence and actively engage children.AimThis study explored children's and parents’ perceptions of using medication adherence apps to facilitate self‐management.MethodsChildren (aged 7–17 years) taking one or more medications for a chronic condition and their parents were recruited from an outpatient pharmacy and adolescent clinic. Semistructured interviews were conducted with 8 children and 10 parents. An app interaction (guided and independent), followed by a brief questionnaire with the child was also administered. Interviews and interactions were audio recorded, transcribed and reviewed for accuracy. The technology acceptance model guided data collection and analysis. Prevalent codes were identified and thematic analysis was conducted.ResultsMost children were 12–17 years of age and most parents were 30–49 years of age. Parents and children received adherence apps as an innovative approach to the child's medication management. Nine themes emerged: ability to earn rewards for adherence; having security functionality to protect user information; customisable graphics and appealing colour schemes; medication‐specific information; ease of accessibility to mobile devices; sharing child‐friendly medication information; children's limited knowledge and involvement in medication management; and communication challenges with healthcare providers.ConclusionsAdherence apps incorporating user‐centred needs of children and educating them about chronic diseases and medication use may positively affect self‐care.
Microbial acidification, alcoholization, and aroma production during spontaneous lambic beer production
Authors: De Roos Jonas , De Vuyst Luc 
Published: September 2018

AbstractAcidic beers, such as Belgian lambic beers and American and other coolship ales, are becoming increasingly popular worldwide thanks to their refreshing acidity and fruity notes. The traditional fermentation used to produce them does not apply pure yeast cultures but relies on spontaneous, environmental inoculation. The fermentation and maturation process is carried out in wooden barrels and can take up to three years. It is characterized by different microbial species belonging to the enterobacteria, acetic acid bacteria, lactic acid bacteria, and yeasts. This review provides an introduction to the technology and four fermentation strategies of beer production, followed by the microbiology of acidic beer production, focusing on the main microorganisms present during the long process used for the production of Belgian lambic beers. © 2018 Society of Chemical Industry
Does Bowel Preparation Improve the Performance of Rectal Water Contrast Transvaginal Ultrasonography in Diagnosing Rectosigmoid Endometriosis?
Authors: Ferrero Simone , Barra Fabio , Stabilini Cesare , Vellone Valerio Gaetano , Leone Roberti Maggiore Umberto , Scala Carolina 
Published: September 2018

ObjectivesThe primary objective of the study was to compare the performance of the rectal water transvaginal ultrasonography (RWC‐TVS) with and without bowel preparation (BP) in diagnosing rectosigmoid endometriosis. The secondary objectives were to compare the performance of the 2 exams in estimating infiltration of the mucosa, length of the largest rectosigmoid nodules, distance of the nodules from the anal verge, and presence of multifocal disease.MethodsThis prospective study included patients with pain symptoms and intestinal complaints suggestive of endometriosis. Patients underwent RWC‐TVS with and without BP within an interval of 1 week to 2 months. Two independent and blinded gynecologists performed the exams. The results of the 2 exams were compared with surgical and histologic findings.ResultsA total of 155 patients were included in the study; 92 patients had rectosigmoid endometriosis. There was no significant difference in the performance of RWC‐TVS with or without BP in diagnosing rectosigmoid endometriosis (P = .727). There was no significant difference in the performance of RWC‐TVS with or without BP in diagnosing infiltration of the mucosa (P = .424) and multifocal disease (P = .688), in estimating the main diameter of the largest nodule (P = .644) and the distance between the more distal rectosigmoid nodule and the anal verge (P = .090). The patients similarly tolerated the 2 exams (P = .799).ConclusionsBowel preparation does not improve the performance of RWC‐TVS in diagnosing rectosigmoid endometriosis and in assessing the characteristics of these nodules.
Pre‐emptive action as a measure for conserving nomadic species
Authors: Stojanovic Dejan , Cook Henry C. L. , Sato Chloe , Alves Fernanda , Harris Grant , McKernan Andrew , Rayner Laura , Webb Matthew H. , Sutherland William J. , Heinsohn Robert 
Published: September 2018

ABSTRACTNomadic species are globally threatened by anthropogenic habitat change, but management options to address their decline are limited. Their unpredictable settlement patterns pose major challenges for conservation because identifying where to implement action is difficult. We address this challenge by pre‐empting settlement patterns in a nomadic species using data from a long‐term study of the critically endangered, cavity‐nesting swift parrot (Lathamus discolor) and by taking action at the sites identified. We detected flower bud growth (the primary settlement cue) and deployed artificial nests at 3 predicted breeding sites before the birds arrived. At the broad breeding‐range scale, swift parrots settled wherever bud abundance was highest, including the study area. Within the study area, artificial nest occupancy was greatest at the site with abundant historical natural nesting sites. At the local scale, we found significant effects of study site and distance to forest edges on nest box occupancy by swift parrots. Despite significant differences in thermal properties between artificial and natural nests, we found no differences in clutch size, brood size, or body condition of swift parrots in each. Monitoring settlement patterns and future food availability of nomadic wildlife can empower conservation managers to make predictions about breeding and target ecologically relevant times and locations when deploying conservation resources. Our study is an example of how conservation challenges posed by nomadic species can be overcome, and demonstrates that with effective monitoring, practical action can be targeted to address acute conservation needs and augment habitat availability. © 2018 The Wildlife Society.
The Role of Maxillofacial Prosthetics for the Surgically Treated Patient at National Cancer Institute–Designated Comprehensive Cancer Centers
Authors: Rosen Evan B. , Palin Charles L. , Huryn Joseph M. , Wong Richard J. 
Published: September 2018

Objectives/HypothesisThe current role of maxillofacial prosthetic care for head and neck cancer patients is not well understood. Additionally, perceived barriers for service provision are unknown. The purpose of this study was to evaluate the current role of maxillofacial prosthetic care at National Cancer Institute (NCI)–designated comprehensive cancer centers and to identify perceived barriers to care.Study DesignMulticenter, cross‐sectional survey of head and neck division leaders at NCI‐designated comprehensive cancer centers.MethodsEach head and neck division leader from the 47 NCI‐designated comprehensive cancer centers was invited to participate. The main outcomes of this study were: 1) to evaluate the current role of maxillofacial prosthetics for the surgically treated head and neck cancer patient within NCI‐designated comprehensive cancer centers and 2) to identify perceived barriers to care. Measured outcomes were obtained from an anonymous online survey and reported.ResultsTwenty‐eight of the 47 head and neck service chiefs responded (60% response rate). Respondents expressed preference for prosthetic rehabilitation for hard palate/upper gum, auricular, and nasal defects. Local flap or free tissue transfer was preferred for lower gum and soft palate defects. Cost‐related factors were among the most reported perceived barriers to maxillofacial prosthetic care.ConclusionsMaxillofacial prosthetics have an important role in the rehabilitation of the head and neck cancer patient. Perceived barriers for services exist, particularly as it relates to cost. Providers should be aware that these issues are likely to be more severe in regional or community centers.Level of EvidenceNA Laryngoscope, 129:409–414, 2019