bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: a randomized controlled trial
Authors: Pivetta Emanuele , Goffi Alberto , Nazerian Peiman , Castagno Davide , Tozzetti Camilla , Tizzani Pietro , Tizzani Maria , Porrino Giulio , Ferreri Enrico , Busso Valeria , Morello Fulvio , Paglieri Cristina , Masoero Monica , Cassine Elisa , Bovaro Federica , Grifoni Stefano , Maule Milena M. , Lupia Enrico ,   on behalf of the Study Group on Lung Ultrasound from the Molinette and Careggi Hospitals
Published: January 2019

Aims

Although acute decompensated heart failure (ADHF) is a common cause of dyspnoea, its diagnosis still represents a challenge. Lung ultrasound (LUS) is an emerging point‐of‐care diagnostic tool, but its diagnostic performance for ADHF has not been evaluated in randomized studies. We evaluated, in patients with acute dyspnoea, accuracy and clinical usefulness of combining LUS with clinical assessment compared to the use of chest radiography (CXR) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in conjunction with clinical evaluation.

Methods and results

This was a randomized trial conducted in two emergency departments. After initial clinical evaluation, patients with acute dyspnoea were classified by the treating physician according to presumptive aetiology (ADHF or non‐ADHF). Patients were subsequently randomized to continue with either LUS or CXR/NT‐proBNP. A new diagnosis, integrating the results of both initial assessment and the newly obtained findings, was then recorded. Diagnostic accuracy and clinical usefulness of LUS and CXR/NT‐proBNP approaches were calculated. A total of 518 patients were randomized. Addition of LUS had higher accuracy [area under the receiver operating characteristic curve (AUC) 0.95] than clinical evaluation alone (AUC 0.88) in identifying ADHF (P < 0.01). In contrast, use of CXR/NT‐proBNP did not significantly increase the accuracy of clinical evaluation alone (AUC 0.87 and 0.85, respectively; P > 0.05). The diagnostic accuracy of the LUS‐integrated approach was higher then that of the CXR/Nt‐proBNP‐integrated approach (AUC 0.95 vs. 0.87, p < 0.01). Combining LUS with the clinical evaluation reduced diagnostic errors by 7.98 cases/100 patients, as compared to 2.42 cases/100 patients in the CXR/Nt‐proBNP group.

Conclusion

Integration of LUS with clinical assessment for the diagnosis of ADHF in the emergency department seems to be more accurate than the current diagnostic approach based on CXR and NT‐proBNP.
1‐D Polymeric Iron(II) Thiolato Complexes: Synthesis, Structure, and Properties of ∞1[Fe(SR)2] (R = Ph, Mes), ∞1[Fe(NH3)(SPh)(µ‐SPh)] and ∞1[(µ‐SPh)Fe(NH3)2(µ‐SPh)2Fe(µ‐SPh)]
Authors: Eichhöfer Andreas , Buth Gernot
Published: January 2019

The first examples of polymeric homoleptic iron(II) thiolato complexes ∞1[Fe(SPh)2] and ∞1[Fe(SMes)2] (Ph = phenyl = C6H5, Mes = mesityl = C6H2–2,4,6‐(CH3)3) have been both prepared by reaction of [{Fe(N(SiMe3)2)2}2] with four equivalents of HSR ( R = Ph, Mes). In the crystal the two compounds form one‐dimensional chains with bridging thiolato ligands comprising distinctly different Fe–S–Fe bridging angles namely 75.20–75.25° in ∞1[Fe(SPh)2] and 91.38° in ∞1[Fe(SMes)2]. Reaction of ∞1[Fe(SPh)2] with stoichiometric amounts of NH3, generated by reaction of HN(SiMe3)2 with CH3OH, resulted in the formation of the polymeric ammonia thiolato complexes ∞1[Fe(NH3)(SPh))(µ‐SPh)] and ∞1[(µ‐SPh)Fe(NH3)2(µ‐SPh)2Fe(µ‐SPh)], which crystallize in the form of two structural isomers comprising either one or two µ2‐bridging phenyl‐thiolato groups with a bridging angle of 102.96° and 81.79–83.52°, respectively. Magnetic measurements reveal that this bridging angle has a distinct influence on the antiferromagnetic exchange interactions of the unpaired electrons along the chains in the different compounds. UV‐vis‐NIR spectra indicate low lying d‐d transitions (< 10000 cm–1) for all complexes.
Further Evidence on the Removal of Polycyclic Aromatic Hydrocarbons (PAHs) During Refining of Olive Pomace Oil
Authors: Kiralan S. Sezer , Toptancı İsra , Tekin Aziz
Published: January 2019

Influences of chemical refining parameters on the removal of 15 polycyclic aromatic hydrocarbons (PAHs) from a list of 16 EPA‐priority pollutant PAHs are investigated. For this purpose, various process conditions for each refining stages (degumming, neutralization, bleaching, and deodorization) are applied to crude olive pomace oil and the changes in PAH concentrations are monitored using a high performance liquid chromatography with florescence detector. Results show that total PAH content of the oil is reduced effectively through all refining stages. Degumming has considerable effects on removal of individual PAHs depending upon water or acid application while the most significant reduction in total PAH is achieved when 1% water is used. Neutralization has a significant impact on removal of PAHs from the oil, however, washing steps have limited effects. Using various amounts (0.3, 0.6, and 0.9%) of activated carbon in 3% of bleaching earth are more effective on the reduction of total and heavy PAHs from the oil and the most reduction is achieved when 0.9% activated carbon is used. Deodorization is effective mainly on decreases in light PAHs while temperature incrementation does not have any significant impact on the reduction in total PAH content.

Practical Applications: Olive pomace oil may include high amounts of PAHs. Because of their potential carcinogenic character, removal of PAHs from the oils has a great importance for oil acceptability. Results of this study provide information about the effects of process conditions of degumming, neutralization, bleaching, and deodorization on PAH reduction in olive pomace oil. These results might open up new process strategies in production of high quality olive pomace oil via refining.

Crude olive pomace oil may include high amounts of polycyclic aromatic hydrocarbons (PAHs) which are carcinogenic and mutagenic, depending upon drying conditions of olive pomace before extraction. They need to be removed from the oil before consumption. In this study, effects of chemical refining parameters are investigated on the removal of 15 PAHs from olive pomace oil. All refining steps, mainly neutralization and active carbon application in bleaching, have significant impacts on reducing PAHs in the oil while increasing temperature during deodorization do not have considerable effect.
Nonstationarity in peaks‐over‐threshold river flows: A regional random effects model
Authors: Eastoe E. F.
Published: January 2019

Under the influence of local‐ and large‐scale climatological processes, extreme river flow events often show long‐term trends, seasonality, interyear variability, and other characteristics of temporal nonstationarity. Properly accounting for this nonstationarity is vital for making accurate predictions of future floods. In this paper, a regional model based on the generalised Pareto distribution is developed for peaks‐over‐threshold river flow data sets when the event sizes are nonstationary. If observations are nonstationary and covariates are available, then extreme‐value (semi)parametric regression models may be used. Unfortunately, the necessary covariates are rarely observed, and if they are, it is often not clear which process, or combination of processes, to include in the model. Within the statistical literature, latent process (or random effects) models are often used in such scenarios. We develop a regional time‐varying random effects model that allows identification of temporal nonstationarity in event sizes by pooling information across all sites in a spatially homogeneous region. The proposed model, which is an instance of a Bayesian hierarchical model, can be used to predict both unconditional extreme events such as them‐year maximum and extreme events that condition on being in a given year. The estimated random effects may also tell us about likely candidates for the climatological processes that cause nonstationarity in the flood process. The model is applied to UK flood data from 817 stations spread across 81 hydrometric regions.
Comparison of textural properties and structure of gels prepared from cooked rice grain under different conditions
Authors: Sasaki Tomoko , Matsuki Junko , Yoza Koichi , Sugiyama Junichi , Maeda Hideo , Shigemune Akiko , Tokuyasu Ken
Published: January 2019

The objective of this study was to investigate the effects of rice variety, water content, and preparation temperature on the textural properties of gels processed from cooked rice grains via high‐speed shear homogenization. Rice gels were prepared from seven high‐amylose rice varieties. The results demonstrated the significant differences in rice gel hardness and hardening rates during storage based on the rice variety used. The proportion of short chains of amylopectin was negatively correlated with the hardness of the rice gel. The sample temperature before shear treatment also influenced the rice gel hardness. Rice gels prepared from cooked rice maintained at 75°C prior to homogenization showed a higher breaking force than those from cooked rice at 25°C. Observation using scanning electron microscopy demonstrated the tendency of the cooked rice sample maintained at 75°C to form a finer gel network after homogenization than those at 25°C from the same rice variety.
Age as double‐edged sword among victims of customer mistreatment: A self‐esteem threat perspective
Authors: Amarnani Rajiv K. , Restubog Simon Lloyd D. , Bordia Prashant , Abbasi Ayeesha A.
Published: January 2019

Service workers are expected to maintain high‐quality service delivery despite customer mistreatment—the poor‐quality treatment of service workers by customers—which can be demeaning and threatening to self‐esteem. Although service work is increasingly delivered by middle‐aged and older workers, very little is known about how employees across the age range navigate abuse from customers on the job. Does advancing age help or hinder service performance in reaction to customer mistreatment? Drawing on strength and vulnerability integration theory, we proposed that age paradoxically both helps and hinders performance after customer mistreatment, albeit at different stages. We tested our proposed model in a two‐sample field investigation of service workers and their supervisors using a time‐lagged, dyadic design. Results showed that age heightens the experience of self‐esteem threat but, nevertheless, dampens reactions to self‐esteem threat, leading to divergent effects on performance at different stages. Implications for age and service work, as well as aging and the sense of self, are discussed.
Study of flow field, heat transfer, and entropy generation of nanofluid turbulent natural convection in an enclosure utilizing the computational fluid dynamics‐artificial neural network hybrid method
Authors: Sepehrnia Mojtaba , Sheikhzadeh Ghanbarali , Abaei Golnoush , Motamedian Mahdi
Published: January 2019

In this study, the turbulent natural convection of Ag‐water nanofluid in a tall, inclined enclosure has been investigated. The main objective of this study is finding the optimized angle of the enclosure with operational boundary condition in cooling from ceiling utilizing the computational fluid dynamics‐artificial neural network (CFD‐ANN) hybrid method, which has not been noticed in previous studies. To achieve this, we proposed two approaches. First, the simulations have been done with a deviation angle of 0 to 90° by using water and Ag‐water nanofluid. And second, a new prediction approach is proposed based on radial basis function artificial neural networks (RBF‐ANN) to predict the mean Nusselt number and entropy generation with the variation of Rayleigh numbers, deviation angles, and volume fractions as inputs. The results from the first approach indicate that the Rayleigh number has a considerable function in the determination of optimized angle. The results from the second approach, which used the first approach simulation results as training data set, could predict the mean Nusselt number and entropy generation with 1.4577e−022 and 1.552e−015 mean square error, respectively. Moreover, a new set of data for Rayleigh numbers, deviation angles, and volume fractions were used to test the performance of the prediction model, which shows promising and superior prospects for RBF‐ANN.
Study of magnetohydrodynamic convection between two rotating cylinders filled with casson fluid and the viscous dissipation effect
Authors: Vatsa Vanita , Kumar Anand
Published: January 2019

We have studied the forced convection of a viscous incompressible and electrically conducting non‐Newtonian Casson fluid between two rotating cylinders with viscous dissipation effect. An angular velocity and gives to inner and outer cylinders, respectively, and constant heat flux presented on the inner cylinder surface. Also, the outer cylinder is taken as insulated. Here, we have discussed three cases: (i) The inner cylinder is rotating with a constant angular velocity while the outer cylinder is at rest; (ii) Both the cylinders rotate in the identical direction with equal angular velocity; and (iii) Both the cylinders are rotating with equal angular speed but the outer cylinder rotates in the opposite direction of the inner cylinder. The governing equations are solved by numerical techniques using MATLAB Software and the results are obtained graphically.
Water reuse as an incentive to promote sustainable agriculture in Lebanon: Stakeholders’ perspectives
Authors: Massoud May A , Terkawi Malakeh , Nakkash Rima
Published: January 2019

While technical and economic feasibility of water reuse projects is requisite for implementation, issues in relation to cultural values, public acceptability, and perceptions should not be marginalized. This research focuses on examining the Lebanese stakeholders’ knowledge, perception, and attitude toward the reuse of treated wastewater and on exploring potential enabling factors. Accordingly, in-depth interviews were conducted with stakeholders from concerned ministries, Lebanese Farmers Syndicate, farmers, and religious figures. The reported perceived barriers are categorized into ethical, religious, social, and economical. Various enabling factors that can ameliorate the management of potential perceived barriers are recommended, including enforcing laws, setting new regulations and quality standards, involving the public all through the project process, ensuring regular monitoring and evaluation, and developing financial policies and mechanisms. Integr Environ Assess Manag 2019;00:000–000. © 2019 SETAC
Integrating multiple‐level molecular data to infer the distinctions between glioblastoma and lower‐grade glioma
Authors: Zhang Xiaoming , Lu Xiaoyu , Liu Zhaojun , Guan Ruoyu , Wang Jianjian , Kong Xiaotong , Chen Lixia , Bo Chunrui , Tian Kuo , Xu Si , Bai Ming , Zhang Huixue , Li Jie , Wang Lihua , Shen Jia , Guo Mian
Published: January 2019

Glioblastomas (GBMs) and lower‐grade gliomas (LGGs) are the most common malignant brain tumors. Despite extensive studies that have suggested that there are differences between the two in terms of clinical profile and treatment, their distinctions on a molecular level had not been systematically analyzed. Here, we investigated the distinctions between GBM and LGG based on multidimensional data, including somatic mutations, somatic copy number variants (SCNVs), gene expression, lncRNA expression and DNA methylation levels. We found that GBM patients had a higher mutation frequency and SCNVs than LGG patients. Differential mRNAs and lncRNAs between GBM and LGG were identified and a differential mRNA–lncRNA network was constructed and analyzed. We also discovered some differential DNA methylation sites could distinguish between GBM and LGG samples. Finally, we identified some key GBM‐ and LGG‐specific genes featuring multiple‐level molecular alterations. These specific genes participate in diverse functions; moreover, GBM‐specific genes are enriched in the glioma pathway. Overall, our studies explored the distinctions between GMB and LGG using a comprehensive genomics approach that may provide novel insights into studying the mechanism and treatment of brain tumors.
Challenging anxious cognitions or accepting them? Exploring the efficacy of the cognitive elements of cognitive behaviour therapy and acceptance and commitment therapy in the reduction of children's fear of the dark
Authors: Simon Ellin , Driessen Sabine , Lambert Ann , Muris Peter
Published: January 2019

Anxiety is highly prevalent in pre‐adolescent children. Distorted cognitions are characteristic for dysfunctional levels of anxiety. However, applying cognitive elements in pre‐adolescent children cannot be fully ascertained, as it is not until adolescence before children can apply logical and abstract reasoning in a sophisticated manner. Cognitive behaviour therapy (CBT) and acceptance and commitment therapy (ACT) both target distorted cognitions. Whereas CBT encourages children to change the content of negative cognitions by applying cognitive restructuring, ACT stimulates youth to have a more accepting attitude towards these thoughts by applying cognitive defusion. The current study examined the efficacy of applying cognitive elements and compared the cognitive elements of CBT and ACT in pre‐adolescent children. We included no behavioural elements to specifically study the developmental appropriateness of the cognitive elements in this age group. Highly anxious children, aged 8–12 years were randomised to a 30‐minute cognitive restructuring (n = 21) or cognitive defusion intervention (n = 22). Subjective fear of the dark levels, behavioural darkness toleration, and comprehension and fun associated with the interventions were assessed. Both interventions had a significantly positive impact on children's fear of the dark. Cognitive restructuring led to more favourable results on subjective fear than cognitive defusion, no differences were found for darkness toleration.
Middle School Students’ Analysis of Political Memes to Support Critical Media Literacy
Authors: Elmore Patricia G. , Coleman Julianne M.
Published: January 2019

Political memes are argumentative visual texts commonly encountered on social media. Through the strategic combination of imagery and captions, a political meme presents information as fact about a topic, an individual, or a specific group. The power of political memes can be attributed to their viral nature and their effects on public discourse and perceptions. To critically read a political meme, students must be equipped with critical media literacy skills. This article describes how action researchers engaged 56 middle school students in the rhetorical analysis of political memes with the goal of supporting critical media literacy skills through practical application. The two‐week study took place in the Southeastern United States at a rural school. Students determined that the political memes created false binaries, appealed to group identities, drew on macro and micro sociopolitical contexts, and used strategic visual arrangements to form an argument. Critical media literacy is imperative given the prevalent and viral nature of media and its effects on people and public policy.
Reducing adolescent cell phone usage using an interdependent group contingency
Authors: Jones Megan E. , Allan Allday R. , Givens Ashante’
Published: January 2019

The purpose of this study was to test the effects of an interdependent group contingency on cell phone usage in an alternative high school classroom. We used an ABAB reversal design to test the effects of the contingency on the cell phone usage of the entire class and an individual student. Results showed a reduction in the cell phone use of the class and the individual when the group contingency was in effect, demonstrating a functional relation between the contingency and student cell phone usage. These findings suggest that group contingencies may be efficacious for teachers to use within their classrooms to curb cell phone usage. Further study of this intervention is warranted to determine its generality.
Electronic cigarette liquid exposure induces flavor‐dependent osteotoxicity and increases expression of a key bone marker, collagen type I
Authors: Otero Claire E. , Noeker Jacob A. , Brown Mary M. , Wavreil Florence D.M. , Harvey Wendy A. , Mitchell Kristen A. , Heggland Sara J.
Published: January 2019

Electronic cigarettes (e‐cigarettes) are nicotine delivery devices advertised as a healthier alternative to conventional tobacco products, but their rapid rise in popularity outpaces research on potential health consequences. As conventional tobacco use is a risk factor for osteoporosis, this study examines whether exposure to electronic liquid (e‐liquid) used in e‐cigarettes affects bone‐forming osteoblasts. Human MG‐63 and Saos‐2 osteoblast‐like cells were treated for 48 hours with 0.004%‐4.0% dilutions of commercially available e‐liquids of various flavors with or without nicotine. Changes in cell viability and key osteoblast markers, runt‐related transcription factor 2 and Col1a1, were assessed. With all e‐liquids tested, cell viability decreased in a dose‐dependent manner, which was least pronounced in flavorless e‐liquids, most pronounced in cinnamon‐flavored e‐liquids and occurred independently of nicotine. Col1a1, but not runt‐related transcription factor 2, mRNA expression was upregulated in response to coffee‐flavored and fruit‐flavored e‐liquids. Cells treated with a non‐cytotoxic concentration of fruit‐flavored Mango Blast e‐liquid with or without nicotine showed significantly increased collagen type I protein expression compared to culture medium only. We conclude that the degree of osteotoxicity is flavor‐dependent and occurs independently of nicotine and that flavored e‐liquids reveal collagen type I as a potential target in osteoblasts. This study elucidates potential consequences of e‐cigarette use in bone.
Heterotopic Ossification: A Comprehensive Review
Authors: Meyers Carolyn , Lisiecki Jeffrey , Miller Sarah , Levin Adam , Fayad Laura , Ding Catherine , Sono Takashi , McCarthy Edward , Levi Benjamin , James Aaron W
Published: January 2019

Heterotopic ossification (HO) is a diverse pathologic process, defined as the formation of extraskeletal bone in muscle and soft tissues. HO can be conceptualized as a tissue repair process gone awry and is a common complication of trauma and surgery. This comprehensive review seeks to synthesize the clinical, pathoetiologic, and basic biologic features of HO, including nongenetic and genetic forms. First, the clinical features, radiographic appearance, histopathologic diagnosis, and current methods of treatment are discussed. Next, current concepts regarding the mechanistic bases for HO are discussed, including the putative cell types responsible for HO formation, the inflammatory milieu and other prerequisite “niche” factors for HO initiation and propagation, and currently available animal models for the study of HO of this common and potentially devastating condition. © 2019 The Authors.JBMR Pluspublished by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Observations on the Natural History of Camurati-Engelmann Disease
Authors: Hughes Peter , Hassan Ibrahim , Que Lorna , Mead Patricia , Lee Jessica Heejong , Love Donald R , Prosser Debra O , Cundy Tim
Published: January 2019

Camurati-Engelmann disease (OMIM 31300) is a rare cranio-tubular bone dysplasia characterized by osteosclerosis of the long bones and skull caused by dominantly-inherited mutations in the transforming growth factor beta 1 (TGFB1) gene. A wide variation in phenotype has been recognized, even within families carrying the same mutation. In addition, aspects of the natural history of the disorder, in particular whether it is always progressive or can remit spontaneously, remain uncertain. In a large kindred carrying a TGFB1 gene mutation (c.653G > A; p.R218H) we have attempted to clarify the extent of phenotypic variability and the natural history of the disease through detailed individual histories of symptoms, and skeletal imaging by both radiography and scintigraphy. Only one subject had the classical childhood onset with bone pain in the legs and gait disturbance. Eight subjects reported the onset of leg pain in their teenage years that, by their early 20s, had either resolved or persisted at a low level. Two of these eight later developed cranial nerve palsies. There was a wide variation in the radiographic appearance in adults, but disease extent and activity in long bones, as assessed by scintigraphy, was inversely correlated with age (p < 0.025). In younger subjects the radiographic and scintigraphic appearances were concordant, but in older subjects the scintigram could be quiescent despite florid radiographic changes. Sequential scintigrams in two subjects showed reduced activity in the later scan. One subject had suffered meningoencephalitis in early childhood that resulted in paresis of one arm. The affected arm showed markedly less disease involvement, implicating mechanical or growth factors in its etiology. Our data suggest that the natural history of Camurati-Engelmann disease can be benign, and that disease activity commonly attenuates in adulthood. Severe cases of childhood onset and/or with cranial nerve involvement, may occur only in a minority of mutation carriers. © 2019 American Society for Bone and Mineral Research.
Thoracic Kyphosis on Chest CT Scans Is Associated With Incident Vertebral Fractures in Smokers
Authors: van Dort Mayke J , Driessen Johanna HM , Romme Elisabeth APM , Geusens Piet , Willems Paul C , Smeenk Frank WJM , Wouters Emiel FM , van den Bergh Joop PW
Published: January 2019

Greater kyphosis angles lead to increased loading on vertebral bodies in computational models. However, results about the relationship between severity of kyphosis and incident vertebral fracture (VF) risk have been conflicting. Therefore, the aim of this study was to evaluate associations between 1) prevalent VFs and severity of kyphosis, and 2) severity of kyphosis and incident VF risk in smokers with or without chronic obstructive pulmonary disease (COPD). Former and current smokers with or without COPD were included. CT scans were made at baseline, 1-year, and 3-year follow-up. VFs were evaluated on superposed sagittal CT reconstructions. Kyphosis was measured as the angle between the lines above T4 and below T9 or T12. We included 1239 subjects (mean age 61.3 ± 8.0 years, 61.1% male, 80.6% with COPD), of whom 253 (20.4%) had a prevalent VF and 294 (23.7%) an incident VF within 3 years. Presence, number, and severity of prevalent VFs were associated with a greater kyphosis angle. The mean increase in kyphosis angle within 3 years was small but significantly greater in subjects with incident VFs compared with those without (2.2 ± 4.1 versus 1.2 ± 3.9 degrees, respectively, for T4 to T12 angle, p < 0.001). After adjustment for bone attenuation (BA) and prevalent VFs, baseline kyphosis angle was associated with incident VFs within 1 and 3 years (angle T4 to T12 per +1 SD, hazard ratio [HR] = 1.34 [1.12–1.61] and HR 1.29 [1.15–1.45], respectively). Our data showed that a greater kyphosis angle at baseline was independently associated with increased risk of incident VFs within 1 and 3 years, supporting the theory that greater kyphosis angle contributes to higher biomechanical loads in the spine. © 2019 American Society for Bone and Mineral Research.
Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice
Authors: Balenga Nariman , Koh James , Azimzadeh Pedram , Hogue Joyce , Gabr Mostafa , Stains Joseph P , Olson John A
Published: January 2019

The relationship between impaired calcium sensing, dysregulated parathyroid hormone (PTH) secretion, and parathyroid cell proliferation in parathyroid neoplasia is not understood. We previously reported that a GTPase activating protein, regulator of G-protein signaling 5 (RGS5) is overexpressed in a subset of parathyroid tumors associated with primary hyperparathyroidism (PHPT) and that RGS5 can inhibit signaling from the calcium-sensing receptor (CASR). In vivo, we found that RGS5-null mice have abnormally low PTH levels. To gain a better understanding of the potential role of RGS5 overexpression in parathyroid neoplasia and PHPT and to investigate whether inhibition of CASR signaling can lead to parathyroid neoplasia, we created and characterized a transgenic mouse strain overexpressing RGS5 specifically in the parathyroid gland. These mice develop hyperparathyroidism, bone changes reflective of elevated PTH, and parathyroid neoplasia. Further, expression of exogenous RGS5 in normal human parathyroid cells results in impaired signaling from CASR and negative feedback on PTH secretion. These results provide evidence that RGS5 can modulate signaling from CASR and support a role for RGS5 in the pathogenesis of PHPT through inhibition of CASR signaling. © 2019 American Society for Bone and Mineral Research.
Mesenchymal Cell-Derived Juxtacrine Wnt1 Signaling Regulates Osteoblast Activity and Osteoclast Differentiation
Authors: Wang Fan , Tarkkonen Kati , Nieminen-Pihala Vappu , Nagano Kenichi , Majidi Rana Al , Puolakkainen Tero , Rummukainen Petri , Lehto Jemina , Roivainen Anne , Zhang Fu-Ping , Mäkitie Outi , Baron Roland , Kiviranta Riku
Published: January 2019

Human genetic evidence demonstrates that WNT1 mutations cause osteogenesis imperfecta (OI) and early-onset osteoporosis, implicating WNT1 as a major regulator of bone metabolism. However, its main cellular source and mechanisms of action in bone remain elusive. We generated global and limb bud mesenchymal cell–targeted deletion of Wnt1 in mice. Heterozygous deletion of Wnt1 resulted in mild trabecular osteopenia due to decreased osteoblast function. Targeted deletion of Wnt1 in mesenchymal progenitors led to spontaneous fractures due to impaired osteoblast function and increased bone resorption, mimicking the severe OI phenotype in humans with homozygous WNT1 mutations. Importantly, we showed for the first time that Wnt1 signals strictly in a juxtacrine manner to induce osteoblast differentiation and to suppress osteoclastogenesis, in part via canonical Wnt signaling. In conclusion, mesenchymal cell-derived Wnt1, acting in short range, is an essential regulator of bone homeostasis and an intriguing target for therapeutic interventions for bone diseases. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Long-Term Treatment With TNF-Alpha Inhibitors Improves Bone Mineral Density But Not Vertebral Fracture Progression in Ankylosing Spondylitis
Authors: Beek Kimberley Johanna , Rusman Tamara , van der Weijden Maria Alida Cornelia , Lems Willem Frederik , van Denderen Johannes Christiaan , Konsta Maria , Visman Ingrid , Nurmohamed Michael Twahier , van der Horst-Bruinsma Irene Eva
Published: January 2019

The aim of this cohort study was to evaluate the long-term effects of TNF inhibitors (TNFis) on BMD and the incidence of vertebral fractures (VFxs) in patients with ankylosing spondylitis (AS). Consecutive patients with active AS with TNFi treatment duration up to 4 years with available DXA scans and spine X-rays were included. BMD (classified according to the WHO criteria for osteoporosis) of the hip and lumbar spine, the VFx (classified as a Genant score text-decoration:underline1/text-decoration:underline20% height loss), and radiological progression (modified stoke ankylosing spondylitis spinal score [mSASSS]) scores were obtained at baseline and at 4 years of TNFi treatment. Overall, 135 AS patients were included. At baseline, 40.1% of patients had low BMD of the hip and 40.2% of the lumbar spine. This decreased to 38.1% (p = 0.03) with low hip BMD and 25.3% (p < 0.001) of the lumbar spine BMD after 4 years of TNFi treatment. VFxs were present at baseline in 11.1% of the 131 patients, which increased to 19.6% after 4 years of TNFi treatment. A Genant score ≥2, was found at baseline in 3 out of 14 VFx (21.4%) patients, which increased to 7 out of 27 VFx (25.9%) patients after 4 years. All disease activity parameters—the ankylosing spondylitis disease activity scale, the C-reactive protein, the erythrocyte sedimentation rate, and the bath ankylosing spondylitis disease activity index—decreased significantly (p < 0.001). The mean radiological progression (n = 80) increased significantly from a median mSASSS of 4.0 (1.5 to 16.0) at baseline to 6.5 (2.1 to 22.9) after 4 years of TNFi treatment (p < 0.001). Despite the improvement in BMD and the decrease in disease activity, we still found new VFxs, an increase in severity in the number and grade of VFxs, and radiographic progression during 4 years of treatment with TNFis in AS patients with long disease duration. © 2019 American Society for Bone and Mineral Research.
Hyperuricemia and gout are associated with cancer incidence and mortality: A meta‐analysis based on cohort studies
Authors: Xie Yuxiu , Xu Peng , Liu Kang , Lin Shuai , Wang Meng , Tian Tian , Dai Cong , Deng Yujiao , Li Na , Hao Qian , Zhou Linghui , Dai Zhijun , Guo Hui
Published: January 2019

The association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta‐analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose–response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04–1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03–1.11; females, RR = 1.06; 95% CI, 0.96–1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05–1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09–1.45; males, RR = 1.02; 95% CI, 0.80–1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01–1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99–1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12–1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution.
Long noncoding RNA FEZF1‐AS1 predicts poor prognosis and modulates pancreatic cancer cell proliferation and invasion through miR‐142/HIF‐1α and miR‐133a/EGFR upon hypoxia/normoxia
Authors: Ou Zheng‐Lin , Zhang Min , Ji Lian‐Dong , Luo Zhen , Han Tong , Lu Ye‐Bin , Li Yi‐Xiong
Published: January 2019

Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment‐resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR‐142/HIF‐1α and miR‐133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1‐AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR‐142 and miR‐133a; thus, we hypothesized that FEZF1‐AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1‐AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR‐142/HIF‐1α axis under hypoxic condition; however, FEZF1‐AS1 failed to affect the protein levels of HIF‐1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1‐AS1 could target miR‐133a to inhibit its expression; under the normoxic condition, FEZF1‐AS1 exerted its effect on PC cell lines through miR‐133a/EGFR axis. Taken together, FEZF1‐AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines.
Fabrication of novel combinatorial drug encapsulated micelles for enhanced tumor targeting in intestinal cancer in mouse model
Authors: Yu Haixiang , Zhang Chunpeng , Zhang Kai , Zhou Yangyang , Li Chunsheng
Published: January 2019

Hindrance to successful therapy of colon cancer is generally characterized with reduced potency of a single drug at the active site of cancer, poor drug release, and most importantly, potential toxic side effects of the drug resulting in cytotoxicity. Therefore, we investigated combinatorial drug micelles which are a potent combination of twin anticancer drugs (indomethacin and piroxicam, IND+PIR mc) for successful therapeutics of colon cancer. The novel combinatorial micelles showed improved drug encapsulation efficiency, an in vitro burst release of the dual drugs, increased cytocompatibility and increased efficacy in tumor reduction (weight and volume) than in single drug micelles (IND mc or PIR mc). The improved IND+PIR MC were to have small size 150.36 ± 15.13 nm (to avoid being taken up by liver, lungs or kidney or to sediment) with poly dispersity index (PDI) value at 0.24 ± 0.01. The PDI values suggest homogenous distribution. Encapsulation efficiency of IND+PIR mc was calculated at 86%. IND+PR mc had improved biocompatibility as demonstrated by CRL‐1459™ (normal colon) cell line than IND mc or PIR mc individually. The in vivo studies in mice model clearly depict that subcutaneous tumor weight reduced by almost 75% and volume reduced drastically by 55% on administration of IND+PIR mc than IND mc or PIR mc. Furthermore, fewer side effects were found with IND+PIR mc. To conclude, IND+PIR mc may be a potential anticancer strategy to be explored more in the future.
GABAergic regulation of pancreatic islet cells: Physiology and antidiabetic effects
Authors: Wang Qinghua , Ren Liwei , Wan Yun , Prud'homme Gerald J.
Published: January 2019

Diabetes occurs when pancreatic β‐cell death exceeds β‐cell growth, which leads to loss of β‐cell mass. An effective therapy must have two actions: promotion of β‐cell replication and suppression of β‐cell death. Previous studies have established an important role for γ‐aminobutyric acid (GABA) in islet‐cell hormone homeostasis, as well as the maintenance of the β‐cell mass. GABA exerts paracrine actions on α cells in suppressing glucagon secretion, and it has autocrine actions on β cells that increase insulin secretion. Multiple studies have shown that GABA increases the mitotic rate of β cells. In mice, following β‐cell depletion with streptozotocin, GABA therapy can restore the β‐cell mass. Enhanced β‐cell replication appears to depend on growth and survival pathways involving Akt activation. Some studies have also suggested that it induces transdifferentiation of α cells into β cells, but this has been disputed and requires further investigation. In addition to proliferative effects, GABA protects β cells against injury and markedly reduces their apoptosis under a variety of conditions. The antiapoptotic effects depend at least in part on the enhancement of sirtuin‐1 and Klotho activity, which both inhibit activation of the NF‐κB inflammatory pathway. Importantly, in xenotransplanted human islets, GABA therapy stimulates β‐cell replication and insulin secretion. Thus, the intraislet GABAergic system is a target for the amelioration of diabetes therapy, including β‐cell survival and regeneration. GABA (or GABAergic drugs) can be combined with other antidiabetic drugs for greater effect.
Hypolipidemic effects of Rosmarinus officinalis L
Authors: Farkhondeh Tahereh , Samarghandian Saeed , Pourbagher‐Shahri Ali Mohammad
Published: January 2019

Dyslipidemia is one of the major risk factors for cardiovascular diseases (CVDs). Current strategies are not effective in the management of dyslipidemia. Thus, there is a necessity to find new preventative and therapeutic approaches. In recent years, herbal medicine has drawn great attention regarding the prevention and management of dyslipidemia. Rosmarinus officinalis, commonly known as rosemary, is an evergreen shrub containing several polyphenols. The plant grows in the Mediterranean and South American regions. Rosemary and its main components have antioxidant, anti‐inflammatory, and lipid‐lowering properties. The present review has focused on in vivo and in vitro studies on the hypolipidemic effects of rosemary and its main constituents as well as their functional mechanisms. Studies have described lipid‐scavenging activities of rosemary through its ﬂavonoid contents. Modulating inflammation and oxidative stress have been described as possible mechanisms by which rosemary ameliorates dyslipidemia. However, the exact mechanisms are not fully understood yet. Conducting experimental and clinical trial studies are recommended to conﬁrm the safety and efficacy of rosemary in the prevention and management of dyslipidemia and other cardio‐metabolic diseases.
Advanced strategies for combating bacterial biofilms
Authors: Sharahi Javad Yasbolaghi , Azimi Taher , Shariati Aref , Safari Hossein , Tehrani Melika Khanzadeh , Hashemi Ali
Published: January 2019

Biofilms are communities of microorganisms that are formed on and attached to living or nonliving surfaces and are surrounded by an extracellular polymeric material. Biofilm formation enjoys several advantages over the pathogens in the colonization process of medical devices and patients' organs. Unlike planktonic cells, biofilms have high intrinsic resistance to antibiotics and sanitizers, and overcoming them is a significant problematic challenge in the medical and food industries. There are no approved treatments to specifically target biofilms. Thus, it is required to study and present innovative and effective methods to combat a bacterial biofilm. In this review, several strategies have been discussed for combating bacterial biofilms to improve healthcare, food safety, and industrial process.
Identification of Sox10‐positive cells at the dorsal fin base of juvenile flounder that are correlated with blind‐side skin ectopic pigmentation
Authors: Togawa Mai , Endo Yuna , Suzuki Nobuo , Yokoi Hayato , Suzuki Tohru
Published: January 2019

Flounder develop left‐right asymmetric body color, with a dark ocular side and white blind side. However, ectopic pigmentation often occurs on the blind side when juveniles are reared in tanks. To examine the developmental mechanism underlying ectopic pigmentation, we first examined the pigmentation process on the blind side and the localization of chromatoblasts during spontaneous and regeneration‐stimulated ectopic pigmentation. Wild‐caught juveniles that had completed metamorphosis in a natural environment were reared in tanks, where they exhibited ectopic pigmentation on the blind side that was initiated at the base of the dorsal and anal fins, with chromatoblasts appearing at the edges of scales and melanophores spreading on the scale papilla beneath the epidermis. During tissue regeneration at the base of the dorsal fin in juvenile before ectopic pigmentation, melanophores and chromatoblasts newly appeared on regenerated blind‐side skin, resulting in rapid pigmentation at the wounded site. During regeneration‐stimulated pigmentation, gch2‐positive chromatoblasts were detected only under the regenerated epidermis. Next, we found that Sox10‐positive cells were localized in connective tissue at the base of the dorsal fin and that when connective tissue was labeled with DiO, DiO‐labeled melanophores appeared in regenerated skin of the blind side after wounding. Therefore, we conclude that in flounder juveniles, Sox10‐positive progenitors of pigment cell lineage reside at the base of the dorsal fin and start migrating to the blind‐side skin in response to specific stimuli, resulting in ectopic pigmentation. Ectopic pigmentation in flounder could be a good model for examining the flexibility of pigment cell differentiation.
Talking across generations: Family communication aboutBRCA1andBRCA2genetic cancer risk
Authors: Young Alison Luk , Butow Phyllis N. , Rhodes Paul , Tucker Katherine M. , Williams Rachel , Healey Emma , Wakefield Claire E.
Published: January 2019

While family communication about aBRCA1orBRCA2(BRCA1/2) pathogenic variant can be a catalyst for the uptake of risk‐reducing measures in young adults, disseminating information within families and across generations is complex. This study aimed to explore how young adults and their families communicate about aBRCA1/2pathogenic variant, from a family systems perspective. In‐depth family interviews and questionnaires (N = 67 individuals; 21 families) were completed at four metropolitan and regional genetic clinics in Australia. Data involved thematic analysis and interpretation based on family systems theory, including the use of standardized measures. Six key themes were identified and explored: (1) Responsibility to protect, (2) “It's a woman's problem,” (3) Family culture influences communication, (4) Adversarial growth and connection, (5) Key events can be relational turning points, and (6) Health professionals can help. Family identities were solidified through the incorporation of a pathogenic variant in family scripts, while members of the family who held differing views to their families expressed less agreeableness and openness to disseminate information. The collective family's experience and perspective toward a pathogenic variant can influence a young adult's decision‐making about genetic testing, risk‐management, and family planning. The utilization of family therapy skills in routine practice would be helpful in facilitating communication and the inclusion of standardized measures is beneficial to identify individuals needing ongoing psychological support. Understanding relationship difficulties that arise from family members holding divergent views can offer insight into future research inquiry and areas of further training and clinical support.
An Efficient One‐Pot Synthesis of 7,7‐Dimethyl‐2‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐aryl‐7,8‐dihydroquinolin‐5(6H)‐one Derivatives Using Chitosan–SO3H as Biodegradable Organocatalyst
Authors: Perumal Rajasekar , Bathrinarayanan Balaji , Ghashang Majid , Mansoor Syed Sheik
Published: January 2019

Chitosan sulfonic acid (CS–SO3H), a biodegradable green catalyst, was found to be an impressive system for one‐pot four‐component reaction of different aromatic aldehydes, 3‐acetylcoumarin, dimedone, and ammonium acetate leading to 7,7‐dimethyl‐2‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐aryl‐7,8‐dihydroquinolin‐5(6H)‐one under solvent‐free condition. This methodology produces diverse superiorities such as operational simplicity, short reaction time, and high yield. Further, the catalyst can be reused for four times without any noticeable decrease in the catalytic activity.