bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon signature in patients with STAT1 gain‐of‐function mutation is epigenetically determined
Authors: Kaleviste Epp , Saare Mario , Leahy Timothy Ronan , Bondet Vincent , Duffy Darragh , Mogensen Trine H. , Jørgensen Sofie E , Nurm Helke , Ip Winnie , Davies E Graham , Sauer Sascha , Syvänen Ann‐Christine , Milani Lili , Peterson Pärt , Kisand Kai
Published: February 2019

STAT1 gain‐of‐function (GOF) variants lead to defective Th17 cell development and chronic mucocutaneous candidiasis (CMC), but frequently also to autoimmunity. Stimulation of cells with STAT1 inducing cytokines like interferons (IFN) result in hyperphosphorylation and delayed dephosphorylation of GOF STAT1. However, the mechanism how the delayed dephosphorylation exactly causes the increased expression of STAT1‐dependent genes, and how the intracellular signal transduction from cytokine receptors is affected, remains unknown. In this study we show that the circulating levels of IFN‐α were not persistently elevated in STAT1 GOF patients. Nevertheless, the expression of interferon signature genes was evident even in the patient with low or undetectable serum IFN‐α levels. Chromatin immunoprecipitation (ChIP) experiments revealed that the active chromatin mark trimethylation of lysine 4 of histone 3 (H3K4me3), was significantly enriched in areas associated with interferon‐stimulated genes in STAT1 GOF cells in comparison to cells from healthy donors. This suggests that the chromatin binding of GOF STAT1 variant promotes epigenetic changes compatible with higher gene expression and elevated reactivity to type I interferons, and possibly predisposes for interferon‐related autoimmunity. The results also suggest that epigenetic rewiring may be responsible for treatment failure of Janus kinase 1/2 (JAK1/2) inhibitors in certain patients.
Cyclometalated Ruthenium(II) NHC Complexes with Imidazo[1,5‐a]pyridine‐Based (C^C*) Ligands – Synthesis and Characterization
Authors: Schleicher David , Tronnier Alexander , Soellner Johannes , Strassner Thomas
Published: February 2019

We present the synthesis and characterization of cyclometalated ruthenium(II) NHC complexes with phenyl‐substituted imidazo[1,5‐a]pyridine C^C* ligands. The corresponding p‐cymene complexes can be reacted with bipyridine to form bisheteroleptic ruthenium(II) dyes. The compounds have been characterized by one‐ and two‐dimensional 1H/13C NMR spectroscopy, elemental analysis, cyclic voltammetry, infrared spectroscopy, as well as solid‐state structure (X‐ray) analysis.
Asymmetric Synthesis of Saturated Hydroxy Fatty Acids and Fatty Acid Esters of Hydroxy Fatty Acids
Authors: Mountanea Olga G. , Limnios Dimitris , Kokotou Maroula G. , Bourboula Asimina , Kokotos George
Published: February 2019

The recent discovery of a novel class of endogenous lipids, named Fatty Acid esters of Hydroxy Fatty Acids (FAHFAs), that present antidiabetic and anti‐inflammatory activities, has attracted the interest on hydroxy fatty acids (HFAs) and their derivatives. We present herein the development of a convenient and general methodology for the asymmetric synthesis of HFAs and FAHFAs. The enantioselective organocatalytic synthesis of asymmetric terminal epoxides starting from monoprotected α,ω‐diols and their subsequent ring opening by a Grignard reagent are the key‐steps for our methodology, allowing the introduction of the hydroxy group at different positions of the long chain by proper selection of the starting diol and the Grignard reagent. MacMillan's third generation imidazolidinone organocatalyst has been employed for the epoxide formation, ensuring products in high enantiomeric purity. Furthermore, an approach for the synthesis of deuterated HFAs and FAHFAs was developed, leading to deuterated derivatives, which can be useful in biological studies and in mass spectrometry studies as internal standards.
Coloration, UV Protective, and Antioxidant Finishing of Wool Fabric Via Natural Dye Extracts: Cleaner Production of Bioactive Textiles
Authors: Rather Luqman Jameel , Shabbir Mohd , Li Qing , Mohammad Faqeer
Published: February 2019

Biocompatibility and biodegradability of natural compounds attracted researchers to utilize them toward healthy environment, and so for the production of ecofriendly textiles. The present study reports a cleaner production approach to develop bioactive textiles via the application of Acacia nilotica, Terminalia arjuna, and Adhatoda vasica natural dyes. Colorimetric characteristics, sun protection and antioxidant properties of bioactive wool fabrics have been evaluated. Evaluation of these characteristics with the effect of iron pre‐mordanting was also assessed. A broad range color palette is obtained with good fastness results to washing and rubbing. Sun protection properties of developed bioactive wool fabrics were assessed in terms of ultraviolet protection factor (UPF) and UV transmittance in ultra‐violet region (UV‐A and UV‐B), relative to un‐dyed wool fabrics. Antioxidant properties of developed wool fabric were determined in terms of % inhibition of peroxidation by ABTS (2,2′‐Azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid)) radical scavenging activity. Transmittance values of <5% and >40% inhibition of peroxidation demonstrates the use of promising natural multifunctional finishing agents from A. nilotica, T. arjuna, and A. vasica natural dyes for the development of bioactive textile fabrics. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13146, 2019
Silicon PV module fitting equations based on experimental measurements
Authors: Sabry Ahmad H. , Hasan Wan Z. W. , Sabri Yasameen H. , Ab‐Kadir Mohd Zainal Abidin
Published: February 2019

Solar photovoltaic (PV) characteristic curves (P‐V and I‐V) offer the information required to configure the PV system to operate as near to its optimal performance as possible. Measurement‐based modeling can provide an accurate description for this purpose. This work analyzes the PV module performance and develops a mathematical formula under particular weather conditions to accurately express these curves based on a custom neural network (CNN). The study initially presents several standard mathematical model equations, such as polynomial, exponential, and Gaussian models to fit the PV module measurements. The model selection is subjected to the minimum value of an evaluation parameter. To simplify the solution of the symbolic equations for the CNN network, two neurons in the hidden layer with nonlinear activation function and linear for the output layer were selected. The results show the effectiveness of the proposed CNN model equations over other standard fitting models according to the root mean squared error (RMSE) evaluation. This method promises further improved results with multi‐input parameter modeling.
Insights into fuel start‐up and self‐sufficiency for fusion energy: The case of CFETR
Authors: Nie Baojie , Ran Guangming , Zeng Qin , Du Hongfei , Li Zaixin , Chen Yanjing , Zhu Zuolong , Zhao Xueli , Ni Muyi , Li Fengchen
Published: February 2019

Commercial tritium resources available are too scarce to fully supply the future fusion reactors after International Thermonuclear Experimental Reactor (ITER). Tritium self‐sufficiency, ITER fails to fully validate, was regarded as one of the most important issues needed to be solved in the pathway of achieving fusion energy. After ITER, several concepts of fusion engineering test reactors and fusion demonstration reactors have been proposed worldwide, for example, Chinese Fusion Engineering Test Reactor (CFETR), Fusion Nuclear Science Facility (FNSF), DEMOnstration fusion reactor (DEMO) in European Union and Korea. CFETR is in the engineering design phase and would be hopefully completed around 2020. Tritium resources for the reactor start‐up and tritium self‐sufficiency are two primary issues besides the steady‐state operation for CFETR. The objectives of this work are as follows: (a) to introduce the preliminary fuel cycle concept and available tritium resources for CFETR, (b) to evaluate and discuss the tritium demand for CFETR start‐up (phase I: 200 MW) and the feasibility of DD start‐up, (c) to identify the possible pathways to tritium self‐sufficiency through sensitivity analysis based on the design baseline of CFETR, (d) to evaluate the consequences in case of failing tritium self‐sufficiency, and (e) to identify future R&D needed for tritium self‐sufficiency. It is expected to give insights into the question on how to start the reactor in a more economical way, into the feasibility of tritium self‐sufficiency, and into the question on what will happen in case of failing tritium self‐sufficiency.
A Bayesian structural model for predicting algal blooms
Authors: Sun Xinyu , Liu Tao , Wang Jiayin
Published: February 2019

A Bayesian structural model with two components is proposed to forecast the occurrence of algal blooms, multivariate mean‐reverting diffusion process (MMRD), and a binary probit model with latent Markov regime‐switching process (BPMRS). The model has three features: (a) forecast of the occurrence probability of algal bloom is directly based on oceanographic parameters, not the forecasting of special indicators in traditional approaches, such as phytoplankton or chlorophyll‐a; (b) augmentation of daily oceanographic parameters from the data collected every 2 weeks is based on MMRD. The proposed method solves the problem of unavailability of daily oceanographic parameters in practice; (c) BPMRS captures the unobservable factors which affect algal bloom occurrence and therefore improve forecast accuracy. We use panel data collected in Tolo Harbour, Hong Kong, to validate the model. The model demonstrates good forecasting for out‐of‐sample rolling forecasts, especially for algal bloom appearing for a longer period, which severely damages fisheries and the marine environment.
Palaeoarchaean sedimentation and magmatic processes in the eastern Iron Ore Group, eastern India: A commentary
Authors: Mazumder Rajat , Chaudhuri Trisrota , Biswas Sayan
Published: February 2019

The Singhbhum cratonic block, eastern India, unlike other Indian cratonic blocks, bears a continuous geological record from the Palaeoarchaean to Mesoproterozoic. The Palaeoarchaean Iron Ore Group of rocks are exposed along three distinct belts (the eastern, western, and southern) encircling the Singhbhum granitoids. The economic geological aspects of the BIF and the gold mineralization aspects of the quartz‐pebble conglomerates of the Eastern Iron Ore Group (EIOG) have been discussed by a number of authors. Komatiites and basalts of the EIOG have been studied by earlier authors. However, no effort has yet been made to infer the volcano‐sedimentary processes in the Eastern Iron Ore belt. This paper presents a brief overview of the sedimentation and magmatic processes in the EIOG belt. The EIOG sedimentary succession is characterized by a basal terrestrial to shallow marine deposits that progressively became deeper up section. The EIOG clastics bear carbonaceous matter. The basal terrestrial deposits (conglomerate‐sandstone association) of the EIOG provide a rare opportunity to undertake fluvial architectural analysis and may enable us to unlock the peculiarities of Palaeoarchaean fluvial systems.
Gi/o protein‐coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission
Authors: Durkee Caitlin A. , Covelo Ana , Lines Justin , Kofuji Paulo , Aguilar Juan , Araque Alfonso
Published: February 2019

G protein‐coupled receptors (GPCRs) play key roles in intercellular signaling in the brain. Their effects on cellular function have been largely studied in neurons, but their functional consequences on astrocytes are less known. Using both endogenous and chemogenetic approaches with DREADDs, we have investigated the effects of Gq and Gi/o GPCR activation on astroglial Ca2+‐based activity, gliotransmitter release, and the functional consequences on neuronal electrical activity. We found that while GqGPCR activation led to cellular activation in both neurons and astrocytes, Gi/oGPCR activation led to cellular inhibition in neurons and cellular activation in astrocytes. Astroglial activation by either Gq or Gi/o protein‐mediated signaling stimulated gliotransmitter release, which increased neuronal excitability. Additionally, activation of Gq and Gi/o DREADDs in vivo increased astrocyte Ca2+ activity and modified neuronal network electrical activity. Present results reveal additional complexity of the signaling consequences of excitatory and inhibitory neurotransmitters in astroglia‐neuron network operation and brain function.
IRB Becomes E&HR
Authors: Kaebnick Gregory E.
Published: February 2019

In January 2019, under the new name Ethics & Human Research, The Hastings Center relaunched its forty‐year‐old journal that focuses on the ethical, regulatory, and policy issues related to research with humans. Formerly called IRB: Ethics & Human Research, E&HR has the same editorial team, led by the Hastings scholar Karen Maschke, and is meant to continue the work of IRB but will also feature a greater range of scholarship on issues in science and health care that have implications for research with humans. While E&HR is formally a continuation of IRB, it feels like a new journal. It is similar in design and format to its sister journal, the Hastings Center Report, and it has a closely linked channel for publication and distribution. Like HCR, it is published through John Wiley & Sons in both paper and electronic formats. Its home on the Wiley Online Library is https://onlinelibrary.wiley.com/journal/25782363.
Editorial Trends
Authors: Kaebnick Gregory E.
Published: February 2019

I was recently asked to report on editorial trends in the Hastings Center Report, past and future. What I reported is that HCR has been going in two seemingly contrasting directions. One has to do with moral decision‐making in clinical ethics—the core theme in bioethics for fifty years, but still developing. A second editorial trend is treatment of larger social and political issues that bear on health, such as public health interventions and access to health care. I could also have noted a continuing stream of pieces on emerging technologies, from whole‐genome screening for newborns to artificial intelligence in clinical diagnoses to the so‐called de‐extinction of extinct animals and plants through various genetic and reproductive tricks. This January‐February 2019 issue of HCR reflects all these trends.
North of Home: Obligations to Families of Undocumented Patients
Authors: Fins Joseph J. , Real de Asúa Diego
Published: February 2019

Undocumented and undomiciled, Gustavo Jiménez had been in the United States for several years. He knew his leg wasn’t right when it began to swell and redden. After the cellulitis spread to his bloodstream, he was found unconscious on the street and admitted to the intensive care unit. He improved quickly and was soon able to tell a social worker his name and that he had family in Quito. Then his health took a turn for the worse, and he developed multisystem organ failure. His doctors believed his prognosis grave and further care futile. They wanted to invoke a provision under their state’s law that allows, at the discretion of at least two physicians, for the withdrawal of life‐sustaining therapy for isolated and decisionally incapacitated patients, but the social worker had ethical concerns about the doctors’ desire to make such a momentous decision without family input. She asked for a “time‐out to locate his family,” but one of the doctors asserted, “His family isn’t here, and you’ll never find them. Besides we need the bed. The ER is full of patients we can help.” What is owed a patient and family in such a situation?
An Ethical Obligation for Bioethicists to Utilize Social Media
Authors: Herron Patrick D.
Published: February 2019

In this issue of the Hastings Center Report, Mélanie Terrasse, Moti Gorin, and Dominic Sisti respond to recent efforts to address the “digital attention crisis,” arguing that “[b]ioethicists should make their voices heard in the debate on the responsibilities of social media companies toward their consumers and society at large.” I strongly agree. I have frequently been asked by my colleagues why I spend time on social media professionally, on top of all the competing demands associated with my work as a bioethicist and medical educator. There is sometimes a dismissive tone in these questions, a sense that attention to social media is beneath a bioethicist’s proper intellectual pursuits. Such perspectives overlook the extraordinary opportunities of social media and the important role for bioethics, as a field, in examining them.
Expression of Metastatic Tumor Antigen 1 Splice Variant Correlates With Early Recurrence and Aggressive Features of Hepatitis B Virus–Associated Hepatocellular Carcinoma
Authors: Li Yung‐Tsung , Wu Hui‐Lin , Kao Jia‐Horng , Cheng Huei‐Ru , Ho Ming‐Chih , Wang Chih‐Chiang , Chen Pei‐Jer , Chen Ding‐Shinn , Liu Chun‐Jen
Published: February 2019

Overexpression of metastatic tumor antigen 1 (MTA1) was correlated with poor prognosis of hepatitis B virus (HBV)‐associated hepatocellular carcinoma (HBV‐HCC). The aim of this study was to examine the clinical significance of the expression of MTA1 and its exon 4‐excluded form (MTA1dE4), the most abundant spliced variant of MTA1, in patients receiving curative resection for HBV‐HCC. We collected 102 patients with HBV‐HCC and received curative resection retrospectively and examined the expressions level of total MTA1/MTA1dE4 in their paired nontumor and tumor liver tissues by using RT‐qPCR. The association between MTA1/MTA1dE4 expression and various tumor features as well as tumor recurrence was analyzed. During the median follow‐up period of 4 years, 25 patients (24.5%) showed early recurrence (within 12 months postresection) and 42 (54.5%) showed late recurrence. In Kaplan‐Meier analysis, MTA1dE4 overexpression in tumor, but not MTA1, was associated with early recurrence (P = 0.0365), but not late recurrence. In multivariate analysis, only alpha‐fetoprotein (AFP) ≥200 ng/mL (P = 0.006) and large tumor size (P = 0.027) were correlated with early recurrence. In the subgroup of patients with AFP <200 ng/mL, high MTA1dE4, but not total MTA1, expression could help predict early recurrence (P = 0.0195). In vitro, wound healing and invasion assays were performed in HCC cells, and MTA1dE4 was found to exhibit a higher ability in promoting migration and invasion of hepatoma cells than full‐length MTA1. Conclusion: MTA1dE4 expression is correlated with more aggressive tumor characteristics and might serve as a more sensitive marker for early recurrence of HBV‐HCC, especially for low‐AFP patients.
Hamilton Receptor‐Mediated Self‐Assembly of Orthogonally Functionalized Au and TiO2 Nanoparticles
Authors: Ali Muhammad , Hasenöhrl Dominik H. , Zeininger Lukas , Müllner Alexander R. M. , Peterlik Herwig , Hirsch Andreas
Published: February 2019

A new prototype of reversible self‐assembly between functionalized gold and titanium dioxide nanoparticles (NPs) utilizing hydrogen bonding interactions was developed and established. The gold nanoparticles were functionalized with a Hamilton‐receptor functionality bearing a thiol moiety as anchoring group. The titanium dioxide nanoparticles were modified with cyanurate derivatives which contained phosphonic acids as anchoring groups. The host–guest type interaction between two functionalized nanoparticles yielded a highly integrated nanoparticle system in chloroform. Moreover, by presenting a competing ligand in an exchange reaction, the product of self‐assembly can be segregated into the individual soluble components of functionalized nanoparticles. The self‐assembly and the exchange reaction were followed and monitored in detail by UV/Vis spectroscopy. The structure of the self‐assembly product was investigated using scanning electron microscopy (SEM) and small‐angle X‐ray scattering (SAXS).
Temporal analysis of dual phase‐lag double‐diffusive MHD flow within a porous microchannel with chemical reaction
Authors: Endalew Mehari Fentahun , Sarkar Subharthi
Published: February 2019

A novel investigation is carried out to capture the transient effects of a dual phase‐lag (DPL) model for combined heat and mass transfer magnetohydrodynamic (MHD) flow within a porous microchannel in the presence of Dufour effects and homogenous first‐order chemical reaction. The governing equations for the fluid flow problem are solved using the Laplace transform method, which is a powerful technique for solving partial differential equations. Its inversion is done by using the INVLAP subroutine of MATLAB. The numerical values of fluid velocity, fluid temperature, and species concentration are demonstrated graphically and those of skin friction, heat transfer rate, and mass transfer rate are presented through tables. It is for the first time that the actual time gap between the DPL model, the Cattaneo‐Vernotte model, and the classical Fourierʼs model has been deciphered and the results unique to the DPL model are presented. We observe a clear difference between the DPL and the other two models at a dimensionless time , which gradually diminishes as time progresses, and all models coincide together at , that is, where a steady state temperature is reached. An important contribution of this study lies in discovering the time‐bound effects of the phase‐lag parameters of the DPL model on fluid temperature, species concentration, and fluid velocity and support them by physical justification. A similar discussion is provided for all other flow parameters. The results conveyed through this study would undoubtedly help researchers to advance the design of mechanical systems in microdevices involving MHD flow in porous media.
Imaging and radiation of laminar jet diffusion flames with low coflow air velocity in microgravity
Authors: Zhang Dan , Li Sen
Published: February 2019

We present imaging results and radiation measurements from laminar jet diffusion flames burning in coflowing air conditions. Color and pseudocolor flames are obtained and used to analyze flame brightness and shape, which show that flames under normal gravity are brighter than in microgravity. The longer residence times for microgravity flames result in increased radiative loss, which leads to local extinction and low temperature at the flame tip. Flame radiation fractions for microgravity flames are larger than those in normal gravity for C2H
4 and CH
4. The velocity of coflowing air has a much more pronounced effect on radiation from microgravity flames compared to those in normal gravity. The radiation fractions from ethylene‐fueled flames in microgravity are large, leading to local extinction at the flame tip. We also analyzed the flame radiation fraction.
Understanding subgrid variability of snow depth at 1‐km scale using Lidar measurements
Authors: He Siwei , Ohara Noriaki , Miller Scott N.
Published: February 2019

It is well known that snow plays an important role in land surface energy balance; however, modelling the subgrid variability of snow is still a challenge in large‐scale hydrological and land surface models. High‐resolution snow depth data and statistical methods can reveal some characteristics of the subgrid variability of snow depth, which can be useful in developing models for representing such subgrid variability. In this study, snow depth was measured by airborne Lidar at 0.5‐m resolution over two mountainous areas in south‐western Wyoming, Snowy Range and Laramie Range. To characterize subgrid snow depth spatial distribution, measured snow depth data of these two areas were meshed into 284 grids of 1‐km × 1‐km. Also, nine representative grids of 1‐km × 1‐km were selected for detailed analyses on the geostatistical structure and probability density function of snow depth. It was verified that land cover is one of the important factors controlling spatial variability of snow depth at the 1‐km scale. Probability density functions of snow depth tend to be Gaussian distributions in the forest areas. However, they are eventually skewed as non‐Gaussian distribution, largely due to the no‐snow areas effect, mainly caused by snow redistribution and snow melt. Our findings show the characteristics of subgrid variability of snow depth and clarify the potential factors that need to be considered in modelling subgrid variability of snow depth.
Possible soil tension controls on the isotopic equilibrium fractionation factor for evaporation from soil
Authors: Gaj Marcel , McDonnell Jeffrey J.
Published: February 2019

The stable isotopes of hydrogen and oxygen (δ2H and δ18O) are useful conservative tracers for tracking the movement of water in soil. But although the tracking of water infiltrating through the soil profile and its movement as run‐off and groundwater recharge are well developed, water movement through the soil can also include evaporative fractionation. Soil water fractionation factors have, until now, been largely empirical. Unlike open water evaporation where temperature, humidity, and vapour pressure gradient define fractionation, soil water evaporation includes fractionation by soil matrix effects. These effects are still poorly characterized. Here, we present preliminary results from a simple laboratory experiment with four soil admixtures with grain sizes that range from sand to silt and clay. Our results show that soil tension seems to control the isotope fractionation of resident soil water. The relationship between soil tension and equilibrium fractionation appears to be independent of soil texture and appears well supported by thermodynamic theory. Although these results are preliminary, they suggest that future work should go after soil tension effects as a possible explanatory factor of soil water and water vapour fractionation.
Trends in cause of death among patients with multiple myeloma in Puerto Rico and the United States SEER population, 1987–2013
Authors: Castañeda‐Avila Maira A. , Ortiz‐Ortiz Karen J. , Torres‐Cintrón Carlos R. , Birmann Brenda M. , Epstein Mara M.
Published: February 2019

Multiple myeloma (MM) survival has improved due to recent developments in MM treatment. As a result, other co‐morbid conditions may be of increasing importance to MM patients’ long‐term survival. This study examines trends in common causes of death among patients with MM in Puerto Rico, and in the US Surveillance, Epidemiology, and End Results (SEER) population. We analyzed the primary cause of death among incident MM cases recorded in the Puerto Rico Central Cancer Registry (n = 3,018) and the US SEER Program (n = 67,733) between 1987 and 2013. We calculated the cumulative incidence of death due to the eight most common causes and analyzed temporal trends in mortality rates using joinpoint regression. Analyses of SEER were also stratified by Hispanic ethnicity. MM accounted for approximately 72% of all reported deaths among persons diagnosed with MM in Puerto Rico and in SEER. In both populations, the proportion of patients who died from MM decreased with increasing time since diagnosis. Age‐standardized temporal trends showed a decreased MM‐specific mortality rate among US SEER (annual percent change [APC] = −5.0) and Puerto Rican (APC = −1.8) patients during the study period, and particularly after 2003 in non‐Hispanic SEER patients. Temporal decline in non‐MM causes of death was also observed among US SEER (APC = −2.1) and Puerto Rican (APC = −0.1) populations. MM‐specific mortality decreased, yet remained the predominant cause of death for individuals diagnosed with MM over a 26‐year period. The most pronounced decreases in MM‐specific death occurred after 2003, which suggests a possible influence of more recently developed MM therapies.
CUL7 promotes cancer cell survival through promoting Caspase‐8 ubiquitination
Authors: Kong Yanjie , Wang Zehua , Huang Maobo , Zhou Zhongmei , Li Yi , Miao Huilai , Wan Xing , Huang Jian , Mao Xiaoyun , Chen Ceshi
Published: February 2019

The Cullin 7 (CUL7) gene encodes a member of the cullin family of E3 ubiquitin ligases. Accumulated evidence suggests that CUL7 is oncogenic. However, the mechanism by which CUL7 improves cancer cell survival has not been fully elucidated. Here, we reported that CUL7 confers anti‐apoptotic functions by interacting with Caspase‐8. CUL7 prevents Caspase‐8 activation by promoting Caspase‐8 modification with non‐degradative polyubiquitin chains at K215. CUL7 knockdown sensitized cancer cells to TRAIL‐induced apoptosis in vitro and in nude mice. These results suggest that CUL7 limits extrinsic apoptotic signaling by promoting Caspase‐8 ubiquitination.
Comparison of transvaginal repair versus laparoscopic repair of lower‐segment cesarean scar defects
Authors: Zhang Duoduo , Liang Shuo , Zhu Lan
Published: February 2019

Objective

To evaluate transvaginal repair versus laparoscopic repair of cesarean scar defects (CSDs).

Methods

A retrospective cohort study was conducted among 67 symptomatic women with CSDs who attended a tertiary hospital in Beijing, China, between July 1, 2013, and March 31, 2017. The participants underwent either transvaginal repair (n=31) or laparoscopic repair (n=36). Medical costs, perioperative outcomes, and surgical outcomes were compared.

Results

No statistically significant between‐group differences were found at baseline. The mean thickness of the residual myometrium increased from 1.71 ± 0.67 mm before surgery to 4.41 ± 2.09 mm after surgery in the transvaginal repair group (P<0.001), and from 1.81 ± 0.93 to 4.68 ± 1.96 mm in the laparoscopic repair group (P<0.001). The duration of menses after surgery was less than 10 days in both the transvaginal repair group (n=30, 96.3%) and the laparoscopic repair group (n=30, 83.9%; P=0.113). Operative time and medical costs were both lower in the transvaginal repair group than in the laparoscopic repair group (P<0.001). Conception rates for the two groups were similar among women who desired fertility.

Conclusion

Transvaginal repair of CSD was associated with reduced operative times and medical costs when compared with laparoscopic repair.
Gaussian probability bi‐histogram equalization for enhancement of the pathological features in medical images
Authors: Kuo Chung‐Feng Jeffrey , Wu Han‐Cheng
Published: February 2019

In order to enhance the pathological features of medical images and aid the medical diagnosis, the image enhancement is a necessary process. This study presented the Gaussian probability model combining with bi‐histogram equalization to enhance the contrast of pathological features in medical images. There are five different bi‐histogram equalizations, namely, bi‐histogram equalization (BBHE), dualistic sub‐image histogram equalization (DSIHE), bi‐histogram equalization with a plateau limit (BHEPL), bi‐histogram equalization median plateau limit (BHEPL‐D), and bi‐histogram equalization with modified histogram bins (BHEMHB). The entropy, contrast, absolute mean brightness error (AMBE), and skewness difference are used to quantize the enhancement results. From the experimental result, it is observed that the entropy and contrast of the images can be effectively enhanced by using Gaussian probability bi‐histogram equalizations, and the Gaussian probability bi‐histogram equalization median plateau limit (GPBHEPL‐D) has the best enhanced result. The proposed GPBHEPL‐D method is effective in strengthening the pathological features in medical images, so as to increase the efficiency of doctors' diagnoses and computer‐aided detection.
Assessment of dose capping in phenytoin loading practices in the emergency department and the impact of an emergency medicine pharmacist
Authors: Holder Martina C. , Bailey Abby M. , Baum Regan A. , Justice Stephanie B. , Weant Kyle A.
Published: February 2019

Objectives

Phenytoin is a common anticonvulsant used for the acute treatment of seizures in the emergency department (ED). Certain patient populations, such as the obese, have been shown to present dosing challenges. Often doses are arbitrarily “capped” for fear of overdosing. Emergency medicine pharmacists (EPhs) have been shown to optimize the care of patients receiving phenytoin therapy in other settings, demonstrating reductions in seizure activity, duration of therapy, and cost.

Methods

Records of patients presenting to the ED that were at least 18 years old and were prescribed intravenous phenytoin were reviewed. Patients weighing 100 kg or more were compared with those less than 100 kg. To evaluate the impact of an EPh, intravenous phenytoin orders placed during the EPh's hours were compared with those placed outside of those hours.

Results

A total of 117 patients were included, 42 (36%) weighed 100 kg or more. No significant difference was found in the achievement of target (10‐20 μg/mL) postload concentrations between the two groups (P = 0.795). Patients weighing 100 kg or more received significantly lower weight‐based phenytoin doses (16.0 vs 18.6 mg/kg, P = 0.0001). Those 100 kg or more who received less than 15 mg/kg were found to have significantly lower postload concentrations than those that received 15 mg/kg or more regardless of total dose (11.5 vs 16.5 μg/mL; P = 0.003). The presence of an EPh was found to result in significantly higher rates of postload concentrations within the therapeutic range across all groups (72.4% vs 53.7%; P = 0.04).

Conclusions

The available data suggest that artificial total dose limitations in patients yield significantly lower postload concentrations, potentially delaying seizure control in the acute setting. The presence of EPhs at the bedside increases the success of initial phenytoin dosing strategies in this population.
Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline
Authors: Ralston Stuart H , Corral-Gudino Luis , Cooper Cyrus , Francis Roger M , Fraser William D , Gennari Luigi , Guañabens Núria , Javaid M Kassim , Layfield Robert , O'Neill Terence W , Russell R Graham G , Stone Michael D , Simpson Keith , Wilkinson Diana , Wills Ruth , Zillikens M Carola , Tuck Stephen P
Published: February 2019

An evidence-based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Dexamethasone downregulates expression of several genes encoding orphan nuclear receptors that are important to steroidogenesis in stallion testes
Authors: Valdez Raul , Cavinder Clay A. , Varner Dickson D. , Welsh Thomas H. , Vogelsang Martha M. , Ing Nancy H.
Published: February 2019

Glucocorticoids impair testosterone synthesis by an unknown mechanism. Stallions treated with the synthetic glucocorticoid dexamethasone had testes collected at 6 or 12 hours postinjection. The testicular expression of selected genes encoding nuclear receptors and steroidogenic enzymes was measured. At 6 hours, dexamethasone treatment decreased levels of NR0B2,
NR4A1,
NR5A1, and
NR5A2 messenger RNAs (mRNAs) and
NR5A2 mRNA levels remained depressed at 12 hours. In contrast, dexamethasone increased levels of
NFKBIA mRNA at both time points. At 6 hours, dexamethasone did not alter levels of
NR0B1,
NR2F1,
NR2F2,
NR3C1,
CYP11A1,
CYP17A1,
CYP19A1,
DHCR24,
GSTA3,
HSD3B2,
HSD17B3,
LHCGR, or
STAR mRNAs. In primary cultures of Leydig cells, 10
−9 and 10
−7M dexamethasone decreased levels of
NR4A1 and
NR5A1 mRNAs and increased those of
NFKBIA mRNA. Our discovery that dexamethasone downregulates
NR4A1,
NR5A1, and
NR5A2 genes, known to be important for testicular functions, may be part of the mechanism by which glucocorticoids acutely decreases testosterone.
The effect of N‐acetylcysteine supplementation on the oxidative stress levels, apoptosis, DNA damage, and hematopoietic effect in pesticide‐exposed fish blood
Authors: Ucar Arzu , Özgeriş Fatma Betül , Yeltekin Aslı Çilingir , Parlak Veysel , Alak Gonca , Keleş Mevlüt Sait , Atamanalp Muhammed
Published: February 2019

Cysteine is important for protein synthesis, detoxification, and diverse metabolic functions. However, cysteine metabolism has been poorly described in fish, and the role of the therapeutic effect in pesticide toxicology on aquatic organisms is unknown. The aim of this study was to determine the effects of regular cysteine treatment on the hematology, biochemistry, apoptosis, oxidative DNA damage, and antioxidant parameters in fish blood after chemical application. Therefore, fish were exposed to cypermethrin for 2 weeks. Then two different concentrations of N‐acetylcysteine (NAC) were applied for a 4‐day treatment period and compared with the group of the self‐healing process. At the end of the treatment, the hematological index, blood biochemical parameters, paraoxonase (PON), arylesterase (ARE), and myeloperoxidase (MPO) activities in the fish blood samples were investigated. With regard to the hematological parameters, statistical differences were obtained except for mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). Enzyme activities (ARE, PON, and MPO), as well as some biochemical parameters (creatinin [Cre], alanine amino transferase, total glyceride, alkaline phosphatase, iron, calcium, low density lipoprotein‐cholesterol [LDL‐C], sodium, and potassium), were found to be importantly different among all groups at the
P < 0.05 level, while 8‐hydroxydeoxyguanosine and caspase‐3 levels were determined to be high in the pesticide group but decreased significantly in NAC‐treated groups (
P < 0.05). According to the results of the study, acute cysteine treatment showed an ameliorative effect on the hematological index, biochemical parameters, PON, MPO, and ARE in the blood in the all the treatment group fish. The positive effect of NAC on protein synthesis, detoxification, and diverse metabolic functions against cypermethrin toxicity was more effective in 1.0 mM NAC. NAC has an important therapeutic effect on pesticide‐induced hematoxicity for fish in terms of all the data.
The antidiabetic and anticholinergic effects of chrysin on cyclophosphamide‐induced multiple organ toxicity in rats: Pharmacological evaluation of some metabolic enzyme activities
Authors: Taslimi Parham , Kandemir Fatih Mehmet , Demir Yeliz , İleritürk Mustafa , Temel Yusuf , Caglayan Cuneyt , Gulçin İlhami
Published: February 2019

Chrysin (CH) or 5,7‐dihydroxyflavone is a flavonoid present in various plants, bee propolis, and honey. Cyclophosphamide (CYP) is a chemotherapeutic drug, which is extensively used in the treatment of multiple human malignancies. In our study, we aimed to investigate the effects of CYP and CH on some metabolic enzymes including carbonic anhydrase, aldose reductase, paraoxonase‐1, α‐glycosidase, acetylcholinesterase, and butyrylcholinesterase enzyme activities in the brain, heart, testis, liver, and kidney tissues of rats. Thirty‐five adult male Wistar rats were used. The animals were pretreated with CH (25 and 50 mg/kg b.w.) for seven days before administering a single dose of CYP (200 mg/kg b.w.) on the seventh day. In all the tissues, the treatment of CH significantly regulated these enzyme activities in CYP‐induced rats. These results showed that CH exhibited an ameliorative effect against CYP‐induced brain, heart, liver, testis, and kidney toxicity.
RNA‐Seq analysis of differentially expressed genes relevant to mismatch repair in aging hematopoietic stem‐progenitor cells
Authors: Lian Xiaolan , Dong Yongpin , Zhao Mingyi , Liang Yajie , Jiang Weiwei , Li Wenfang , Zhang Lina
Published: February 2019

We used RNA‐sequencing (RNA‐Seq) technology and an old hematopoietic stem and progenitor cells (HSPCs) model in vitro to analyze differential expressions of mismatch repair (MMR)‐related genes in aged HSPCs, so as to explore the mechanism of DNA MMR injury in hematopoietic stem cells (HSC) aging. In this study, by combining RNA‐seq data and National Center for Biotechnology Information database, we focus on six widely reported MMR genes MSH2, MSH3, MSH6, MLH1, PMS1, PMS2, and five MMR genes with closer ties to HSC aging Pcna, Exo1, Rpa1, Rpa2, and Rpa3 according to the genes functional classification and the related signaling pathway. It is concluded that MMR is closely related to HSC aging. This study provides experimental evidence for future researching MMR in HSC aging.
NOS1‐derived nitric oxide facilitates macrophage uptake of low‐density lipoprotein
Authors: Roy Anjali , Banerjee Sreeparna , Saqib Uzma , Baig Mirza S.
Published: February 2019

Foam cell formation is a hallmark event during atherosclerosis. The current paradigm is that lipid uptake by a scavenger receptor in macrophages initiates necrosis core formation that characterizes atherosclerosis. We report that NOS1‐derived nitric oxide (NO) facilitates low‐density lipoprotein (LDL) uptake by macrophages independent of the inflammatory response. LDL uptake could be dramatically suppressed by NOS1 specific inhibitor 1‐(2‐trifluoromethylphenyl) imidazole (TRIM). Importantly, the notion that NOS1 can mediate uptake of lipoproteins suggests that the foam cell formation is regulated by NOS1‐derived NO‐mediated mechanism. This is a novel study involving NOS1 as a critical player of foam cell formation and reveals much about the key molecular proteins involved in atherosclerosis. Targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages and hence dampening the atherosclerosis progression.
Umbilical cord blood mesenchymal stem cells application in hematopoietic stem cells expansion on nanofiber three‐dimensional scaffold
Authors: Darvish Maryam , Payandeh Zahra , Soleimanifar Fatemeh , Taheri Behnaz , Soleimani Masoud , Islami Maryam
Published: February 2019

Umbilical cord blood (UCB) hematopoietic stem cells (HSCs) transplantation (HSCTs) is considered as a therapeutic strategy for malignant and nonmalignant hematologic disorders. Nevertheless, the low number of HSCs obtained from each unit of UCB can be a major challenge for using these cells in adults. In addition, UCB is a rich source of mesenchymal stem cells (MSCs) creating hopes for nonaggressive and painless treatment in tissue engineering compared with bone marrow MSCs. This study was designed to evaluate the effects of UCB‐MSCs application in UCB‐HSCs expansion on the nanoscaffold that mimics the cell's natural niche. To achieve this goal, after flow cytometry confirmation of isolated HSCs from UCB, they were expanded on three‐dimensional (3D) poly‐l‐lactic acid (PLLA) scaffolds fabricated by electrospinning and two‐dimensional (2D)‐culture systems, such as (1) HSCs‐MSCs culturing on the scaffold, (2) HSCs culturing on the scaffold, (3) HSCs‐MSCs culturing on 2D, and (4) HSCs culturing on 2D. After 7 days, real‐time polymerase chain reaction (PCR) was performed to evaluate the CXCR4 gene expression in the mentioned groups. Moreover, for the next validation, the number of total HSCs, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide assay, scanning electron microscopy imaging, and colony‐forming unit assay were evaluated as well. The results of the study indicated that UCB‐MSCs interaction with HSCs in 3D‐culture systems led to the highest expansion of UCB‐HSCs on day 7. Flow cytometry results showed the highest purity of HSCs cocultured with MSCs. Real‐time PCR showed a significant increase in gene expression of CXCR4 in the mentioned group. The highest viability and clonogenicity were detected in the mentioned group too. Considered together, our results suggest that UCB‐HSCs and MSCs coculturing on PLLA scaffold could provide a proper microenvironment that efficiently promotes UCB‐HSCs expansion and UCB‐MSCs can also be considered as a promising candidate for UCB‐HSCTs.
A20 overexpression exerts protective effects on podocyte injury in lupus nephritis by downregulating UCH‐L1
Authors: Sun Ling , Zou Lu‐Xi , Han Yu‐Chen , Wu Ling , Chen Ting , Zhu Dong‐Dong , Hu Po
Published: February 2019

Lupus nephritis (LN), an autoimmune kidney disease caused by systemic lupus erythematosus (SLE), is the inflammation of the kidney. Although the treatment of LN is still a therapeutic challenge for many practitioners, the present study aims to provide a new insight for the treatment and management. The study aims to explore the effect of A20 on LN in relation to the nuclear factor‐kappa B (NF‐κB) signaling pathway. MRL/lpr mice were used as the LN mouse model. Next, A20, UCH‐L1, and NF‐κB expression in LN patients and MRL/lpr mice was determined. A20 was upregulated in podocytes to assess biological functions of A20 in LN. Furthermore, to further investigate the pivotal role of the NF‐κB pathway in LN, the NF‐κB pathway was blocked in podocytes. Next, UCH‐L1 was downregulated in MRL/lpr mice to assess biological functions of UCH‐L1 in LN. A20 was downregulated, whereas UCH‐L1 was upregulated in LN. Overexpressed A20 declined NF‐κB, UCH‐L1 expression, and the extent of p65 phosphorylation. A20 overexpression or UCH‐L1 inhibition increased expression of synaptoporin and nephrin but decreased desmin expression and ubiquitin accumulation level in podocytes. Moreover, A20 overexpression or UCH‐L1 inhibition increased the podocyte number but decreased protein level of cleaved caspase‐3, podocyte lesion improvement, decreased foot process width, glomerulus basement membrane, and foot process fusion rate. In addition, urine protein, blood urea nitrogen, serum creatinine, and ds‐DNA antibody levels decreased with elevated A20 or depleted UCH‐L1. Collectively, it could be concluded that A20 protects against podocyte injury in LN via UCH‐L1 by inactivating the NF‐κB signaling pathway.