bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the relative dose intensity on survival of patients with high‐risk myelodysplastic syndromes treated with Azacitidine
Authors: Laribi Kamel , Bolle Delphine , Alani Mustafa , Ghnaya Habib , Besançon Anne , Farhi Jonathan , Mheidly Kayane , Denizon Nathalie , Baugier de Materre Alix
Published: April 2019

We performed a retrospective analysis of 93 myelodysplastic syndromes (MDS) patients with intermediate 2 or high‐risk IPSS score to study the impact of Azacitidine (AZA) relative dose intensity (RDI) <80% on the overall survival (OS). There were 51.6% of patients who had full dose and 48.4% had dose reduction or delayed with a RDI <80%. Nineteen patients (20.4%) had RDI <80% before getting objective response. Overall and progression‐free survivals (OS, PFS) probabilities for the whole population were 58% (95% CI: 48‐69) and 47% (95% CI: 38‐58) at 1 year; 35% (95% CI: 26‐47) and 31% (95% CI: 23‐43) at two years, respectively. When analyzing the outcomes according to the response to AZA, median OS was 32 months (range: 26‐55) for responders and 8 months (range: 7‐12) for nonresponders, with a respective 1‐year and 2‐year OS probabilities of 91% vs 28% and 66% vs 6%, respectively (P < 0.001). Interestingly, there was no impact of dose reduction on OS nor on PFS, however, when analyzing the timing of dose reduction as time‐dependent variable, we found that patients who had dose reduction before achieving the objective response, had significantly lower OS (P = 0.02) and PFS (P = 0.01) compared to patients who had dose reduction after achieving the objective response. In multivariate analysis, acute myeloid leukemia with 21%‐30% blasts in BM and poor and very poor karyotype significantly impacted OS, (HR = 2.09, 95% CI: 1.27‐3.44, P = 0.004, and HR = 2.73, 95% CI: 1.6‐4.6, P < 0.001 respectively), as well as PFS (HR = 1.84, 95% CI: 1.07‐3.17, P = 0.028, and HR = 3.03, 95% CI: 1.7‐5.39, P < 0.001, respectively).
Expression of immune checkpoint receptors Indoleamine 2,3‐dioxygenase and T cell Ig and ITIM domain in metastatic versus nonmetastatic choroidal melanoma
Authors: Stålhammar Gustav , Seregard Stefan , Grossniklaus Hans E.
Published: April 2019

Background

Survival in metastasized cutaneous melanoma (CM) has been improved with the advent of inhibitors of immune checkpoints CTLA4 and PD‐1. In contrast, the response rate for inhibition of these checkpoints in uveal melanoma (UM) is very low. Other checkpoints including IDO and TIGIT may be targetable.

Methods

Sections from 6 patients with UM, who had undergone primary enucleation 1978—1995 and 6 paired liver metastases were stained immunohistochemically (SOX10, Melan‐A, IDO, TIGIT, and CD8). Four tumors from patients who did not develop metastasis during a mean follow‐up of 19 years, and 5 samples each of normal choroidal and liver tissue were included for comparison. The number of cells/mm2 expressing IDO, TIGIT and CD8 was counted with manual and digital image analysis methods. Retrospective data on patient and tumor characteristics was reviewed.

Results

The number of TIGIT positive cells was significantly higher in primary tumors from patients who eventually developed metastases (mean 4695 cells/mm2) than from patients who didn't (mean 1342 cells/mm2, P < 0.01) and paired metastases (463 cells/mm2, P < 0.01). The number of IDO positive cells was not significantly higher in metastatic tumors (P = 0.079), but the number of IDO and TIGIT positive cells/mm2 correlated in both hot spots (R2 = 0.24, P < 0.01) and full tumor sections (R2 = 0.35, P < 0.01).

Conclusion

The expression of immune checkpoint receptor TIGIT is increased in primary uveal melanomas that seed metastases, and correlates with the expression of checkpoint receptor IDO. Both may be future targets for therapy.
Management of subcutaneous facial emphysema secondary to a class V dental restoration
Authors: Mascarenhas Raoul Julio
Published: April 2019

Key Clinical Message

Subcutaneous facial emphysema (SFE) is a potentially serious complication of dental treatment typically associated with surgical removal of teeth using air‐driven handpieces. A case of SFE is presented occurring after routine dental restoration, along with a framework to aid prevention of this complication and guide management where it occurs.
Smoldering type adult T‐cell leukemia/lymphoma effectively treated with mogamulizumab (anti‐CC chemokine receptor 4 monoclonal antibody)—A case report
Authors: Nishikawa Yotaro , Mochida Kosuke , Kubo Tamaki , Horikawa Nagako , Nemoto Rieko , Amano Masahiro
Published: April 2019

Key Clinical Message

The use of mogamulizumab needs careful consideration because of severe adverse reactions such as graft‐vs‐host disease. However, refractory specific skin lesions of smoldering type adult T‐cell leukemia/lymphoma can be effectively treated with mogamulizumab when patients have no opportunity to receive hematopoietic stem cell transplantation like our case.
Phosphinine‐Based Ligands in Gold‐Catalyzed Reactions
Authors: Rigo Massimo , Habraken Evi R. M. , Bhattacharyya Koyel , Weber Manuela , Ehlers Andreas W. , Mézailles Nicolas , Slootweg J. Chris , Müller Christian
Published: April 2019

A series of substituted phosphinines, 1‐phosphabarrelenes and 5‐phosphasemibullvalenes were synthesized and evaluated for their potential application as ligands in homogeneous catalytic reactions. While their buried volume (%Vbur) was calculated to get insight into the steric properties, [LNi(CO)3] complexes were prepared in order to determine the corresponding Tolman electronic parameter. ETS‐NOCV (extended‐transition‐state natural orbital for chemical valence) calculations on [LAuCl] complexes further allowed an estimation of the σ‐ and π‐contributions to the L−M interaction. AuI coordination compounds of selected examples were prepared and characterized by single crystal X‐ray diffraction. Finally, the three classes of PIII compounds were successfully used in the AuI‐catalyzed cycloisomerization of N‐2‐propyn‐1‐ylbenzamide, showing very good activities and selectivities, which are comparable with the reported data of cationic phosphorus‐based gold catalysts.
Cross‐Coupling Reaction of Alkenyl Sulfoximines and Alkenyl Aminosulfoxonium Salts with Organozincs by Dual Nickel Catalysis and Lewis Acid Promotion
Authors: Erdelmeier Irene , Bülow Gerd , Woo Chang‐Wan , Decker Jürgen , Raabe Gerhard , Gais Hans‐Joachim
Published: April 2019

In this article, the cross‐coupling reaction (CCR) of exocyclic, axially chiral, and acyclic alkenyl (N‐methyl)sulfoximines with alkyl‐ and arylzincs is described. The CCR generally requires dual Ni catalysis and MgBr2 promotion, which is effective in diethyl ether but not in THF. NMR spectroscopy revealed a complexation of alkenyl sulfoximines by MgBr2 in diethyl ether, which suggests an acceleration of the oxidative addition through nucleofugal activation. The CCR of alkenyl sulfoximines generally proceeds in the presence of Ni(dppp)Cl2 as a precatalyst and MgBr2 with alkyl‐ and arylzincs with a high degree of stereoretention at the C and the S atom. CCR of axially chiral alkenyl sulfoximines with Ni(PPh3)2Cl2 as a precatalyst and ZnPh2 does not require salt promotion and is stereoretentive. The reaction with Zn(CH2SiMe3)2, however, demands salt promotion and is not stereoretentive. CCR of axially chiral α‐methylated alkenyl sulfoximines afforded persubstituted axially chiral alkenes with high selectivity. Alkenyl (N‐triflyl)sulfoximines engage in a stereoretentive CCR with Grignard reagents and Ni(PPh3)2Cl2. Ni‐Catalyzed and MgBr2‐promoted CCR of E‐configured acyclic alkenyl sulfoximines and aminosulfoxonium salts with ZnPh2 and Zn(CH2SiMe3)2 is stereoretentive with Ni(dppp)Cl2 and Ni(PPh3)2Cl2. CCRs of acyclic alkenyl sulfoximines and alkenyl aminosulfoxonium salts, carrying a methyl group at the α position, take a different course and give alkenyl sulfinamides under stereoretention at the S and C atom. CCR of acyclic, exocyclic, and axially chiral alkenyl sulfoximines has been successfully applied to the stereoselective synthesis of homoallylic alcohols, exocyclic alkenes, and axially chiral alkenes, respectively.
Noble Metal Corrosion: Halogen Bonded Iodocarbenium Iodides Dissolve Elemental Gold—Direct Access to Gold–Carbene Complexes
Authors: Holthoff Jana M. , Engelage Elric , Kowsari Alexander B. , Huber Stefan M. , Weiss Robert
Published: April 2019

A common method to dissolve elemental gold involves the combination of an oxidant with a Lewis base that coordinates to the gold surface, thus lowering the metal's redox potential. Herein we report the usage of organic iodide salts, which provide both oxidative power and a coordinating ligand, to dissolve gold under formation of organo‐gold complexes. The obtained products were identified as AuIII complexes, all featuring Au−C bonds, as shown by X‐ray single‐crystal analysis, and can be isolated in good yields. Additionally, our method provides direct access to N‐heterocyclic carbene (NHC‐type) complexes and avoids costly organometallic precursors. The investigated complexes show dynamic behavior in acetonitrile and in the case of the NHC(‐type) complexes, the involved species could be identified as a monocarbene [AuI3(carbene)] and biscarbene complex [AuI2(carbene)2]+.
Microstructure‐ and Theory‐Based Modeling and Simulation of Batteries and Fuel Cells
Authors: Latz Arnulf , Danner Timo , Horstmann Birger , Jahnke Thomas
Published: April 2019

The quality of digitalized design and development processes for advanced electrochemical technologies depends crucially on the accuracy of available models and the level of details at which simulations can be performed. In this article, an overview is given over recent advances in developing coupled models of transport and electrochemistry and simulation tools to investigate and modify very detailed processes in batteries and fuel cells, two of the decisive electrochemical technologies for future energy markets.
Microkinetic Modeling of Nickel Oxidation in Solid Oxide Cells: Prediction of Safe Operating Conditions
Authors: Neidhardt Jonathan P. , Bessler Wolfgang G.
Published: April 2019

Oxidation of the nickel electrode is a severe aging mechanism of solid oxide fuel cells (SOFC) and solid oxide electrolyzer cells (SOEC). This work presents a modeling study of safe operating conditions with respect to nickel oxide formation. Microkinetic reaction mechanisms for thermochemical and electrochemical nickel oxidation are integrated into a 2D multiphase model of an anode‐supported solid oxide cell. Local oxidation propensity can be separated into four regimes. Simulations show that the thermochemical pathway generally dominates the electrochemical pathway. As a consequence, as long as fuel utilization is low, cell operation considerably below electrochemical oxidation limit of 0.704 V is possible without the risk of reoxidation.
Beitrag der chemischen Reaktionstechnik zur Energiewende
Authors: Sauer Jörg , Klemm Elias
Published: April 2019

No abstract.
Lime Application Affects Soil Cadmium Availability and Microbial Community Composition in Different Soils
Authors: Shangguan Yu‐xian , Qin Yusheng , Yu Hua , Chen Kun , Wei Yuan , Zeng Xiangzhong , Zhou Zijun , Guo Song , He Siyi
Published: April 2019

The effect of pH increases following lime (Ca(OH)2) addition on soil cadmium (Cd) availability is examined in three soils. The effect of Ca(OH)2 addition (0–7.5 t ha−1) on crop Cd uptake and microbial community composition is evaluated in pot experiments with Chinese cabbage (Brassica chinensis L.) and rice (Oryza sativa L.). The soil pH increases significantly (by 1.21–2.57) after Ca(OH)2 addition, which may be caused by both biological and chemical factors. The soil water‐exchangeable Cd content decreases substantially from 11.7 to 1.4% with Ca(OH)2 application, and the iron and manganese oxide Cd fractions increase from 24.7 to 37.5%. Ca(OH)2 significantly reduces the exchangeable Cd in acidic soil but has limited effects in neutral soil. Ca(OH)2 can inhibit soil Cd activity and plant Cd absorption in acid soil. With increasing Ca(OH)2 addition, the abundance of microorganisms tends to decrease, especially in the acidic soil, whereas it tends to increase in neutral soil. Principal components analysis and redundancy analysis among the soil environmental factors and the soil microbial phospholipid fatty acids show highly variable microbial community composition among soils and treatments. Soil pH has substantial effects on soil fungi, actinomycetes, and other microorganisms, the abundance of which decreases with increasing soil pH. The continuous use of Ca(OH)2 has no significant effects on the abundance and distribution of soil microorganisms.
Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer
Authors: Laali Kenneth K. , Zwarycz Angela T. , Bunge Scott D. , Borosky Gabriela L. , Nukaya Manabu , Kennedy Gregory D.
Published: April 2019

A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring‐deuterated hexamethoxy‐CUR–BF2 and its corresponding CUR compound were also synthesized from a 2,4,6‐trimethoxybenzaldehyde‐3,5‐d2 precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD‐1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR–BF2 adducts exhibited better overall growth inhibition by NCI‐60 assay, while for other CUR–BF2 adducts the non‐deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR–BF2 adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X‐ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported.
Ivermectin Dosing Strategy to Achieve Equivalent Exposure Coverage in Children and Adults
Authors: Brussee Janneke M. , Schulz Jessica D. , Coulibaly Jean T. , Keiser Jennifer , Pfister Marc
Published: April 2019

Ivermectin is a commonly used broad‐spectrum antiparasitic drug, yet doses that produce consistent exposure coverage across age have not been characterized, and no data are available in children weighing < 15 kg. First, a population pharmacokinetic model is developed based on data from 200 children and 11 adults, treated with 100–600 μg/kg ivermectin. Second, model‐based simulations are performed to identify a dosing strategy that achieves equivalent exposure coverage in children and adults. Median (90% confidence interval) clearance of 0.346 (0.12–0.73) L/hour/kg in pre–school‐aged (2–5 years) children is similar to 0.352 (0.17–0.69) L/hour/kg in school‐aged (6–12 years) children but higher than in adults (0.199 (0.10–0.31) L/hour/kg), resulting in significantly lower exposure in children following a 200 μg/kg dose. Simulations indicate that a dose increase to 300 and 250 μg/kg in children aged 2–5 and 6–12 years, respectively, will achieve equivalent ivermectin exposure coverage in children and adults.
Amide Synthesis from Thiocarboxylic Acids and Amines by Spontaneous Reaction and Electrosynthesis
Authors: Tang Li , Matuska Jack H. , Huang Yu‐Han , He Yan‐Hong , Guan Zhi
Published: April 2019

Amide bond formation is one of the most important basic reactions in chemistry. A catalyst‐free approach for constructing amide bonds from thiocarboxylic acids and amines was developed. The mechanistic studies showed that the disulfide was the key intermediate for this amide synthesis. Thiobenzoic acids could be automatically oxidized to disulfides in air, thioaliphatic acids could be electro‐oxidized to disulfides, and the resulting disulfides reacted with amines to give the corresponding amides. By this method, various amides could be easily synthesized in excellent yields without using any catalyst or activator. The successful synthesis of bioactive compounds also highlights the synthetic utility of this strategy in medicinal chemistry.
Dynamic behavioral modeling of nonlinear circuits using a novel recurrent neural network technique
Authors: Naghibi Zohreh , Sadrossadat Sayed Alireza , Safari Saeed
Published: April 2019

In this paper, a new method called local‐global feedback recurrent neural network (LGFRNN) is proposed for dynamic behavioral modeling of nonlinear circuits. The structure of the proposed method is based on recurrent neural network and constructed by time‐delayed local and global feedbacks. Adding time‐delayed feedbacks has a great impact on the learning capability of previous neural network‐based methods. Moreover, time‐delayed local feedbacks alleviate the problem of slow convergency of the conventional neural network‐based methods in the training phase. The proposed LGFRNN can be trained only by having sampled input‐output waveforms of the original circuit without knowing the internal details of the circuit. A training algorithm based on real‐time recurrent learning (RTRL) is used to train LGFRNN. After the training phase, the proposed LGFRNN provides accurate macromodel of a nonlinear circuit. The proposed method is more accurate compared with the conventional neural‐based models (which do not benefit from time‐delayed local‐global feedbacks) and also significantly reduces the training time of the conventional models. Moreover, proposed LGFRNN is faster than the existing models in simulation tools. The validity of the proposed method is verified by time‐domain modeling of three nonlinear devices including commercial TI's SN74AHCT540 device, five‐stage complementary metal‐oxide‐semiconductor (CMOS) receiver, and commercial TI's LM324 power amplifier.
Sitting ducklings: Timing of hatch, nest departure, and predation risk for dabbling duck broods
Authors: Peterson Sarah H. , Ackerman Joshua T. , Herzog Mark P. , Hartman C. Alex , Croston Rebecca , Feldheim Cliff L. , Casazza Michael L.
Published: April 2019

For ground‐nesting waterfowl, the timing of egg hatch and duckling departure from the nest may be influenced by the risk of predation at the nest and en route to wetlands and constrained by the time required for ducklings to imprint on the hen and be physically able to leave the nest. We determined the timing of hatch, nest departure, and predation on dabbling duck broods using small video cameras placed at the nests of mallard (Anas platyrhynchos; n = 26), gadwall (Mareca strepera; n = 24), and cinnamon teal (Anas cyanoptera; n = 5). Mallard eggs began to hatch throughout the day and night, whereas gadwall eggs generally started to hatch during daylight hours (mean 7.5 hr after dawn). Among all species, duckling departure from the nest occurred during daylight (98%), and 53% of hens typically left the nest with their broods 1–4 hr after dawn. For mallard and gadwall, we identified three strategies for the timing of nest departure: (a) 9% of broods left the nest the same day that eggs began to hatch (6–12 hr later), (b) 81% of broods left the nest the day after eggs began to hatch, and (c) 10% of broods waited 2 days to depart the nest after eggs began to hatch, leaving the nest just after the second dawn (27–42 hr later). Overall, eggs were depredated at 10% of nests with cameras in the 2 days prior to hatch and ducklings were depredated at 15% of nests with cameras before leaving the nest. Our results suggest that broods prefer to depart the nest early in the morning, which may best balance developmental constraints with predation risk both at the nest and en route to wetlands.
Differential gene expression in relation to mating system in Peromyscine rodents
Authors: Meléndez‐Rosa Jesyka , Bi Ke , Lacey Eileen A.
Published: April 2019

Behaviors that increase an individual's exposure to pathogens are expected to have important effects on immunoactivity. Because sexual reproduction typically requires close contact among conspecifics, mating systems provide an ideal opportunity to study the immunogenetic correlates of behaviors with high versus low risks of pathogen exposure. Despite logical links between polygynandrous mating behavior, increased pathogen exposure, and greater immunoactivity, these relationships have seldom been examined in nonhuman vertebrates. To explore interactions among these variables in a different lineage of mammals, we used RNAseq to study the gene expression profiles of liver tissue—a highly immunoactive organ—from sympatric populations of the monogamous California mouse (Peromyscus californicus) and two polygynandrous congeners (P. maniculatus and P. boylii). Differential expression and co‐expression analyses revealed distinct patterns of gene activity among species, with much of this variation associated with differences in mating system. This tendency was particularly pronounced for MHC genes, with multiple MHC Class I genes being upregulated in the two polygynandrous species, as expected if exposure to sexually transmitted pathogens varies with mating system. Our results underscore the role of mating behavior in influencing patterns of gene expression and highlight the use of emerging transcriptomic tools in behavioral studies of free‐living animals.
Copper‐Catalyzed Electrophilic Amination of Benzoxazoles via Magnesation
Authors: Lee Sangback , Lee Yunmi
Published: April 2019

One‐pot synthesis of 2‐aminobenzoxazoles through copper‐catalyzed electrophilic amination of benzoxazoles with O‐benzoyl hydroxylamines is described. The direct magnesation of benzoxazoles with the readily available iPrMgCl generated benzoxazolylmagnesium reagents in situ and these reagents were treated with electrophilic amines in the presence of 10 mol‐% Cu(OAc)2 and ZnCl2 under mild reaction conditions. A variety of 2‐aminobenzoxazoles were obtained in good to excellent yields.
Preparation of a capillary isoelectric focusing column with monolithic immobilized pH gradient and its application on protein separation based on an online capillary isoelectric focusing platform
Authors: Liu Rangdong , Pan Hong , Zheng Yiting , Hu Jing , Cheddah Soumia , Wang Weiwei , Wang Yan , Yan Chao
Published: April 2019

In the presence of methanol and n‐decanol as porogens, a partially filled capillary monolithic column was prepared by in situ reaction of glycidyl methacrylate and poly (ethylene glycol) diacrylate. Then, Pharmalyte 3–10 was immobilized on this column in order to obtain a capillary isoelectric focusing (cIEF) column with monolithic immobilized pH gradient (M‐IPG). In addition, an online self‐built platform for protein separation was established on account of the introduction of a cross‐shaped unit and two short‐off valves. In this platform, a cross‐shaped unit was not only used to join the M‐IPG column and a six‐way injection valve (1.5 μL sample loop), but also to supply a volume pool of anode buffer so that the process of injection, focusing and mobilization of samples could be sequentially performed. The short‐off valve in the tee unit or cross‐shaped unit could be used to control the direction of the fluid flow. Using this online cIEF platform and under the optimized conditions, 7‐proteins mixture could be separated and a good linear correlation between pI values and migration times was obtained by the M‐IPG column. Meanwhile, based on the online cIEF platform, human serum proteins and a mixture of Hb A and Hb A1c have been successfully resolved with the newly developed M‐IPG column.
Utilizing SWMM and GIS to identify total suspended solids hotspots to implement green infrastructure in Lucas County, OH
Authors: Bahaya Bernard , Al‐Quraishi Muthana , Gruden Cyndee
Published: April 2019

This research demonstrates that modeling approaches can be used to identify priority areas to implement green stormwater infrastructure (GSI) resulting in improved water quality outcomes. The total suspended solids (TSS) washoff loading from watersheds in Lucas County, Ohio due the municipal separate storm sewer system (MS4) was reported based on 2015 rain data. The highest TSS loading was experienced in the winter season in 80% of the watersheds. Subcatchments with the highest predicted TSS washoff loadings were identified as priority areas or hotspots. In subsequent simulations, GSI implementation in hotspots improved water quality by more than twofold as compared to indiscriminate implementation of GSI. These hotspot maps are being used by regional stormwater stakeholders to focus their urban water quality efforts and to identify site characteristics that may be used to inform environmental policy.
Impacts of successive wildfire on soil hydraulic properties: Implications for debris flow hazards and system resilience
Authors: McGuire Luke A. , Youberg Ann M.
Published: April 2019

Climate and land use changes have led to recent increases in fire size, severity, and/or frequency in many different geographic regions and ecozones. Most post‐wildfire geomorphology studies focus on the impact of a single wildfire but changing wildfire regimes underscore the need to quantify the effects of repeated disturbance by wildfire and the subsequent impacts on system resilience. Here, we examine the impact of two successive wildfires on soil hydraulic properties and debris flow hazards. The 2004 Nuttall‐Gibson Complex and the 2017 Frye Fire affected large portions of the Pinaleño Mountains in southern Arizona, creating a mosaic of burn severity patterns that allowed us to quantify differences in wildfire‐induced hydrologic changes as a function of burn severity and recent fire history (i.e. burned in only the Frye Fire or burned in both fires). Field observations after the 2017 Frye Fire indicated debris flow activity in areas burned predominantly at low severity. Many of these areas, however, were also affected by the 2004 Nuttall‐Gibson Complex, suggesting that the relatively short recovery time between the two wildfires may have played a role in the geomorphic response to the most recent wildfire. Field measurements of soil hydraulic properties suggest that soils burned at moderate severity in 2004 and low severity in 2017 have a lower infiltration capacity relative to those that remained unburned in 2004 and burned at low severity in 2017. Simulations of runoff demonstrate that measured differences in infiltration capacity between once‐ and twice‐burned soils are sufficient in some cases to influence the rainfall intensities needed to initiate runoff generated debris flows. Results quantify the impact of wildfire history and burn severity on runoff and debris flow activity in a landscape affected by successive wildfires and provide insight into how the resilience of geomorphic systems may be affected by successive wildfires. © 2019 John Wiley & Sons, Ltd.
Bioaccumulation and Health Risk Assessment of Heavy Metals in the Soil–Rice System in a Typical Seleniferous Area in Central China
Authors: Chang Chuanyu , Yin Runsheng , Zhang Hua , Yao Linjun
Published: April 2019

Heavy metals are rich in seleniferous areas; however, the bioaccumulation and health risk of heavy metals are poorly understood, given the fact that selenium (Se) can inhibit the phytotoxicity and bioavailability of many heavy metals. The present study investigated the bioaccumulation of heavy metals in the soil–rice system in the Enshi seleniferous area of central China. Soils were contaminated by Mo, Cu, As, Sb, Zn, Cd, Tl, and Hg caused by the weathering of Se-rich shales. Among these heavy metals, Cd and Mo had the highest bioavailability in soils. The bioavailable fractions of Cd and Mo accounted for 41.84 and 10.75% of the total Cd and Mo in soils, respectively. Correspondingly, much higher bioaccumulation factors (BAFs) of Cd (0.34) and Mo (0.46) were found in rice, compared with those of other heavy metals (Zn 0.16, Cu 0.05, Hg 0.04, and Sb 0.0002). For the first time—to our knowledge—we showed that the uptake of Hg, Cd, and Cu by rice could be inhibited by the presence of Se in the soil. The probable daily intake (PDI) of Se, Cd, Mo, Zn, and Cu through consumption of local rice was 252 ± 184, 314 ± 301, and 1774 ± 1326 μg/d; and 7.4 ± 1.68 and 0.87 ± 0.35 mg/d, respectively. The high hazard quotients (HQs) of Mo (1.97 ± 1.47) and Cd (5.22 ± 5.02) suggested a high risk of Cd and Mo for Enshi residents through consumption of rice. Environ Toxicol Chem 2019;38:1577–1584. © 2019 SETAC
Inflammation in mild cognitive impairment due to Parkinson's disease, Lewy body disease, and Alzheimer's disease
Authors: King Eleanor , O'Brien John , Donaghy Paul , Williams‐Gray Caroline H. , Lawson Rachael A. , Morris Christopher M. , Barnett Nicola , Olsen Kirsty , Martin‐Ruiz Carmen , Burn David , Yarnall Alison J. , Taylor John‐Paul , Duncan Gordan , Khoo Tien K. , Thomas Alan
Published: April 2019

Background

Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson disease with the early stages of cognitive impairment (PD‐MCI), patients with prodromal Alzheimer disease (MCI‐AD), prodromal Lewy body disease (MCI‐LB), and controls.

Methods

We obtained venous blood samples from participants with PD‐MCI (n = 44), PD‐normal cognition (n = 112), MCI‐LB (n = 38), MCI‐AD (n = 21), and controls (n = 84). We measured 10 cytokines using Meso Scale Discovery V‐Plex Plus including interferon gamma, interleukin (IL)‐10, IL‐12p70, IL‐13, IL‐1beta, IL‐2, IL‐4, IL‐6, IL‐8, and tumour necrosis factor alpha. High‐sensitivity C‐reactive protein was measured.

Results

There was a higher level of inflammation in patients with MCI‐AD and MCI‐LB compared with controls. PD noncognitively impaired had higher inflammatory markers than controls, but there was no difference between PD‐MCI and controls. There was a decrease in inflammatory markers with increasing motor severity based on the Unified Parkinson's Disease Rating Scale.

Conclusions

Inflammation may be involved in the onset of cognitive decline in patients with MCI‐AD and MCI‐LB but appears to be less prominent PD‐MCI albeit in a small data set. This suggests that anti‐inflammatory medications may have most benefit at the earliest stages of neurodegenerative diseases. For PD cases, this might be in advance of the development of MCI.
A survey on the prevalence of apathy in elderly people referred to specialized memory centers
Authors: Manera Valeria , Fabre Roxane , Stella Florindo , Loureiro Júlia Cunha , Agüera‐Ortiz Luis , López‐Álvarez Jorge , Hanon Cécile , Hoertel Nicolas , Aalten Pauline , Ramakers Inez , Zeghari Radia , Robert Philippe
Published: April 2019

Background

Apathy is a pervasive neuropsychiatric syndrome in people with neurocognitive and psychiatric disorders. The diagnostic criteria for apathy (DCA) have been revised in 2018.

Objectives

Employing the 2018 DCA, in the present study, we investigated in groups of elderly subjects suffering from different neuropsychiatric disorders (a) the apathy prevalence; (b) the most commonly affected apathy dimensions (behavior/cognition, emotion, and social interaction); (c) the sensitivity and specificity of those dimensions for apathy diagnosis; and (d) the concurrent validity of 2018 DCA compared with the 2009 DCA.

Methods

This multicenter survey included 166 subjects. Each center checked the presence of apathy in subjects belonging to the following DSM‐5 diagnoses: mild neurocognitive disorders (mild NCDs); major NCDs; affective disorders (Aff D); and subjective cognitive decline (SCD).

Results

The frequency of apathy varied significantly based on the diagnostic groups (0% of subjects with apathy in the SCD group; 25% in the mild NCD group; 77% in the major NCD group; and 57% in the Aff. D group). All subjects with apathy fulfilled the criteria for the behavior/cognition dimension, 73.1% fulfilled the criteria for the emotion dimension, and 97.4% fulfilled the criteria for the social interaction dimension. Behavior/cognition showed the highest sensitivity, the copresence of emotion and social interaction the highest specificity. The concordance between the 2009 and the 2018 DCA indicated an almost perfect agreement.

Conclusions

These results are consistent with previous reports and confirm that the social interaction dimension added to the 2018 DCA is present in most of subjects with apathy referred to specialized memory centers.
Factors associated with misreporting in performance‐based financing in Burkina Faso: Implications for risk‐based verification
Authors: Kuunibe Naasegnibe , Lohmann Julia , Schleicher Michael , Koulidiati Jean‐Louis , Robyn Paul Jacob , Zigani Zambendé , Sanon Adama , De Allegri Manuela
Published: April 2019

Performance‐based financing (PBF) has been piloted in many low‐ and middle‐income countries (LMICs) as a strategy to improve access to and quality of health services. As a key component of PBF, quantity verification is carried out to ensure that reported data matches the actual number of services provided. However, cost concerns have led to a call for risk‐based verification. Existing evidence suggests misreporting is associated with factors such as complexity of indicators, high service volume, and accepted error margin. In contrast, evidence on the association of key facility characteristics with misreporting in PBF is scarce. We contributed to filling this gap in knowledge by combining administrative data from a large‐scale pilot PBF program in Burkina Faso with data from a health facility assessment in the context of an impact evaluation of the intervention. Our results showed the coexistence of both overreporting and underreporting and that misreporting varied by service indicator and health district. We also found that the number of clinical staff at the facility, the population size in the facility catchment area, and the distance between the facility and the district administration were associated with the probability of misreporting. We recommend further research of these factors in the move towards risk‐based verification. In addition, given that our analysis identified relevant associations, but could not explain them, we recommend further qualitative inquiry into verification processes.
Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone
Authors: Akel Umar , Robinson Marie‐Eve , Werier Joel , Rampersaud Raja , Rakhra Kawan , Johnston Donna , Konji Victor N , Ma Jinhui , Pagé Marika , Matzinger Mary Ann , Ward Leanne M
Published: April 2019

Giant cell tumors of bone (GCTB) may be difficult to resect because of size or location. We describe two adolescents who were treated with denosumab and followed for tumoral and biochemical responses. Denosumab was effective in achieving sufficient regression to allow surgical resection and in preserving peritumor cortical bone. Reactivation of bone resorption markers was noted while the patients were receiving monthly denosumab. One patient suffered a local tumor recurrence. Denosumab was safe in enabling surgical resection of GCTB. However, the effect was transient, with an escape of resorption markers and tumor recurrence. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Combined Collagen-Induced Arthritis and Organic Dust-Induced Airway Inflammation to Model Inflammatory Lung Disease in Rheumatoid Arthritis
Authors: Poole Jill A , Thiele Geoffrey M , Janike Katherine , Nelson Amy J , Duryee Michael J , Rentfro Kathryn , England Bryant R , Romberger Debra J , Carrington Joseph M , Wang Dong , Swanson Benjamin J , Klassen Lynell W , Mikuls Ted R
Published: April 2019

Rheumatoid arthritis (RA) is characterized by extra-articular involvement including lung disease, yet the mechanisms linking the two conditions are poorly understood. The collagen-induced arthritis (CIA) model was combined with the organic dust extract (ODE) airway inflammatory model to assess bone/joint–lung inflammatory outcomes. DBA/1J mice were intranasally treated with saline or ODE daily for 5 weeks. CIA was induced on days 1 and 21. Treatment groups included sham (saline injection/saline inhalation), CIA (CIA/saline), ODE (saline/ODE), and CIA +  ODE (CIA/ODE). Arthritis inflammatory scores, bones, bronchoalveolar lavage fluid, lung tissues, and serum were assessed. In DBA/1J male mice, arthritis was increased in CIA +  ODE >  CIA >  ODE versus sham. Micro-computed tomography (µCT) demonstrated that loss of BMD and volume and deterioration of bone microarchitecture was greatest in CIA +  ODE. However, ODE-induced airway neutrophil influx and inflammatory cytokine/chemokine levels in lavage fluids were increased in ODE >  CIA +  ODE versus sham. Activated lung CD11c+CD11b+ macrophages were increased in ODE >  CIA +  ODE >  CIA pattern, whereas lung hyaluronan, fibronectin, and amphiregulin levels were greatest in CIA +  ODE. Serum autoantibody and inflammatory marker concentrations varied among experimental groups. Compared with male mice, female mice showed less articular and pulmonary disease. The interaction of inhalation-induced airway inflammation and arthritis induction resulted in compartmentalized responses with the greatest degree of arthritis and bone loss in male mice with combined exposures. Data also support suppression of the lung inflammatory response, but increases in extracellular matrix protein deposition/interstitial disease in the setting of arthritis. This coexposure model could be exploited to better understand and treat RA–lung disease. © 2019 American Society for Bone and Mineral Research.
Upregulation of hsa_circ_0136666 contributes to breast cancer progression by sponging miR‐1299 and targeting CDK6
Authors: Liu Li‐Hong , Tian Qing‐Qing , Liu Juan , Zhou Yong , Yong Hongmei
Published: April 2019

Circular RNAs (circRNAs) can participate in multiple cancers, including breast cancer. Increasing circRNAs are recognized in various cancers because of the high‐throughput sequencing. However, the potential physiological effect of hsa_circ_0136666 in breast cancer progression is unknown. In our study, the biological role of hsa_circ_0136666 in breast cancer development was studied. It was displayed that hsa_circ_0136666 was greatly increased in breast cancer. In addition, overexpression of hsa_circ_0136666 was able to promote Michigan Cancer Foundation‐7 (MCF7) and BT474 cell proliferation and triggered cell cycle in G2/M phase. microRNA plays critical role in tumor development and they can act as direct targets of circRNAs. miR‐1299 has been implicated as a famous tumor suppressor in many cancers. Here, miR‐1299 was predicted as the target of hsa_circ_0136666. Meanwhile, its Upregulation repressed breast cancer proliferation, migration and invasion capacity, which could be reversed by the increase of hsa_circ_0136666. Furthermore, Cyclin‐dependent kinase 6 (CDK6) was speculated as the downstream target of miR‐1299. In MCF7 and BT474 cells, CDK6 was greatly overexpressed and it was shown that CDK6 contributed a lot to breast cancer progression. Subsequently, it was implied that hsa_circ_0136666 could modulate CDK6 levels positively in vitro. In conclusion, it was revealed that Upregulation of hsa_circ_0136666 promoted breast cancer progression by sponging miR‐1299 and targeting CDK6.
Silencing of microRNA‐27a facilitates autophagy and apoptosis of melanoma cells through the activation of the SYK‐dependent mTOR signaling pathway
Authors: Tang Hua , Xu Xiaopeng , Xiao Weirong , Liao Yangying , Xiao Xiao , Li Lan , Li Ke , Jia Xiaomin , Feng Hao
Published: April 2019

Melanoma is considered as an aggressive neoplastic transformation and featured with high metastatic potential. Although some studies have provided targets for novel therapeutic interventions, clinical development of targeted drugs for melanoma still remains obscure. Therefore, this study aims to identify the role of microRNA‐27a (miR‐27a) in autophagy and apoptosis of melanoma cells in regulating spleen tyrosine kinase (SYK)‐mediated the mammalian target of rapamycin (mTOR) signaling pathway. A microarray‐based analysis was made to screen differentially expressed genes and predict target miRNA. Melanoma specimens were collected with pigmented nevus as a control. Melanoma cell line Mel‐RM was treated with miR‐27a inhibitor or pcDNA‐SYK to prove their effects on autophagy and apoptosis of melanoma cells. The volume change and tumor mass of nude mice in each group were detected by the tumorigenesis assay. Microarray‐based analysis results showed that SYK was lowly expressed in melanoma cells and may be regulated by miR‐27a. Besides, miR‐27a expression was increased whereas SYK expression was decreased in melanoma tissues. Meanwhile, miR‐27a was positively correlated with tumor stage and lymph node metastasis of melanoma tissues. Furthermore, miR‐27a targeted SYK and silencing of miR‐27a or overexpression of SYK cells promoted autophagy and apoptosis of melanoma cells and reduced their tumorigenic ability in vivo. In conclusion, this study proves that silencing of miR‐27a facilitates autophagy and apoptosis of melanoma cells by upregulating SYK expression and activating the mTOR signaling pathway. The finding offers new ideas for the clinical development of melanoma.
lncRNA TINCR participates in ALA‐PDT‐induced apoptosis and autophagy in cutaneous squamous cell carcinoma
Authors: Zhou Wu , Zhang Shoumin , Li Jianguo , Li Zhenlu , Wang Yuping , Li Xueli
Published: April 2019

This study aims to investigate whether terminal differentiation‐induced ncRNA (TINCR) has an effect on apoptosis and autophagy induced by ALA‐PDT in cutaneous squamous cell carcinoma (CSCC). A431 cells were treated with 5‐aminolevulinic acid (ALA) solution at different concentrations and for different duration time. A431 cell viability was detected by Cell Counting Kit‐8 (CCK‐8) assay, relative TINCR messenger RNA expression was detected by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR). A431 cell apoptosis was examined by flow cytometry. Relative apoptosis/autophagy‐related protein expression was analyzed by Western blot analysis. The effect of TINCR on cell autophagy was detected by RFP‐LC3 immunofluorescence assay. Reactive oxygen species concentration was detected by 2′,7′‐dichlorodihydrofluorescein diacetate (DCFH‐DA) fluorescent probe. Relative expressions of ERK1/2 and specificity protein 3 (Sp3) in A43 cells were detected by Western blot analysis and qRT‐PCR. Sp3 binding sites were analyzed by ChIP‐qPCR. The relative transcription activity was measured with luciferase reporter assay. ALA‐PDT treatment at 3.2 mmol/L for 120 minutes significantly promoted TINCR expression in CSCC A431 cells, and TINCR promoted ALA‐PDT‐induced apoptosis and cell autophagy. Furthermore, ALA‐PDT promoted TINCR expression through ERK1/2‐SP3 pathway. Sp3 promoted TINCR transcription by binding TINCR promoters. Our data indicated that TINCR involves in ALA‐PDT‐induced apoptosis and autophagy in CSCC.
RETRACTED: Identification of Nrf2/STAT3 axis in induction of apoptosis through sub‐G1 cell cycle arrest mechanism in HT‐29 colon cancer cells
Authors: Tajmohammadi Issa , Mohammadian Jamal , Sabzichi Mehdi , Mahmuodi Shiva , Ramezani Mina , Aghajani Marjan , Ramezani Fatemeh
Published: April 2019

We investigated the role of stattic as an adjuvant molecule to increase the cytotoxicity of 5‐fluorouracil (5‐FU) through specific inhibition of molecular targets, signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid 2–related factor 2 (Nrf2) in HT‐29 colon cancer cells. Cytotoxicity and apoptotic effects were investigated by methylthiazolyldiphenyl‐​tetrazolium bromide assay and flow cytometry analysis, respectively. Real‐time polymerase chain reaction was applied to assess the messenger RNA (mRNA) level of STAT3, Nrf2, and apoptotic genes including Bax, Bcl‐xl, and Bcl‐2. The antitumor effect of 5‐FU in combination with stattic induced synergistic effect in HT‐29 cells with combination indexes (CIs) 0.49. Flow cytometric results related to apoptotic confirmed that there was up to 40% increase in the population of apoptotic cells in HT‐29 colon cancer cells incubated with 5‐FU and stattic compared with control groups. Our data from gene expression determined a substantial diminish in the mRNA levels of the Nrf2 and antiapoptotic gene Bcl‐2 along with a noticeable increase in the level of the proapoptotic Bax in HT‐29 colon cells that underwent cotreatment with 5‐FU and stattic (P < 0.05). Moreover, the results exhibited that stattic can be used as adjuvant chemotherapy besides the 5‐FU. This therapeutic approach in colon cancer could mediate 5‐FU chemoresistance via modulating therapeutic targets (ie, STAT3 and Nrf2 pathways) and decreased 5‐FU‐related adverse effects.
Long noncoding RNA HOXA‐AS2 regulates the expression of SCN3A by sponging miR‐106a in breast cancer
Authors: Wu Jie , Li Maolan , Zhang Yijian
Published: April 2019

Breast cancer is the most commonly diagnosed cancer that affects women worldwide. This study aimed to investigate the competing endogenous RNAs (ceRNAs) mechanism in breast cancer. Microarray data were downloaded from the University of California Santa Cruz (UCSC) Xena database. The limma package was used to screen the differentially expressed messenger RNAs (DEMs) and differentially expressed long noncoding RNAs (DELs). Subsequently, functional analysis was performed using DAVID tool. After constructing the protein‐protein interaction (PPI) network, we identified the major gene modules using the Cytoscape software. Univariate survival analysis in the survival package was performed. Finally, the ceRNA regulatory network was constructed to identify the critical genes. A total of 1380 DEMs and 345 DELs were identified in breast cancer samples compared with normal samples. Functional enrichment analysis showed that DEMs were mainly involved in cell division, and cell cycle. We screened four major gene modules and identified the hub nodes in these functional modules. Several DEMs (including FABP7, C4BPA, and LAMB3) and three long noncoding RNAs (lncRNAs) (LINC00092, SLC26A4.AS1, and COLCA1) exhibited significant correlation with patients' survival outcomes. In the ceRNA network, the lncRNA HOXA‐AS2 regulated the expression level of SCN3A by interacting with hsa‐miR‐106a‐5p. Thus, our study investigated the ceRNA mechanism in breast cancer. The results showed that lncRNA HOXA‐AS2 might modulate the expression of SCN3A by sponging miR‐106a in breast cancer.