bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocyte/macrophage lineage commitment and distribution are affected by the lack of regulatory T cells in scurfy mice
Authors: Skuljec Jelena , Cabanski Maciej , Surdziel Ewa , Lachmann Nico , Brennig Sebastian , Pul Refik , Jirmo Adan C. , Habener Anika , Visic Julia , Dalüge Kathleen , Hennig Christian , Moritz Thomas , Happle Christine , Hansen Gesine
Published: May 2016

Foxp3+ regulatory T (Treg) cells play a pivotal role in maintaining immunological tolerance. Loss‐of‐function mutations in the Foxp3 gene result in multiorgan inflammation known as immunodysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome in humans and scurfy (Sf) disease in mice. While the impact of missing Treg cells on adaptive immune cells is well documented, their role in regulation of myeloid cells remains unclear. Here we report that Sf mice exhibit an altered composition of stem and progenitor cells, characterized by increased numbers of myeloid precursors and higher efficiency of macrophage generation ex vivo. The proportion of monocytes/macrophages in the bone marrow, blood, and spleen was significantly elevated in Sf mice, which was accompanied with tissue‐specific monocyte expression of homing receptor and phagocytic activity. Sf mice displayed high levels of M‐CSF and other inflammatory cytokines, including monocyte‐recruiting chemokines. Adoptive transfer of WT CD4+ cells and in vivo neutralization of M‐CSF normalized frequencies of monocyte subsets and their progenitors and reduced high levels of monocyte‐related cytokines in Sf mice, while Treg cell transfer to RAG2−/− mice had no effect on myelopoiesis and monocyte/macrophage counts. Our findings illustrate that deregulated myelopoiesis in Sf mice is mainly caused by the inflammatory reaction resulting from the lack of Treg cells.
Immunity in young adult survivors of childhood leukemia is similar to the elderly rather than age‐matched controls: Role of cytomegalovirus
Authors: Azanan Mohamad Shafiq , Abdullah Noor Kamila , Chua Ling Ling , Lum Su Han , Abdul Ghafar Sayyidatul Syahirah , Kamarulzaman Adeeba , Kamaruzzaman Shahrul , Lewin Sharon R. , Woo Yin Ling , Ariffin Hany , Rajasuriar Reena
Published: May 2016

Many treatment complications that occur late in childhood cancer survivors resemble age‐related comorbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation, and accumulation of late‐differentiated memory CD57+CD28− T cells has been associated with comorbidities in the elderly. Here, we explored if this phenotype was present in young adult leukemia survivors following an average of 19 years from chemotherapy and/or radiotherapy completion, and compared this with that in age‐matched controls. We found that markers of systemic inflammation—IL‐6 and human C‐reactive protein and immune activation—CD38 and HLA‐DR on T cells, soluble CD (sCD)163 from monocytes and macrophages—were increased in survivors compared to controls. T‐cell responses specific to cytomegalovirus (CMV) were also increased in survivors compared to controls while CMV IgG levels in survivors were comparable to levels measured in the elderly (>50years) and correlated with IL‐6, human C‐reactive protein, sCD163, and CD57+CD28− memory T cells. Immune activation and inflammation markers correlated poorly with prior chemotherapy and radiotherapy exposure. These data suggest that CMV infection/reactivation is strongly correlated with the immunological phenotype seen in young childhood leukemia survivors and these changes may be associated with the early onset of age‐related comorbidities in this group.
Fractionation‐dependent improvements in proteome resolution in the mouse hippocampus by IEF LC‐MS/MS
Authors: Bundy Joseph L. , Inouye Brian D. , Mercer Roger S. , Nowakowski Richard S.
Published: May 2016

An assessment of fractionated mouse hippocampal peptides was conducted. Protein extract from a single mouse hippocampus was enzymatically digested and fractionated by IEF. Aliquots of fractions were pooled into fewer, more complex samples. The unfractionated lysate, fractions, and pooled fractions were subjected to LC‐MS/MS analysis. Samples consisting of many individual fractions had more protein identifications, greater protein sequence coverage, and quantified proteins with more spectral counts than protein extract that was unfractionated or pooled into fewer LC‐MS/MS samples. Additionally, prefractionation reduced the median CV for spectral counts as much as 33%. However, the relative gain in proteome resolution was found to saturate with increasing fractionation extent. This study demonstrates how prefractionation by offline IEF can improve the resolution of proteomic investigations of the mouse hippocampus, and that a data‐driven pooling methodology can reduce excessive and cost‐ineffective fractionation.
Photovoltaic solar array: Modeling and output power optimization
Authors: M'hamed Houari Zerhouni , Fatima Zohra Zerhouni , Mansour Zegrar , Amar Tilmatine
Published: May 2016

Photovoltaic energy is a natural form of energy and can replace conventional fuels. The photovoltaic performance depends mainly on the incident solar irradiation, temperature, photovoltaic generator material composition. This article proposes a method of photovoltaic arrays modeling. With data provided by the manufacturer, the method finds the electric equations (current versus voltage, power versus voltage) for photovoltaic array at standard conditions. Model also takes account of temperature and insolation variations to determine novel characteristics for specific conditions. This article also discusses the use of DC–DC converter realized as a means of maximum power point tracker (MPPT). The control card obtains informations from the PV array through microcontroller's ports. Combined methods: jump to maximum power point (MPP) and power's comparison method are used as an algorithm to track the maximum power point of the PV array. Analysis experimental results were carried in order to verify the proposed method. Another purpose of this article is to model the optimal power using the methodology of experimental design. An optimization of power delivered by photovoltaic generator takes into account the insolation and temperature factors. In general, in the methods in literature, only solar irradiation variations or load variations are considered. But, the results do not reflect the conditions that occur in the real conditions. The design of experiment (DoE) technique and the response surface methodology (RSM), are employed to analyze the results of tests obtained during different climatic conditions. Results are given and analyzed in this article. Results are used to fit and adjust response surfaces to experimental data. The obtained results made it possible to propose a mathematical model and, consequently to study interactions between temperature and insolation. The DOE simulation model can be implemented in future works. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1529–1536, 2016
Artificial neural network prediction of NOx emissions from EGR and non‐EGR engines running on soybean biodiesel fuel (B5) during cold idle mode
Authors: Omidvarborna H. , Kumar A. , Kim D. S.
Published: May 2016

Artificial neural network (ANN) prediction scheme was developed for nitrogen oxides (NOx) emissions in cold idle mode based on the analysis of NOx emissions from on‐road transit buses operating on a blend of biodiesel. The input data necessary for training and testing the proposed ANN scheme was obtained from two different urban transit buses fueled with 5 vol % soybean methyl ester (SME) and 95% of ultra‐low sulfur diesel (ULSD). One bus was equipped with exhaust gas recirculation (EGR) and the other one was not. The reduction of NOx emissions was observed when EGR was implemented. A standard feed forward back‐propagation algorithm was used in this analysis and in building the network structure, whereas Levenberge–Marquardt (LM) learning algorithm was used to predict the NOx emissions. The study was carried out with 70% of total experimental data selected for training the neural network, 15% for the network's validation, and the remaining 15% data were used for testing the performance of the trained network. ANN results showed that the developed ANN model was capable of predicting the NOx emissions of the tested engines with excellent agreement (correlation coefficients: 0.99 < R < 1), while root mean square errors (RMSEs) were 22.1 and 1.7 ppm for non‐EGR and EGR‐equipped engine series, respectively. ANN provided an accurate and simple approach to the analysis of this complex, multivariate problem, where idle NOx emissions from both non‐EGR and EGR engines should be predicted. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1537–1544, 2016
Exploring Pre‐K Age 4 Learning Standards and Their Role in Early Childhood Education: Research and Policy Implications
Authors: DeBruin‐Parecki Andrea , Slutzky Carly
Published: May 2016

Currently in the United States, 50 states, 5 territories, and the District of Columbia have established prekindergarten (pre‐K) age 4 learning standards that are intended to outline skills and knowledge that set children on a path to success in kindergarten and upcoming grades. These standards are emphasized as a centralizing force in early childhood education, providing a bridge strengthening ties between preschool and elementary grades. This report presents a national study of pre‐K age 4 learning standards based on an online survey completed by early childhood state and territory directors and administrators, geographically diverse focus groups representing a subsample of survey respondents, and one‐on‐one interviews composed of a sample of both focus group and survey participants. Data were collected from these sources and by direct examination of pre‐K age 4 learning standards documents. Responses to survey, focus group, and interview questions advanced current knowledge regarding the purpose, history, and development of pre‐K age 4 learning standards, comprehensiveness of standards documents, standards‐related supports for teachers, and pre‐K to kindergarten alignment. Systematic analysis of pre‐K age 4 learning standards documents revealed extensive variation across titles, organization, terminology, and enriching materials, such as teacher strategies and child examples that assist teachers in implementing standards. A surprising finding is the positive view among early childhood leaders in focus groups and interviews toward establishing national pre‐K age 4 learning standards. The report concludes with a brief discussion of implications of this study followed by recommendations to inform state and federal early childhood leaders, education‐focused philanthropic foundations, and others in the field of early childhood education.
2D Burgers equation with large Reynolds number using POD/DEIM and calibration
Authors: Wang Yuepeng , Navon Ionel M. , Wang Xinyue , Cheng Yue
Published: May 2016

Model order reduction of the two‐dimensional Burgers equation is investigated. The mathematical formulation of POD/discrete empirical interpolation method (DEIM)‐reduced order model (ROM) is derived based on the Galerkin projection and DEIM from the existing high fidelity‐implicit finite‐difference full model. For validation, we numerically compared the POD ROM, POD/DEIM, and the full model in two cases of Re = 100 and Re = 1000, respectively. We found that the POD/DEIM ROM leads to a speed‐up of CPU time by a factor of O(10). The computational stability of POD/DEIM ROM is maintained by means of a careful selection of POD modes and the DEIM interpolation points. The solution of POD/DEIM in the case of Re = 1000 has an accuracy with error O(10−3) versus O(10−4) in the case of Re = 100 when compared with the high fidelity model. For this turbulent flow, a closure model consisting of a Tikhonov regularization is carried out in order to recover the missing information and is developed to account for the small‐scale dissipation effect of the truncated POD modes. It is shown that the computational results of this calibrated ROM exhibit considerable agreement with the high fidelity model, which implies the efficiency of the closure model used. Copyright © 2016 John Wiley & Sons, Ltd.
A spectral‐element discontinuous Galerkin thermal lattice Boltzmann method for conjugate heat transfer applications
Authors: Patel Saumil , Min Misun , Lee Taehun
Published: May 2016

We present a spectral‐element discontinuous Galerkin thermal lattice Boltzmann method for fluid–solid conjugate heat transfer applications. Using the discrete Boltzmann equation, we propose a numerical scheme for conjugate heat transfer applications on unstructured, non‐uniform grids. We employ a double‐distribution thermal lattice Boltzmann model to resolve flows with variable Prandtl (Pr) number. Based upon its finite element heritage, the spectral‐element discontinuous Galerkin discretization provides an effective means to model and investigate thermal transport in applications with complex geometries. Our solutions are represented by the tensor product basis of the one‐dimensional Legendre–Lagrange interpolation polynomials. A high‐order discretization is employed on body‐conforming hexahedral elements with Gauss–Lobatto–Legendre quadrature nodes. Thermal and hydrodynamic bounce‐back boundary conditions are imposed via the numerical flux formulation that arises because of the discontinuous Galerkin approach. As a result, our scheme does not require tedious extrapolation at the boundaries, which may cause loss of mass conservation. We compare solutions of the proposed scheme with an analytical solution for a solid–solid conjugate heat transfer problem in a 2D annulus and illustrate the capture of temperature continuities across interfaces for conductivity ratio γ > 1. We also investigate the effect of Reynolds (Re) and Grashof (Gr) number on the conjugate heat transfer between a heat‐generating solid and a surrounding fluid. Steady‐state results are presented for Re = 5−40 and Gr = 105−106. In each case, we discuss the effect of Re and Gr on the heat flux (i.e. Nusselt number Nu) at the fluid–solid interface. Our results are validated against previous studies that employ finite‐difference and continuous spectral‐element methods to solve the Navier–Stokes equations. Copyright © 2016 John Wiley & Sons, Ltd.
One‐stage reconstruction of tracheal defects with the medial femoral condyle corticoperiosteal‐cutaneous free flap
Authors: Ninkovic Milomir , Buerger Heinz , Ehrl Denis , Dornseifer Ulf
Published: May 2016

Background

The demanding anatomic and mechanical requirements make the reconstruction of long tracheal defects challenging. Multiple attempts at replacing tracheal segments are described, including the use of autologous, allogeneic, and synthetic tissues. However, the multilayer structure of the trachea and its function as a conduit for air had generally resulted in the use of nonvascularized tissue and/or multistage procedures.

Methods

The authors report on a 1‐stage autologous reconstruction using local skin flaps for inner lining and a free medial femoral condyle corticoperiosteal‐cutaneous (FCCPC) flap for the remaining layers. The skin island directly located over the FCCPC flap serves as an external coverage of the tracheal reconstruction.

Results

Within the follow‐up, the reconstructed trachea has retained its shape, diameter, and airway function. No notable stenosis or instability was observed.

Conclusion

This concept combines ideal biological and mechanical tissue properties, offering the potential to meet the reconstructive requirements for extended tracheal defects. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1870–1873, 2016
Right‐sided aortic arch and aberrant left subclavian artery with or without a left nonrecurrent inferior laryngeal nerve
Authors: Masuoka Hiroo , Miyauchi Akira , Higashiyama Takuya , Yabuta Tomonori , Kihara Minoru , Miya Akihiro
Published: May 2016

Background

In thyroid surgery, preserving the recurrent laryngeal nerve (RLN) is crucial for preventing postoperative phonatory dysfunction. Right nonrecurrent laryngeal nerves (NRLNs) are not particularly rare, and they are vulnerable to injury during surgery. This anomaly is associated with a right aberrant subclavian artery. Thus, a right‐sided aortic arch with an aberrant left subclavian artery (LSA) suggests a possible left NRLN.

Methods

We report the cases of 4 patients with right‐sided aortic arch and aberrant LSA. Preoperative imaging studies revealed those anomalies, but no signs of situs inversus. During the surgeries, only 1 of the 4 cases had a left NRLN. We retrospectively evaluated the patients' imaging studies.

Results

An aortic diverticulum was found at the point at which the aberrant LSA originated in the 3 patients with left‐RLNs, but not in the patient with the left‐NRLN.

Conclusion

In right‐sided aortic arch + aberrant LSA cases, the absence of an aortic diverticulum suggests a left NRLN. © 2016 Wiley Periodicals, Inc. Head Neck 38: First–E2511, 2016
HERG1 potassium channel expression in potentially malignant disorders of the oral mucosa and prognostic relevance in oral squamous cell carcinoma
Authors: Fernández–Valle Álvaro , Rodrigo Juan Pablo , Rodríguez–Santamarta Tania , Villaronga M. Ángeles , Álvarez–Teijeiro Saúl , García–Pedrero Juana M. , Suárez–Fernández Laura , Lequerica–Fernández Paloma , de Vicente Juan Carlos
Published: May 2016

Background

HERG1 potassium channel plays a critical role in the cell proliferation.

Methods

HERG1 protein expression was analyzed by immunohistochemistry (IHC) in 62 patients with oral leukoplakias and 100 patients with oral squamous cell carcinomas (OSCC). HERG1 mRNA levels were assessed by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) in 22 patients with primary head and neck squamous cell carcinoma (HNSCC).

Results

Statistically significant associations were found between HERG1 expression and tobacco consumption, disease stage, tumor differentiation, tumor recurrence, and reduced survival. There was no association between HERG1 expression and the risk of progression from oral leukoplakia to OSCC. In addition, a high proportion of tumors (80%) showed increased HERG1 mRNA levels compared to normal mucosa from nononcologic patients.

Conclusion

Aberrant HERG1 expression increases as oral tumorigenesis progresses from oral hyperplasia to OSCC. Increased HERG1 mRNA levels were also frequently detected in OSCC and other HNSCC subsites. HERG1 expression emerges as a clinically relevant feature during tumor progression and a potential poor prognostic biomarker for OSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708–1716, 2016
Functional outcomes of sensate versus insensate free flap reconstruction in oral and oropharyngeal reconstruction: A systematic review
Authors: Namin Arya W. , Varvares Mark A.
Published: May 2016

The purposes of this article were to review the literature regarding subjective outcomes, objective functional outcomes, and objective sensation return after sensate and/or insensate free flap reconstruction of the oral cavity and oropharynx. Sensate radial forearm and anterolateral thigh free flaps tend to have better static 2‐point discrimination and pressure threshold sensitivity than insensate flaps. There is insufficient evidence to draw conclusions on whether sensate flaps improve functional speech and swallowing outcomes measured by videofluoroscopic swallowing studies and percentage of word intelligibility by a listener blinded to the study. These data highlight the complexity and number of variables affecting functional outcomes in patients who have undergone reconstructive surgery after oral and oropharyngeal cancer ablative operations. A prospective randomized multicenter study that properly and rigidly stratifies patients by defect, flap and recipient nerve choice, adjuvant therapies, and uses widely agreed upon pretreatment and posttreatment evaluation tools could help to answer this important question. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708–1716, 2016
A semi‐analytical approach for predicting peak discharge of floods caused by embankment dam failures
Authors: Wang Bo , Chen Yunliang , Wu Chao , Dong Jianhua , Ma Xiao , Song Jiajun
Published: May 2016

This study presents an analytical solution of dam‐break floods in a trapezoidal channel with detailed solution procedure. An approach predicting the peak discharge of floods caused by embankment dam failures was derived from the aforementioned analytical solution with a database of 27 historical dam failures. The prediction performance of this approach has been proved by comparing with other 14 straightforward equations for estimating the peak discharge. The proposed model with a small uncertainty of predicted peak flow rates has a high coefficient of determination and a small standard error, being ranked in the top four of the 15 methods considered in this paper. The robustness and predictive capability of the proposed model are further demonstrated in two case studies, and both were considered in the previous analyses performed by other investigators. This method provides a simple and transparent tool for engineers to predict the peak discharge and is easy to implement for trial and error calculation. Copyright © 2016 John Wiley & Sons, Ltd.
Charred forests accelerate snow albedo decay: parameterizing the post‐fire radiative forcing on snow for three years following fire
Authors: Gleason Kelly E. , Nolin Anne W.
Published: May 2016

As large, high‐severity forest fires increase and snowpacks become more vulnerable to climate change across the western USA, it is important to understand post‐fire disturbance impacts on snow hydrology. Here, we examine, quantify, parameterize, model, and assess the post‐fire radiative forcing effects on snow to improve hydrologic modelling of snow‐dominated watersheds having experienced severe forest fires. Following a 2011 high‐severity forest fire in the Oregon Cascades, we measured snow albedo, monitored snow, and micrometeorological conditions, sampled snow surface debris, and modelled snowpack energy and mass balance in adjacent burned forest (BF) and unburned forest sites. For three winters following the fire, charred debris in the BF reduced snow albedo, accelerated snow albedo decay, and increased snowmelt rates thereby advancing the date of snow disappearance compared with the unburned forest. We demonstrate a new parameterization of post‐fire snow albedo as a function of days‐since‐snowfall and net snowpack energy balance using an empirically based exponential decay function. Incorporating our new post‐fire snow albedo decay parameterization in a spatially distributed energy and mass balance snow model, we show significantly improved predictions of snow cover duration and spatial variability of snow water equivalent across the BF, particularly during the late snowmelt period. Field measurements, snow model results, and remote sensing data demonstrate that charred forests increase the radiative forcing to snow and advance the timing of snow disappearance for several years following fire. Copyright © 2016 John Wiley & Sons, Ltd.
Anti‐asthmatic and anxiolytic effects ofHerissantia tiubae, a Brazilian medicinal plant
Authors: Mozzini Monteiro Talissa , Ferrera Costa Hermann , Carvalho Vieira Giciane , Rodrigues Salgado Paula Regina , da Silva Stiebbe Salvadori Mirian Graciela , de Almeida Reinaldo Nobrega , de Fatima Vanderlei de Souza Maria , Neves Matias Wemerson , Andrade Braga Valdir , Nalivaiko Eugene , Piuvezam Marcia Regina
Published: May 2016

Herissantia tiubae(HtE) is a Brazilian plant used in folk medicine to treat inflammatory diseases. Our aim was to determine whether the HtE has anti‐inflammatory and anxiolytic effects in a murine model of asthma. Ovalbumin (OVA)‐sensitized BALB/c mice were treated with HtE (50, 100, or 200 mg/kg) or dexamethasone before each OVA challenge. After the last challenge, animals were subjected to anxiety tests and respiratory measurements. Following euthanasia, we quantified immune cells in the bronchoalveolar lavage (BAL), serum IgE titer and cytokine levels, cellular infiltration and mucus content in the lung tissues, and cellular composition of the mediastinal lymph nodes. OVA challenge in sensitized animals caused: (1) reduction of mean respiratory and dominant respiratory rate (from 398 ± 12 to 286 ± 20 cicles per minute (cpm) and from 320 ± 14 to 162 ± 15 cpm, respectively); (2) increase in behavioral markers of anxiety tests; (3) substantial pro‐inflammatory effects, including rise in OVA‐specific IgE titer (from 0 to 1:2048) and these inflammatory effect diminished the titer to 1:512 after HtE treatment; rise in plasma IL‐13 (from 13 ng/mL in saline to 227 ng/mL in OVA and HtE treatment restored to 1.29 ng/mL; rise in total BAL cell count (from 0.742 cells/mL in saline to 11.77 cells/mL in OVA), with prominent eosinophilia.H. tiubaeextract affected respiratory parameters similarly to aminophylline, behavioral changes comparable to diazepam, and inflammation being as efficient as dexamethasone.H. tiubaeextract (HtE) possesses both anti‐inflammatory and anxiolytic properties in the murine model of asthma.
Pancreatic cancer: Wait times from presentation to treatment and survival in a population‐based study
Authors: Jooste Valérie , Dejardin Olivier , Bouvier Véronique , Arveux Patrick , Maynadie Marc , Launoy Guy , Bouvier Anne‐Marie
Published: May 2016

Pancreatic survival is one of the worst in oncology. To what extent wait times affect outcomes in unknown No population‐based study has previously explored patient and treatment delays among individuals with pancreatic cancer. The aim of this study was to estimate patient and treatment delays in patients with pancreatic cancer and to measure their association with survival in a nonselected population. All patients diagnosed with pancreatic cancer for the first time between 2009 and 2011 and registered in two French digestive cancer registries were included. Patient delay (time from onset of symptoms until the first consultation categorized into <1 or ≥1 month), and treatment delay (time between the first consultation and treatment categorized into less or more than 29 days, the median time) were collected. Overall delay was used to test associations between survival and the timeliness of care by combining patient delay and treatment delay. Patient delay was longer than 1 month in 46% of patients. A patient delay longer than one month was associated with the absence of jaundice (p < 0.001) and the presence of metastasis (p = 0.003). After adjusting for other covariates, such as symptoms and treatment, the presence of metastasis was negatively associated with treatment delay longer than 29 days (p = 0.025). After adjustment for other covariates, especially metastatic dissemination and the result of the resection, overall delay was not significantly associated with prognosis. We found little evidence to suggest that timely care was associated with the survival of patients.
Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway
Authors: Yu Jiahui , Chen Yongyu , Fu Xiangsheng , Zhou Xian , Peng Yan , Shi Lei , Chen Ting , Wu Yaxin
Published: May 2016

The prevalence of invasive Fusobacterium nucleatum (Fn) within the serrated neoplasia pathway of the proximal colon has seldom been investigated. We examined the invasive Fn and bacterial biofilms in 35 proximal hyperplastic polyps (HPs), 33 sessile serrated adenomas (SSAs), 48 proximal colorectal cancers (CRCs) and 10 matched metastatic lymph nodes using 16S rRNA fluorescence in situ hybridization (FISH). Samples of normal mucosa, traditional adenomas (TAs), distal HPs, distal CRCs and matched lymph nodes with or without metastases were used as controls. The prevalence of invasive Fn within proximal HPs (65.7%) and SSAs (78.8%) were significantly higher than that of proximal TAs (28.9%) and distal TAs (24.4%; p < 0.05). Invasive Fn was detected in markedly more proximal CRCs (89.6%) than in distal CRCs (42.2%; p < 0.05). Moreover, invasive Fn was detected in a significantly higher proportion of matched metastatic lymph nodes (100%) than that within nonmetastatic lymph nodes (40.0%; p < 0.001). Bacterial biofilms were found on 52.1% of proximal CRCs, 55.6% of distal CRCs and 48.5% of SSAs. Biofilms were positive for Fn in 47.9% of proximal CRCs, 48.9% of distal CRCs and 27.3% of SSAs. However, the presence of Fn in biofilms was not related to invasive Fn within colorectal tissues (p = 0.415). Invasive Fn may play a role in the carcinogenesis of proximal colon developing via the serrated neoplasia pathway, but might have a less important role in the TA‐carcinoma sequence. Bacterial biofilms may not contribute to the invasion of Fn into tumor tissues.
Hydroxyapatite‐doped alginate beads as scaffolds for the osteoblastic differentiation of mesenchymal stem cells
Authors: Wang Martha O. , Bracaglia Laura , Thompson Joshua A. , Fisher John P.
Published: May 2016

This work investigates the role of an osteoblastic matrix component, hydroxyapatite (HA), in modular alginate scaffolds to support osteoblastic differentiation of human mesenchymal stem cells for the purpose of tissue engineered bone constructs. This system is first evaluated in a tubular perfusion bioreactor, which has been shown to improve osteoblastic differentiation over static culture conditions. HMSCs in alginate scaffolds that contain HA show increased osteoblastic gene expression compared to cells in pure alginate scaffolds, as well as significantly more matrix production and mineralization. The differentiated hMSCs and cell‐laid matrix are ultimately evaluated in an in vivo site specific model. Implantation of these scaffolds with preformed matrix into the rat femoral condyle defects results in abundant bone growth and significant incorporation of the scaffold into the surrounding tissue. The developed mineralized matrix, induced in part by the HA component in the scaffold, could lead to increased tissue development in critically sized defects, and should be included in future implant strategies. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2325–2333, 2016.
Anti‐Angiogenic Properties of Cafestol and Kahweol Palmitate Diterpene Esters
Authors: Moeenfard Marzieh , Cortez Alice , Machado Vera , Costa Raquel , Luís Carla , Coelho Pedro , Soares Raquel , Alves Arminda , Borges Nuno , Santos Alejandro
Published: May 2016

Epidemiological studies support the association of coffee‐specific diterpenes, with various beneficial health effects. Although anti‐antiangiogenic properties of free cafestol and kahweol have been recently described, available data regarding their esterified form, in particular palmitate esters as the main diterpene esters present in coffee, are still rare. Given that angiogenesis plays an important role in many pathological conditions, including cancer growth and metastasis, this study aimed to assess and compare the potential anti‐angiogenic effects of cafestol palmitate (CP) and kahweol palmitate (KP) in an in vitro angiogenesis model. According to our findings, both compounds inhibited angiogenesis steps on human microvascular endothelial cells (HMVECs), although a more significant effect was observed for KP. Compared to control, HMVECs viability decreased in a dose‐dependent manner upon incubation either with CP or KP. Concentrations of 75 and 100 μM of each compound were cytotoxic. Cell proliferation was also dramatically reduced by both diterpene esters at 50 μM, although KP had a stronger inhibitory effect. However, CP and KP did not induce apoptosis on HMVECs. Both compounds reduced cell migration, but this effect was only statistically significant after KP incubation. Inhibition of VEGFR2 expression and its downstream effector Akt, but not Erk, was also observed in CP‐ and KP‐treated HMVECs. These findings were confirmed using ELISA assay for phosphorylated (active) VEGFR‐2. Taken together, these data indicate that both CP and KP can be considered potent compounds against angiogenesis‐dependent disorders. Our findings further indicate that KP exerts more potent anti‐angiogenic effects than CP, in most of assays. J. Cell. Biochem. 117: 2748–2756, 2016. © 2016 Wiley Periodicals, Inc.
N‐Linked Glycosylation Is Required for Vacuolar H+‐ATPase (V‐ATPase) a4 Subunit Stability, Assembly, and Cell Surface Expression
Authors: Esmail Sally , Yao Yeqi , Kartner Norbert , Li Jing , Reithmeier Reinhart A. F. , Manolson Morris F.
Published: May 2016

The a subunit is the largest of 14 different subunits that make up the V‐ATPase complex. In mammalian species this membrane protein has four paralogous isoforms, a1–a4. Clinically, a subunit isoforms are implicated in diverse diseases; however, little is known about their structure and function. The subunit has conserved, predicted N‐glycosylation sites, and the a3 isoform has been directly shown to be N‐glycosylated. Here we ask if human a4 (ATP6V0A4) is N‐glycosylated at the predicted site, Asn489. We transfected HEK 293 cells, using the pCDNA3.1 expression‐vector system, to express cDNA constructs of epitope‐tagged human a4 subunit, with or without mutations to eliminate the putative glycosylation site. Glycosylation was characterized also by treatment with endoglycosidases; expression and localization were assessed by immunoblotting and immunofluorescence. Endoglycosidase‐treated wild type (WT) a4 showed increased relative mobility on immunoblots, compared with untreated WT a4. This relative mobility was identical to that of unglycosylated mutant a4N489D, demonstrating that the a4 subunit is glycosylated. Cycloheximide pulse‐chase experiments showed that the unglycosylated subunit degraded at a higher rate than the N‐glycosylated form. Unglycosylated a4 was degraded mostly in the proteasomal pathway, but also, in part, through the lysosomal pathway. Immunofluorescence colocalization data showed that unglycosylated a4 was mostly retained in the ER, and that plasma membrane trafficking was defective. Co‐immunoprecipitation studies suggested that a4N489D does not assemble with the V‐ATPase V1 domain. Taken together, these data show that N‐glycosylation plays a crucial role in a4 stability, and in V‐ATPase assembly and trafficking to the plasma membrane. J. Cell. Biochem. 117: 2757–2768, 2016. © 2016 Wiley Periodicals, Inc.
Necessity of high‐resolution for coarse‐grained modeling of flexible proteins
Authors: Jia Zhiguang , Chen Jianhan
Published: May 2016

The popular MARTINI coarse‐grained (CG) force field requires the protein structure to be fixed, and is unsuitable for simulating dynamic processes such as protein folding. Here, we examine the feasibility of developing a flexible protein model within the MARTINI framework. The results demonstrate that the MARTINI CG scheme does not properly describe the volume and packing of protein backbone and side chains and leads to excessive collapse without structural restraints in explicit CG water. Combining atomistic protein representation with the MARTINI CG solvent, such as in the PACE model, dramatically improves description of flexible protein conformations. Yet, the CG solvent is insufficient to capture the conformational dependence of protein–solvent interactions, and PACE is unable to properly model context dependent conformational transitions. Taken together, high physical resolution at or near the atomistic level is likely necessary for flexible protein models with explicit, microscopic solvents, and the coarse‐graining needs to focus on possible simplification in interaction potentials. © 2016 Wiley Periodicals, Inc.
Effects of NH4Br additive on mercury transformation and removal during CFB coal combustion
Authors: Zhao Shilin , Duan Yufeng , Zhou Qiang , Zhu Chun , Liu Meng , Lu Jianhong
Published: May 2016

BACKGROUND

Mercury emission from coal‐fired power plants has caused widespread concern. Halogen is considered to be a good mercury oxidant and many researchers have added it into the coal for mercury removal. However, the mechanism of mercury transformation is still not clear. Effects of NH4Br additive on mercury transformation and removal were studied on a 6 kWth circulating fluidized bed (CFB) coal combustor. The main goal of this work is to explore in detail the mercury transformation mechanism in the presence of bromine.

RESULTS

Results showed that the concentration of Hg0 and Hg2+ in the flue gas was 2.003 and 2.434 µg m−3, respectively, while Hgp was 14.866 µg m−3 during the raw coal combustion. By adding more NH4Br, the content of Hg0 and Hg2+ decreased while the content of Hgp increased. At an NH4Br addition amount of 0.3%, Hg0 transformation rate and Hgg removal rate reached maximum values of 78.85% and 76.83%, respectively. Some mercury compounds (such as HgS(red), HgO, HgSO3) were further oxidized by active bromine with NH4Br addition.

CONCLUSION

The added NH4Br generates active bromine in the furnace, which promotes both homogeneous and heterogeneous oxidation of mercury. Adding NH4Br into coal benefits mercury removal during coal combustion. © 2016 Society of Chemical Industry
Thermal pretreatment of microalgae for biomethane production: experimental studies, kinetics and energy analysis
Authors: Wang Meng , Lee Eunyoung , Dilbeck Merrill P , Liebelt Matthew , Zhang Qiong , Ergas Sarina J
Published: May 2016

BACKGROUND

Microalgae grown on wastewater are promising feedstocks for biomethane production by anaerobic digestion. However, the hemicellulose composition of the microalgae cell wall inhibits hydrolysis of intracellular substances and limits their anaerobic digestibility. This study investigated enhancement of biomethane production rates during anaerobic digestion of Chlorella sp. using thermal pretreatment at varying temperatures. Experimental data were fitted to three simplified kinetic models and an energy analysis was performed to gain insights into this potential application of thermal pretreatment.

RESULTS

Methane yields from untreated algae were 155 mL g−1 VSadd, while thermal pretreatment at 70 °C and 90 °C for 0.5 h increased the methane yield by 37% and 48%, respectively. Thermal pretreatment at 121 °C for 0.3 h resulted in the highest methane yield (322 mL g−1 VSadd), which is 108% higher than the untreated algae. Data from digestion of thermally pretreated microalgae were best described by a first‐order kinetic model. However, for untreated microalgae the Gompertz model, which includes a lag phase, provided the best fit to the methane production data.

CONCLUSIONS

Thermal pretreatment improved the maximum methane production rate and shortened the lag period during anaerobic digestion. However, the energy balance indicated that pretreatment of microalgae could not achieve a positive energy balance compared with anaerobic digestion of untreated microalgae. Co‐digestion with other biomass or increasing the solids concentration of anaerobic digestion could be used to increase the overall energy efficiency. © 2016 Society of Chemical Industry
Adhesion resistant chitosan coated iron oxide polyacrylonitrile mixed matrix membrane for disinfection of surface water
Authors: Mukherjee Munmun , Panda Swapna Rekha , De Sirshendu
Published: May 2016

BACKGROUND

Surface water possesses numerous microbial pathogens due to domestic disposal and poor sanitation. Most of the available conventional disinfection techniques are cost intensive and energy consuming. Being cost effective and environmentally friendly, membrane separation proves to be a better disinfection technology. However, fouling is the major challenge of this technology reducing its throughput. This study highlights preparation of fouling resistant chitosan coated iron oxide polyacrylonitrile (PAN) mixed matrix membrane (MMM) for disinfection of surface water.

RESULTS

In this work, antimicrobial and anti‐adhesive properties of MMM are explored for disinfection of pond water with high organic load. Significance of incorporating nanoparticles and a coating of chitosan on removal of microorganisms was investigated. Adsorption of Escherichia coli on MMM was quantified and confirmed by FTIR. Improved antimicrobial properties of MMM against Escherichia coli was evident by a wider halo zone (7 cm). Up to 99.9% removal efficiency of microorganisms was attained. The membrane permeability was restored by simple cleaning with distilled water.

CONCLUSION

The MMM developed not only exhibited strong antimicrobial efficiency but also showed significant anti‐adhesive property making it a suitable candidate for purification of surface water. © 2016 Society of Chemical Industry
Antipsychotic medication utilization in nonpsychiatric hospitalizations
Authors: Herzig Shoshana J. , Rothberg Michael B. , Guess Jamey R. , Gurwitz Jerry H. , Marcantonio Edward R.
Published: May 2016

BACKGROUND

Although antipsychotics are used for treatment of delirium/agitation in hospitalized patients, their scope of use has not been investigated in a large, multicenter cohort.

OBJECTIVE

To determine rates of use and hospital variation in use of antipsychotics in nonpsychiatric admissions.

DESIGN, SETTING, PATIENTS

Cohort study of adult, nonpsychiatric admissions to 300 US hospitals contributing data to the Premier database, from July 1, 2009 to June 30, 2010.

MEASUREMENTS

Antipsychotic exposure defined using pharmacy charges. Potentially excessive dosing defined using guidelines for long‐term care facilities.

RESULTS

Our cohort included 2,695,081 admissions (median age, 63 years; 56% female). Antipsychotic exposure occurred in 160,773 (6%) admissions; 102,148 (64%) received atypical antipsychotics, 76,979 (48%) received typical, and 18,354 (11%) received both. Among exposed admissions, 47% received ≥1 potentially excessive daily dose. Among the variables we analyzed, the strongest predictors of antipsychotic receipt were delirium (relative risk [RR]: 2.93, 95% CI: 2.88‐2.98) and dementia (RR: 2.78, 95% CI: 2.72‐2.83). After adjustment for patient characteristics, patients admitted to hospitals in the highest antipsychotic prescribing quintile were more than twice as likely to be exposed compared to patients admitted to hospitals in the lowest prescribing quintile (RR: 2.56, 95% CI: 2.50‐2.61). This relationship was similar across subgroups of admissions with delirium and dementia.

CONCLUSIONS

Antipsychotic medication exposure is common in nonpsychiatric admissions to US hospitals. The observed variation in antipsychotic prescribing was not fully explained by measured patient characteristics, suggesting the possibility of differing hospital prescribing cultures. Additional research and guidelines are necessary to define appropriate use of these potentially harmful medications in the hospital setting. Journal of Hospital Medicine 2016;11:543–549. © 2016 Society of Hospital Medicine
Engaging hospitalists in antimicrobial stewardship: Lessons from a multihospital collaborative
Authors: Mack Megan R. , Rohde Jeffrey M. , Jacobsen Diane , Barron James R. , Ko Christin , Goonewardene Michael , Rosenberg David J. , Srinivasan Arjun , Flanders Scott A.
Published: May 2016

Inappropriate antimicrobial use in hospitalized patients contributes to antimicrobial‐resistant infections and complications. We sought to evaluate the impact, barriers, and facilitators of antimicrobial stewardship best practices in a diverse group of hospital medicine programs. This multihospital initiative included 1 community nonteaching hospital, 2 community teaching hospitals, and 2 academic medical centers participating in a collaborative with the Centers for Disease Control and Prevention and the Institute for Healthcare Improvement. We conducted multimodal physician education on best practices for antimicrobial use including: (1) enhanced antimicrobial documentation, (2) improved quality and accessibility of local clinical guidelines, and (3) a 72‐hour antimicrobial “timeout.” Implementation barriers included variability in physician practice styles, lack of awareness of stewardship importance, and overly broad interventions. Facilitators included engaging hospitalists, collecting real time data and providing performance feedback, and appropriately limiting the scope of interventions. In 2 hospitals, complete antimicrobial documentation in sampled medical records improved significantly (4% to 51% and 8% to 65%, P < 0.001 for each comparison). A total of 726 antimicrobial timeouts occurred at 4 hospitals, and 30% resulted in optimization or discontinuation of antimicrobials. With careful attention to key barriers and facilitators, hospitalists can successfully implement effective antimicrobial stewardship practices. Journal of Hospital Medicine 2016;11:576–580. © 2016 Society of Hospital Medicine
How well do patients and providers agree on the severity of dyspnea?
Authors: Stefan Mihaela S. , Priya Aruna , Martin Benjamin , Pekow Penelope S. , Rothberg Michael B. , Goldberg Robert J. , DiNino Ernest , Lindenauer Peter K.
Published: May 2016

BACKGROUND

Understanding the severity of patients' dyspnea is critical to avoid under‐ or overtreatment of patients with acute cardiopulmonary conditions.

OBJECTIVE

To evaluate the agreement between dyspnea assessment by patients and healthcare providers and to explore which factors contribute to discordance in assessment.

DESIGN, SETTINGS AND PARTICIPANTS

Prospective study of patients hospitalized for acute cardiopulmonary diseases at an urban teaching hospital.

INTERVENTION AND MEASUREMENTS

A numerical rating scale (0–10) was used to assess dyspnea severity as perceived by patients and assessed by providers. Agreement was defined as a score within ±1 between patient and healthcare provider; differences of ≥2 points were considered over‐ or underestimations. The relationship between patient self‐perceived dyspnea severity and provider rating was assessed using a weighted kappa coefficient.

RESULTS

Of the 138 patients enrolled, 33% had a diagnosis of heart failure, 30% chronic obstructive pulmonary disease, and 13% pneumonia; median age was 72 years, and 57% were women. In all, 96 patient‐physician and 138 patient‐nurses pairs were included in the study. The kappa coefficient for agreement was 0.11 (95% confidence interval [CI]: 0.01 to 0.21) between patients and physicians and 0.18 (95% CI: 0.12 to 0.24) between patients and nurses. Physicians underestimated patients' dyspnea 37.9% of the time and overestimated it 25.8% of the time, whereas nurses underestimated it 43.5% of the time and overestimated it 12.4% of the time. Admitting diagnosis was the only patient factor associated with discordance.

CONCLUSIONS

Agreement between patient perception of dyspnea and healthcare providers' assessment is low. Future studies should prospectively test whether routine assessment of dyspnea results in better patient outcomes. Journal of Hospital Medicine 2016;11:701–707. © 2016 Society of Hospital Medicine
Dietary correlates associated with the mental foramen in primates: implications for interpreting the fossil record
Authors: Muchlinski Magdalena N. , Deane Andrew S.
Published: May 2016

The mandibular nerve is a sensory and motor nerve that innervates the muscles of mastication, the lower dentition, and the lower lip and surrounding structures. Although this nerve contains both efferent and afferent fibers, the mental nerve, a terminal branch of the mandibular nerve, is a strictly sensory nerve that exits the mental foramen and innervates the lower lip, the skin overlaying the mandible, and the oral mucosa around the mandible. Osteological foramina are often used as proxies for nerve cross section area and they often correlate well with some aspect of a primate's ecology (e.g., optic foramen and visual acuity). The primary objective of this study is to explore the correlation between the mental foramen and dietary preference among primates. The mental foramen of 40 primate species (n = 180) was measured from 3‐D surface models of the mandible. Both conventional and phylogenetic tests indicate that although frugivores have larger mental foramina than folivores, the differences were not significant. These results show that while structures like the infraorbital foramen correlate well with diet and touch sensitivity, the mental foramen does not. Based on these findings, the mental foramen is not a suggested morphological character for interpreting of the fossil record. J. Morphol. 277:978–985, 2016. © 2016 Wiley Periodicals, Inc.