bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal streamflow extremes are key drivers of Brook Trout young‐of‐the‐year abundance
Authors: Blum Annalise G. , Kanno Yoichiro , Letcher Benjamin H.
Published: August 2018

To manage ecosystems in the context of climate change, we need to understand the relationship between extreme events and population dynamics. Floods and droughts are projected to occur more frequently, but how aquatic species will respond to these extreme events remains uncertain. Based on counts of Brook Trout (Salvelinus fontinalis) collected over 28 yr at 115 sites in Shenandoah National Park, we developed mixed‐effects models to (1) assess how well extreme streamflow, as compared to mean flows and total precipitation, can explain young‐of‐the‐year (YOY) abundance, (2) identify potential nonlinear relationships between seasonal environmental covariates and abundance using nonlinear generalized additive mixed models, and (3) explore likely impacts of expected future weather and streamflow conditions. We found that (1) using covariates of streamflow extremes improved prediction of YOY abundance compared to use of mean seasonal flow values or precipitation as a proxy, (2) warmer maximum daily spring temperatures were associated with increased YOY abundance up to about 1.5 standard deviations, above which abundance declined, and (3) a strong negative effect of extreme winter streamflow, unlikely to be offset by possibly positive effects from other seasons, is expected to have a detrimental impact on Brook Trout populations given predicted increases in winter precipitation. Because YOY abundance is a strong determinant of population dynamics for these short‐lived species, extreme events will have the potential to exert a strong influence on population persistence of Brook Trout in a changing climate. Management actions that maximize resiliency of populations in response to extreme events, such as restoration of habitat connectivity, should be prioritized to buffer negative impacts.
The Quest for Twofold Reductive P–C Bond Cleavage of P–Ph Substituted 1,4‐Dihydro‐1,4‐diphosphinine Derivatives
Authors: Koner Abhishek , Kunz Michael , Schnakenburg Gregor , Streubel Rainer
Published: August 2018

It is demonstrated that backbone chloro(phenyl)phosphanyl‐substituted imidazole‐2‐thiones 3 (N‐R = Me, Et, nBu) can be easily synthesized which allow for a selective access to tricyclic 1,4‐diphenyl‐1,4‐dihydro‐1,4‐diphosphinines 5 via reaction with LDA. Furthermore, new examples for preferred substitution reactions are provided that occurred when KHMDS was used thus yielding P–N(SiMe3)2 substituted derivatives 4. The new P–Ph substituted tricyclic 1,4‐dihydro‐1,4‐diphosphinine derivatives 5 were successfully employed to generate tricyclic bis‐phosphanides 6 using potassium in THF, and the formation of 6 was proven via quenching with excess of n‐butyl iodide to give P–nBu substituted derivatives 7 obtained as mixture of cis and trans isomers.
Selectivity in the Intermolecular Diels–Alder Reaction of Conjugated Trienes: Experimental and Theoretical Approaches
Authors: Remeur Camille , Desrat Sandy , Gandon Vincent , Roussi Fanny
Published: August 2018

Eleven analogs of the natural product meiogynin A, an inhibitor of proteins of the Bcl‐2 family, have been elaborated by an intermolecular Diels–Alder (DA) reaction of various conjugated chloro‐trienes, in order to determine the influence of the modification of the south part of meiogynin A on its biological activity. The chloro‐trienes were obtained in two to five steps from commercial compounds through a selective hydrochlorination of bromoalkyne intermediates to (Z)‐1,2‐dihalogenated alkenes followed by a chemoselective Suzuki–Miyaura cross‐coupling. The intermolecular DA reaction of these trienes with two α,β‐unsaturated carboxylic acids as dienophiles occurred with a perfect regioselectivity and good to excellent diastereoselectivities. These selectivities could be rationalized by DFT calculations.
Why is it so hard to change? The role of self‐integrity threat and affirmation in weight loss
Authors: Logel Christine , Hall William , Page‐Gould Elizabeth , Cohen Geoffrey L.
Published: August 2018

People are frequently dissatisfied with their body weight. Messages alleging that lower weight is esthetically preferable, healthier, and achievable likely trigger chronic self‐integrity threat, the sense that one's personal adequacy is in doubt. We examined whether self‐integrity threat, which creates stress and pressure to restore self‐integrity, contributes to the challenges of weight and behavior change. Weight‐dissatisfied women completed in‐lab tasks including a values affirmation manipulation and two‐month follow‐up. Affirmed women lost weight relative to controls, replicating previous research. Effects were primarily among those with higher initial body masses. Affirmed higher‐weighted women also ate more healthful foods compared to unhealthful foods in self‐reports and observation. Affirmed participants reported increased exercise, and an exploratory measure showed that their cortisol awakening responses synchronized with their coping needs, suggesting more adaptive physiological function. Results suggest that self‐integrity threat is an under‐recognized barrier to change, and reducing it can support healthy changes.
Comparison of NAD with NADP‐dependent Glutamate Dehydrogenase, and CNT with rGO‐modified Electrodes, for the Construction of Glutamate Sensors
Authors: Sato Katsuhiko , Kamijo Toshio , Takahashi Shigehiro , Sato Takaya
Published: August 2018

Glutamate sensors were prepared using nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)‐dependent glutamate dehydrogenase (GDH). Glutamate was determined from the anodic oxidation current of NADH and NADPH generated by the enzymatic reaction of GDH. These two types of GDH enzymes were deposited separately on carbon nanotube (CNT) and reduced graphene oxide (rGO)‐modified glassy carbon electrodes, in which CNT and rGO were used to improve the oxidation capacity of the electrodes. An anodic peak current in response to 1 mM glutamate of glutamate sensors comprising each of these four combinations were compared under the same conditions. The glutamate response was the highest when NAD‐dependent GDH was deposited on the rGO‐modified electrode.
Paternity testing using massively parallel sequencing and the PowerSeq™ AUTO/Y system for short tandem repeat sequencing
Authors: S. B. S. Silva Deborah , Sawitzki Fernanda R. , Scheible Melissa K. R. , Bailey Sarah F. , S. Alho Clarice , Faith Seth A.
Published: August 2018

Massively parallel sequencing (MPS) is gaining attention as a new technology for routine forensic casework, including paternity testing. Recently released MPS multiplex panels provide many more loci compared to CE methods, plus provide sequence‐based alleles that together improve the statistical power of the genetic testing. Here, an MPS system (PowerSeq™ AUTO/Y) was applied for STR sequencing in the study of first‐degree STR sequence allele inheritance from families in Southern Brazil. In 29 trios (mother‐child‐father) analyzed, the paternity index values generally increased when data from sequence‐based analysis were used in comparison to length‐based data. Further, allele inconsistencies (e.g., single repeat mutation events) between child and parents could be resolved with MPS by assessing the core repeat and flanking region sequences. Lastly, the sequence information allowed for identification of isoalleles (alleles of the same size, but different sequence) to determine specific paternal and maternal inheritances. The results from this study showed advantages of implementing sequence‐based analysis, MPS, in paternity testing with improved statistical calculations and a greater resolution for the trios/families tested.
Rapid and efficient western blot assay by rotational cyclic draining and replenishing procedure
Authors: Sajjad Saba , Do Mui Thi , Shin Heung‐Seon , Yoon Tae‐Sung , Kang Sunghyun
Published: August 2018

Western blot is a principal technique for the detection of specific proteins in various biology disciplines. The antibody incubation is an imperative step in western blot. Antibody incubation by mild shaking on a rocker is generally used to facilitate mixing of antibodies. However, mild shaking is an inefficient process to remove antibody depletion layer on blotting membrane and requires hours of incubation time to achieve antibody binding to target proteins. We propose an alternative method of cyclic draining and replenishing (CDR) incubation of antibody solution using a rotational incubation chamber. The study demonstrated that rotational CDR incubation could shorten antibody incubation time with enhanced sensitivity. Moreover, rotational CDR incubation could achieve a stronger antibody binding with lower antibody concentration when compared with batch incubation. In addition, rotational CDR incubation significantly improved the detection of low abundance proteins. This simple modification in western blot procedure makes it rapid, sensitive, and cost‐efficient.
A highly sensitive aptasensor for on‐site detection of lipopolysaccharides in food
Authors: Cheng Cheng , Wu Jayne , Chen Jiangang
Published: August 2018

A rapid, low‐cost, highly sensitive, and specific capacitive aptasensor is presented for detection of lipopolysaccharides (LPS). Exposure to LPS could cause fever, gram‐negative sepsis, septic shock, and eventual death. Hence, rapid, low cost, and sensitive detection of LPS is pivotal for the safety of food, pharmaceutical, and medical devices and products. In this work, a capacitive sensing method based on alternating current electrokinetics is developed to achieve rapid and specific detection of LPS. This method uses an alternating current signal for two purposes. One is to induce positive dielectrophoresis, which attracts LPS toward the sensor electrodes’ surface and accelerates its binding with the immobilized aptamer probe. The other purpose is to simultaneously sense the binding reaction by measuring the interfacial capacitance change on the electrodes’ surface. The testing procedures and instrumentation setup of this sensing platform are significantly simplified while finding quantitative concentrations of both analytical and complex samples within 30 s. When testing analytical samples of LPS from Escherichia coli O55:B5, a LOD of 4.93 fg/mL is achieved. The recovery analysis is also performed with LPS spiked in a complex matrix and good recovery rates are demonstrated. This work provides an affordable and field‐deployable platform for highly sensitive and real‐time LPS detection.
Analysis of Two‐Step Solar Thermochemical Looping Reforming of Fe3O4 Redox Cycles for Synthesis Gas Production
Authors: Guene Lougou Bachirou , Shuai Yong , Chaffa Gédéon , Ahouannou Clément , Pan Ruming , Zhang Hao , Tan Heping
Published: August 2018

A two‐step solar thermochemical looping reforming (STCLR) of CH4—Fe3O4 redox cycles via H2O and CO2 splitting is investigated for H2 and CO production. The P1 approximation is adopted for the radiation heat transfer and high‐temperature thermal characteristics of active materials in the reaction medium. A benchmark experimental setup for the conversion of solar energy to syngas based on the solar thermochemical technology is presented. The effects of operating conditions on the yield of H2 and CO as well as syngas production are investigated at both thermal reduction and oxidation steps. It is found that the key performance of two‐step CH4—Fe3O4 redox cycles for a higher H2 and CO production depends on the efficiency of methane and oxidizer (H2O and CO2) conversion. Furthermore, a substantial amount of H2 and CO production with carbon deposition is obtained when the thermal reduction is extended to the mixed oxide solid solution (FeO—Fe). Among the oxygen carriers, FeO exhibits a higher oxygen exchange for H2 production. However, the synergetic effect of FeO—Fe reactivity strongly contributes to syngas yield. The present solar reactor model can significantly contribute to the reduction of greenhouse gas emission by utilizing 40% of CO2 emissions into solar fuels such as H2 and syngas. The results indicate that highly selective syngas with an H2/CO ratio close to 2 can be obtained with a strong control of γ = H2O/CO2.
The influence of interface geometry, stiffness, and crushing on the dynamic response of masonry collapse mechanisms
Authors: Mehrotra Anjali , DeJong Matthew J.
Published: August 2018

Failure of masonry structures generally occurs via specific collapse mechanisms which have been well documented. Using rocking dynamics, equations of motion have been derived for a number of different failure mechanisms ranging from the simple overturning of a single block to more complicated mechanisms. However, most of the equations of motion derived thus far assume that the structures can be modelled as rigid bodies rocking on rigid interfaces with an infinite compressive strength—which is not always the case. In fact, crushing of masonry—commonly observed in larger scale constructions and vertically restrained walls—can lead to a reduction in the dynamic capacity of these structures. This paper rederives the rocking equation of motion to account for the influence of flexible interfaces, characterized by a specific interface stiffness as well as finite compressive strength. The interface now includes a continually shifting rotation point, the location of which depends not only on the material properties of the interface but also on its geometry. Expressions have thus also been derived for interfaces of different geometries, and parametric studies conducted to gauge their influence on dynamic response. The new interface formulations are also implemented within a new analytical modelling tool that provides a novel approach to the dynamic analysis of masonry collapse mechanisms. Finally, this tool is exemplified, along with the importance of the interface formulation, by evaluating the collapse of the Dharahara Tower in Kathmandu, which was almost completely destroyed during the 2015 Gorkha earthquake.
The persistence of beaver‐induced geomorphic heterogeneity and organic carbon stock in river corridors
Authors: Laurel DeAnna , Wohl Ellen
Published: August 2018

Beavers are widely recognized as ecosystem engineers for their ability to shape river corridors by building dams, digging small canals, and altering riparian vegetation. Through these activities, beavers create beaver meadows, which are segments of river corridor characterized by high geomorphic heterogeneity, attenuation of downstream fluxes, and biodiversity. We examine seven beaver meadows on the eastern side of the Rocky Mountain National Park, Colorado, USA with differing levels of beaver activity. We divide these sites into the four categories of active, partially active, recently abandoned (< 20 years), and long abandoned (> 30 years). We characterize geomorphic units within the river corridor and calculate metrics of surface geomorphic heterogeneity relative to category of beaver activity. We also use measures of subsurface geomorphic heterogeneity (soil moisture, soil depth, percent clay content, organic carbon concentration) to compare heterogeneity across beaver meadow categories. Finally, we calculate organic carbon stock within the upper 1.5 m of each meadow and compare these values to category of beaver activity. We find that surface geomorphic heterogeneity and mean soil moisture differ significantly only between active and long abandoned meadows, suggesting a non‐linear decrease with time following beaver abandonment of a meadow. Soil depth and organic carbon stock do not differ consistently in relation to category of beaver meadow, suggesting that larger‐scale geologic controls that foster deep floodplain soils can continue to maintain substantial organic carbon stocks after beavers abandon a meadow. These results also indicate that the effects of beaver ecosystem engineering can persist for nearly three decades after the animals largely abandon a river corridor. © 2018 John Wiley & Sons, Ltd.
Debris‐flow release processes investigated through the analysis of multi‐temporal LiDAR datasets in north‐western Iceland
Authors: Morino Costanza , Conway Susan J. , Balme Matthew R. , Hillier John , Jordan Colm , Sæmundsson Þorsteinn , Argles Tom
Published: August 2018

Debris flows are fast‐moving gravity flows of poorly sorted rock and soil, mixed and saturated with water. Debris‐flow initiation has been studied using empirical and experimental modelling, but the geomorphic changes, indicative of different triggering processes, are difficult to constrain with field observations only. We identify signatures to distinguish two different debris‐flow release styles by integrating high‐resolution multi‐temporal remote sensing datasets and morphometric analysis. We analyse debris flows sourced above the town of Ísafjörður (Iceland). Two debris‐flow triggering processes were previously hypothesised for this site: (i) slope failure, characterised by landslides evolving into debris flows; and (ii) the fire‐hose effect, in which debris accumulated in pre‐existing, steep‐sided bedrock passages is transported by a surge of water. It is unknown which process dominates and determines the local risk. To investigate this question, we compare airborne LiDAR elevation models and aerial photographs collected in 2007 with similar data from 2013. We find that two new debris‐flow tracks were created by slope failures. These are characterised by steep sliding surfaces and lateral leveed channels. Slope failure also occurred in two large, recently active tracks, creating the preparatory conditions for the fire‐hose effect to mobilise existing debris. These tracks show alternating zones of fill and scour along their length, and debris stored below the source‐area at rest angles >35°. Our approach allows us to identify and quantify the morphological changes produced by slope failure release process, which generated the preparatory conditions for the fire‐hose effect. As debris flows are rarely observed in action and morphological changes induced by them are difficult to detect and monitor, the same approach could be applied to other landscapes to understand debris‐flow initiation in the absence of other monitoring information, and can improve the identification of zones at risk in inhabited areas near hillslopes with potential for debris flows. © 2018 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd.
Look in the trees: Hylobatids as evolutionary models for extinct hominins
Authors: Zichello Julia M.
Published: August 2018

Studying extant apes is of central importance to paleoanthropology. This approach is informative in inferring how hominin skeletal morphology reflects phylogeny, behavior, development, and ecological context. Traditionally, great apes have dominated the paleoanthropological literature as extant analogs for extinct hominins, to the exclusion of their phylogenetic sister group, the hylobatids. Phylogenetic proximity, large body size, and high encephalization quotients may have contributed to decisions to use great apes as models for hominins. However, if we reexamine hylobatids as extant models for extinct hominins—using modern phylogenetic, behavioral, and ecological data—this clade is uniquely poised to inform future frameworks in paleoanthropology. The following features make hylobatids strong analogs for extinct hominins: taxonomic diversity, the timing of diversification, hybridization between species, small body size, and reduced sexual dimorphism. Based on these shared features, hylobatids offer future opportunities to paleoanthropology, and provide a much richer extant analog than is currently recognized.
Adaptive learning from model space
Authors: Prüser Jan
Published: August 2018

Dynamic model averaging (DMA) is used extensively for the purpose of economic forecasting. This study extends the framework of DMA by introducing adaptive learning from model space. In the conventional DMA framework all models are estimated independently and hence the information of the other models is left unexploited. In order to exploit the information in the estimation of the individual time‐varying parameter models, this paper proposes not only to average over the forecasts but, in addition, also to dynamically average over the time‐varying parameters. This is done by approximating the mixture of individual posteriors with a single posterior, which is then used in the upcoming period as the prior for each of the individual models. The relevance of this extension is illustrated in three empirical examples involving forecasting US inflation, US consumption expenditures, and forecasting of five major US exchange rate returns. In all applications adaptive learning from model space delivers improvements in out‐of‐sample forecasting performance.
An analysis on the predictability of CAPM beta for momentum returns
Authors: Cenesizoglu Tolga , Papageorgiou Nicolas , Reeves Jonathan J. , Wu Haifeng
Published: August 2018

This paper demonstrates that the forecasted capital asset pricing model (CAPM) beta of momentum portfolios explains a large portion of the return, ranging from 40% to 60% for stock‐level momentum, and from 30% to 50% for industry‐level momentum. Beta forecasts are from a realized beta estimator using daily returns over the prior year. Periods such as 1969–1989 have been found in earlier studies to contain abnormal profits from momentum trading; however, we show that these were spuriously generated by measurement error in systematic risk. These results cast further doubt on the ability of standard momentum trading strategies to generate abnormal profits.
Cenozoic stage of development of local structures of the Lower Kura Depression and Baku Archipelago related to their oil and gas prospectivity
Authors: Narimanov Nariman , Babayev Nariman , Gahramanov Gahraman , Javad‐Zadeh Zohrab
Published: August 2018

The South Caspian Basin (SCB), including the Lower Kura Depression (LKD), was one of the deep‐sea basins of Tethys before the Late Palaeogene. During the Late Palaeogene, due to the convergence of the Iranian‐Afghan and Anatolian plates with the Eurasian Plate, the SCB was transformed into a marginal sea. By the end of the Miocene, the Arabian Plate converged between Anatolian and Irano‐Afghan, which contributed to fold deformations of north‐eastern orientation in the north‐western part of the Iranian‐Afghan Plate. It led to the development of the western side of SCB and drainage of Kura Depression; since then, the LKD became a western onshore continuation of SCB. A compressive stress regime, established there since the end of the Miocene, directly influenced the structures development process in LKD and Baku Archipelago (BA). Although LKD is located onshore and its eastern edge belongs to SCB west board, together with BA they form a single structural and tectonic zone, which is evidenced by the evolution, spatial orientation of local structures and anticlinal zones. To establish the correlation of the evolution features of LKD and BA, we performed the palaeoanalysis on the basis of reconstructed palaeoprofiles for several LKD and BA structures. From palaeoprofiles, we constructed diagrams of fold growth intensity. The results of the correlation of these diagrams indicate at the consedimentational and continuous character of the development of structures in both zones (except for the buried structures) but featuring different intensity at different intervals of geological time. During the formation time of the Lower Production Series (LPS), both zones were characterized by a relatively rapid growth of the folds. At the time of formation of the Upper Production Series (UPS), Absheron‐Aghjagil structures growth intensity was roughly the same but lower than that of LPS. The most intense growth of folds in both zones occurred in Quaternary time.
The system‐neurophysiological basis for how methylphenidate modulates perceptual–attentional conflicts during auditory processing
Authors: Adelhöfer Nico , Gohil Krutika , Passow Susanne , Teufert Benjamin , Roessner Veit , Li Shu‐Chen , Beste Christian
Published: August 2018

The ability to selectively perceive and flexibly attend to relevant sensory signals in the environment is essential for action control. Whereas neuromodulation of sensory or attentional processing is often investigated, neuromodulation of interactive effects between perception and attention, that is, high attentional control demand when the relevant sensory information is perceptually less salient than the irrelevant one, is not well understood. To fill this gap, this pharmacological‐electroencephalogram (EEG) study applied an intensity‐modulated, focused‐attention dichotic listening paradigm together with temporal EEG signal decomposition and source localization analyses. We used a double‐blind MPH/placebo crossover design to delineate the effects of methylphenidate (MPH)—a dopamine/norepinephrine transporter blocker—on the resolution of perceptual–attentional conflicts, when perceptual saliency and attentional focus favor opposing ears, in healthy young adults. We show that MPH increased behavioral performance specifically in the condition with the most pronounced conflict between perceptual saliency and attentional focus. On the neurophysiological level, MPH effects in line with the behavioral data were observed after accounting for intraindividual variability in the signal. More specifically, MPH did not show an effect on stimulus‐related processes but modulated the onset latency of processes between stimulus evaluation and responding. These modulations were further shown to be associated with activation differences in the temporoparietal junction (BA40) and the superior parietal cortex (BA7) and may reflect neuronal gain modulation principles. The findings provide mechanistic insights into the role of modulated dopamine/norepinephrine transmitter systems for the interactions between perception and attention.
Contributions from cognitive engineering to requirements specifications for complex sociotechnical systems: A case study in the context of healthcare in Brazil
Authors: Jatoba Alessandro , da Cunha Amauri M. , Vidal Mario C. R. , Burns Catherine M. , de Carvalho Paulo V. R.
Published: August 2018

This paper aims at presenting a case study on the use of human factors and ergonomics to enhance requirement specifications for complex sociotechnical system support tools through enhancing the understanding of human performance within the business domain and the indication of high‐value requirements candidates to information technology support. This work uses methods based on cognitive engineering to build representations of the business domain, highlighting workers’ needs, and contributing to the improvement of software requirements specifications, used in the healthcare domain. As the human factors discipline fits between human sciences and technology design, we believe that its concepts can be combined with software engineering to improve understanding of how people work, enabling the design of better information technology.
Potential loss of prognostic significance of minimal residual disease assessment after R‐CHOP‐based induction in elderly patients with mantle cell lymphoma in the era of rituximab maintenance
Authors: Klener Pavel , Fronkova Eva , Kalinova Marketa , Belada David , Forsterova Kristina , Pytlik Robert , Blahovcova Petra , Simkovic Martin , Salek David , Mocikova Heidi , Prochazka Vit , Janikova Andrea , Vaskova Martina , Mejstrikova Ester , Kodet Roman , Trka Jan , Trneny Marek
Published: August 2018

Rituximab maintenance (RM) prolongs survival of elderly patients with mantle cell lymphoma (MCL). Persistent minimal residual disease (MRD) after induction repeatedly correlated with shorter progression‐free survival (PFS). However, none of the published studies analyzed patients treated with RM. The main purpose was to analyze prognostic significance of MRD in the elderly patients with newly diagnosed MCL treated according to the recently published observational trial protocol (alternation of R‐CHOP and R‐cytarabine, 3 + 3 cycles, GovTrial number NCT03054883) at the centers that implemented RM. Minimal residual disease was evaluated by a EuroMRD standardized real‐time PCR approach after 3 and 6 cycles of the induction therapy. Prognostic significance of MRD was analyzed in a subcohort of patients treated at the centers that implemented RM as a standard approach. Bone marrow proved to be a significantly more sensitive source for MRD detection than peripheral blood. In either compartment MRD (positive versus negative) after 3 or 6 cycles of the induction therapy did not correlate with PFS. The observed loss of prognostic significance of MRD after the R‐CHOP‐based induction appears to be a consequence of RM immune control over the residual lymphoma.
The outcome of patients with high‐risk MDS achieving stable disease after treatment with 5‐azacytidine: A retrospective analysis of the Hellenic (Greek) MDS Study Group
Authors: Papageorgiou Sotirios G. , Kontos Christos K. , Kotsianidis Ioannis , Vasilatou Diamantina , Symeonidis Argyris , Galanopoulos Athanasios , Bouchla Anthi , Hatzimichael Eleftheria , Repousis Panagiotis , Zikos Panagiotis , Viniou Nora‐Athina , Poulakidas Elias , Vassilakopoulos Theodoros P. , Diamantopoulos Panagiotis , Diamantopoulos Marios A. , Mparmparousi Despoina , Bouronikou Eleni , Papadaki Helen , Panayiotidis Panayiotis , Pappa Vasiliki
Published: August 2018

The demethylating factor 5‐azacytidine (5‐AZA) improves survival in intermediate‐2 and high‐risk myelodysplastic syndrome (MDS) patients [according to the International Prognostic Score System (IPSS)] responding to treatment. However, the outcome of patients achieving stable disease (SD) is unclear. This retrospective study of the Hellenic MDS Study Group included 353 intermediate‐2 or high IPSS risk patients treated with 5‐AZA. Forty‐four out of 86 (51.6%) patients achieving SD and continuing treatment with 5‐AZA showed a lower risk of transformation of MDS to acute myeloid leukemia (AML) and increased overall survival (OS), compared to SD patients who discontinued the treatment (estimated median AML‐free survival = 38 months, 95% CI = 10.7‐65.3 vs 15 months, 95% CI = 10.4‐19.6, P < .001; estimated median OS = 20 months, 95% CI = 5.5‐34.5 vs 11 months, 95% CI = 5.8‐16.2, P < .001). Moreover, SD patients continuing treatment with 5‐AZA had no differences in AML‐free survival compared to patients showing response to 5‐AZA (estimated median AML‐free survival = 38 months, 95% CI = 10.7‐65.3 vs 31 months, 95% CI = 23.6‐38.4, P = .45; estimated median OS 20 months, 95% CI = 5.5‐34.5 vs 25 months, 95% CI = 21.3‐28.7, P = .50). In conclusion, MDS patients achieving SD in the first 6 months of treatment with 5‐AZA as best response should continue receiving 5‐AZA as they may benefit from prolonged treatment.
Frontline treatment for transplant‐eligible multiple myeloma: A 6474 patients network meta‐analysis
Authors: Sekine Leo , Ziegelmann Patrícia Klarmann , Manica Denise , da Fonte Pithan Carolina , Sosnoski Monalisa , Morais Vinicius Daudt , Falcetta Frederico Soares , Ribeiro Mariana Rangel , Salazar Ana Paula , Ribeiro Rodrigo Antonini
Published: August 2018

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post‐transplant results. Therefore, best frontline treatment for transplant‐eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta‐analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide‐lenalidomide‐dexamethasone) over TD‐based (thalidomide‐dexamethasone, HR = 0.76,0.62‐0.90), VAD‐based (HR = 0.71,0.52‐0.90), and Z‐Dex (idarubicin‐dexamethasone, HR = 0.37,0.17‐0.76) regimens. Concerning PFS, VTD (bortezomib‐thalidomide‐dexametasone) showed superior results when compared with TD‐based (HR = 0.66,0.51‐0.84), VAD‐based (HR = 0.61,0.46‐0.82), Z‐Dex (HR = 0.42,0.22‐0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41‐0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide‐only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide‐doxorubicin‐dexamethasone), neurological with PAD (bortezomib‐doxorubicin‐dexamethasone), infectious with Dex, hematological with Z‐Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant‐eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression‐free survival, when compared with bortezomib/thalidomide protocols.
Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure who reach complete response after rescue treatment
Authors: Jiménez‐Ubieto Ana , Grande Carlos , Caballero Dolores , Yáñez Lucrecia , Novelli Silvana , Hernández‐Garcia Miguel Teodoro , Manzanares María , Arranz Reyes , Ferreiro José Javier , Bobillo Sabela , Mercadal Santiago , Galeo Andrea , Jiménez Javier López , Moraleda José María , Vallejo Carlos , Albo Carmen , Pérez Elena , Marrero Carmen , Magnano Laura , Palomera Luis , Jarque Isidro , Martínez‐Sánchez Pilar , Martín Alejandro , Coria Erika , López‐Guillermo Armando , Salar Antonio , Lahuerta Juan José ,   on behalf of the GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) Cooperative Study Group
Published: August 2018

Patients with follicular lymphoma (FL) who experience early therapy failure (ETF) within 2 years of frontline immunochemotherapy have poor overall survival (OS). We analyzed the Grupo Español de Linfomas y Trasplantes de Médula Ósea registry to determine whether autologous stem cell transplantation (ASCT) is effective in this high‐risk subgroup. Patients with non‐transformed FL treated with rituximab were included in the analysis. ETF was defined as relapse/progression within 2 years of starting first‐line therapy. We identified two groups: the ETF cohort (n = 52; 38 transplanted in second complete response [CR2] and 14 transplanted in second partial response [PR2]), and the non‐ETF cohort (patients receiving ASCT in either CR2 [n = 14] or PR2 [n = 2], but who did not experience ETF following first‐line therapy). There were no differences in 5‐year progression‐free survival (PFS) (49% vs 60%, respectively, P = 0.49) nor in 5‐year OS (81% vs 83%, respectively, P = 0.8) between the ETF and non‐ETF cohorts. Moreover, in the subgroup of patients who presented an interval from first relapse after primary treatment to ASCT of <1 year, there were neither differences in terms of PFS (49% vs 66%, respectively, P = 0.44) nor in OS (86% vs 85%, respectively, P = 0.9) between both cohorts. Patients in the ETF cohort transplanted in CR showed a plateau in the PFS curves beyond 7 years of follow‐up, at 50%. Patients presenting ETF after frontline therapy lack standard therapeutic options. ASCT may be a curative option for ETF in patients who respond to rescue treatments and should be considered an early consolidation option.
Impact of the doctor deficit on hospital management in Poland: A mixed‐method study
Authors: Dubas‐Jakóbczyk Katarzyna , Domagała Alicja , Mikos Marcin
Published: August 2018

Objectives

The primary objective was to assess the scale and consequences of the doctor deficit in Poland with the main focus on hospital care providers. To provide the background for the above, an analysis of the system level responses to the problem was also conducted.

Data and methods

A mixed‐method approach was used. We triangulated data collected using 3 methods: (1) a literature review, (2) an analysis of the national statistical databases, and (3) in‐depth interviews with hospital managers.

Results

Poland is characterized by the lowest number of physicians per 1000 population in the European Union (2.3 in 2015). Also, the age structure of the doctor working population constitutes an alarming factor (in 2015, approx. 48% of all practicing doctors and 61% of specialists were above 50). In recent years, numerous hospitals were forced to cease provision of specific services and/or close wards due to the doctor deficit. The high competition in employing doctors and pressure for wage increases puts hospital managers in situations where they must often choose between securing service provision (by offering higher wages for doctors) and maintaining the hospital's positive financial outcome (by containing costs).

Conclusion

In Poland, the long‐term neglect of health workforce planning at the system level (there is neither a dedicated structure nor a formal strategy) has contributed to the current doctor deficit crisis. From the hospital managers' perspective, who are on the frontline of the problem impact, urgent solutions are needed that would at least alleviate its scale in the short term.
Barriers and facilitators to implementation of essential health benefits package within primary health care settings in low‐income and middle‐income countries: A systematic review
Authors: El‐Jardali Fadi , Fadlallah Racha , Daouk Aref , Rizk Rana , Hemadi Nour , El Kebbi Ola , Farha Aida , Akl Elie A.
Published: August 2018

Background

One of the key requirements for achieving universal health coverage is the proper design and implementation of essential health benefits package (EHPs). We systematically reviewed the evidence on barriers and facilitators to the implementation of EHPs within primary health care settings in low‐income and middle‐income countries.

Methods

We searched multiple databases and the gray literature. Two reviewers completed independently and in duplicate data selection, data extraction, and quality assessment. We synthesized the findings according to the following health systems arrangement levels: governance, financial, and delivery arrangements.

Results

Ten studies met the eligibility criteria. At the governance level, key reported barriers were insufficient policymaker‐implementer interactions, limited involvement of consumers and stakeholders, sub‐optimal primary health care network arrangement, poor marketing and promotion of package, and insufficient coordination with community network. The key reported facilitator was the presence of a legal policy framework for package implementation. At the financial level, barriers included delays and inadequate remunerations to health care providers while facilitators included government and donor commitments to financing of package and flexibility in exploring new funding mechanisms. At the delivery level, barriers included inadequate supervision, poor facility infrastructure, limited availability of equipment and supplies, and shortages of workers. Facilitators included proper training and management of workforce, availability of female health workers, presence of clearly defined packages, and continuum of care, including referrals to promote comprehensive service delivery.

Conclusion

We identified a set of barriers and facilitators that need to be addressed to ensure proper implementation of EHPs within primary health care settings.
Prospective study of sentinel lymph node mapping for endometrial cancer
Authors: Togami Shinichi , Kawamura Toshihiko , Fukuda Mika , Yanazume Shintaro , Kamio Masaki , Kobayashi Hiroaki
Published: August 2018

Objective

To evaluate sentinel lymph node (SLN) mapping for endometrial cancer, using radioisotope and indocyanine green (ICG) injections.

Methods

A prospective study was conducted between April 1, 2014, and December 27, 2017, among women with endometrial cancer, excluding those with suspected peritoneal dissemination and lymph node metastasis, at a University hospital in Kagoshima, Japan. Patients with low‐risk endometrial cancer underwent pelvic SLN mapping using uterine cervix radioisotope injections; intermediate/high‐risk patients underwent pelvic SLN with/without intraoperative para‐aortic SLN mapping with ICG subserosal injections. Primary endpoints were estimated detection rates, sensitivity, and negative predict values (NPV) of SLN mapping.

Results

Of 113 patients evaluated, comprehensive pelvic lymphadenectomy was performed after SLN detection in all patients; additional para‐aortic lymphadenectomy was performed in 38 (34%) patients. The detection rates for pelvic SLN (≥1), bilateral pelvic SLN, and para‐aortic SLN (≥1) were 96%, 80%, and 55%, respectively. Pelvic and para‐aortic lymph node metastasis were found in (10%) (12/113) and 18% (6/33) patients, respectively. Isolated para‐aortic lymph node metastasis was not observed. In pelvic SLN analysis, sensitivity was 91% and NPV was 99%. In para‐aortic SLN analysis, sensitivity and NPV were 100%.

Conclusion

SLN biopsy may be useful to avoid comprehensive pelvic lymphadenectomy in low‐risk patients. In high‐risk patients, SLN mapping revealed high detection rates, sensitivity, and NPV, including those for para‐aortic SLN.
Micro‐RNAs as critical regulators of matrix metalloproteinases in cancer
Authors: Noruzi Somaye , Azizian Mitra , Mohammadi Rezvan , Hosseini Seyede Atefe , Rashidi Bahman , Mohamadi Yousef , Nesaei Abolfazl , Seiri Parvaneh , Sahebkar Amirhossein , Salarinia Reza , Aghdam Arad Mobasher , Mirzaei Hamed
Published: August 2018

Metastasis is known to be one of the important factors associated with cancer‐related deaths worldwide. Several cellular and molecular targets are involved in the metastasis process. Among these targets, matrix metalloproteinases (MMPs) play central roles in promoting cancer metastasis. MMPs could contribute toward tumor growth, angiogenesis, migration, and invasion via degradation of the extracellular matrix and activation of pre‐pro–growth factors. Therefore, identification of various cellular and molecular pathways that affect MMPs could contribute toward a better understanding of the metastatic pathways involved in various tumors. Micro‐RNAs are important targets that could affect MMPs. Multiple lines of evidence have indicated that deregulation of various micro‐RNAs, including miR‐9, Let‐7, miR‐10b, and miR‐15b, affects metastasis of tumor cells via targeting MMPs.
Circ_0056618 and CXCR4 act as competing endogenous in gastric cancer by regulating miR‐206
Authors: Li Hongbo , Yao Guoliang , Feng Bing , Lu Xueliang , Fan Yonggang
Published: August 2018

Circular RNAs (circRNAs) have proved to play an important role in gastric cancer. In this study, we found that circ_0056618 took part in gastric cancer cell proliferation and survival. The real‐time polymerase chain reaction result showed that circ_0056618 was overexpressed in tumor tissues or cells compared with adjacent normal tissues or normal cells and had a negative relationship to gastric cancer patients’ survival time. Meanwhile, the inhibition of circ_0056618 suppressed the proliferation and metastasis of gastric cancer cells. Further bioinformatical analysis indicated that circ_0056618 sponged miR‐206 to regulate CXCR4 according to the prediction of TargetScan and miRanda. Dual‐luciferase reporter assay and Western blot analysis revealed the underlying relationship of circ_0056618, miR‐206, and CXCR4. Hence, circ_0056618 negatively regulated miR‐206 expression promoting CXCR4 expression. Altogether, circ_0056618 is a potential gastric cancer prognostic marker, as well as a potential therapeutic target to inhibit gastric cancer metastasis.
Long noncoding RNA TUG1 promotes cell proliferation and migration of renal cell carcinoma via regulation of YAP
Authors: Liu Shan , Yang Yantong , Wang Weiwei , Pan Xiaoyue
Published: August 2018

Objectives: Recently, long noncoding RNAs (lncRNAs) have captured much attention for their important roles in human diseases. Deregulation of lncRNA taurine‐upregulated gene 1 (TUG1) has been reported to regulate cancer progression in many cancer types. However, how TUG1 contributes to renal cell carcinoma (RCC) remains elusive; we were eager to resolve the questions.

Methods: Tumor tissues and the matched adjacent normal tissues were collected from patients with RCC. Messenger RNA (mRNA) levels of TUG1, yes‐associated protein (YAP), and microRNA (miR)‐9 levels were determined by reverse transcription quantitative polymerase chain reaction (RT‐qPCR). The regulation of YAP by TUG1 was investigated using Western blot analysis, RT‐qPCR, and immunofluorescence. The oncogenic roles of TUG1 and YAP were studied using a cell proliferation assay and a wound healing assay. The interaction of TUG1‐miR‐9‐YAP was analyzed in RCC cell lines.

Results: In the current study, we observed a positive correlation between TUG1 expression and YAP expression in RCC using the Gene Expression Omnibus database and tumor tissues collected from 58 patients with RCC. The TUG1 elevation enhanced YAP expression but did not alter the Hippo‐signaling pathway activity or YAP protein distribution in cells. In addition, we found that TUG1 could bind to miR‐9; therefore, TUG1 could positively control YAP expression via downregulation of miR‐9 level. Furthermore, we observed that inhibition of cell proliferation and cell migration induced by TUG1 silencing could be reversed by overexpression of YAP in RCC cell lines.

Conclusions: Our findings indicated a pivotal role of TUG1 in driving RCC progression via regulation of miR‐9/YAP, suggesting a potential therapeutic targeting role of TUG1 in RCC.
Docosahexaenoic acid attenuates the detrimental effect of palmitic acid on human endothelial cells by modulating genes from the atherosclerosis signaling pathway
Authors: Novinbahador Tannaz , Nourazarian Alireza , Asgharzadeh Mohammad , Rahbarghazi Reza , Avci Çıgır Biray , Bagca Bakiye Goker , Ozates Neslihan Pinar , Karbasforoush Saeede , Khaki‐Khatibi Fatemeh
Published: August 2018

The formation of atherosclerotic changes leads to dysfunction in numerous cell types, especially endothelial cells. In the current experiment, we aimed to show the therapeutic effect of Docosahexaenoic acid on palmitic‐induced atherosclerotic changes in the human endothelial lineage. Human Umbilical Vein Endothelial cells were incubated with 1 mM palmitic acid for 48 hours and then exposed to 40 µM docosahexaenoic acid for next 24 hours. Cellular atherosclerosis and lipid removal were confirmed by the application of Oil red O solution. The cell survival rate was studied by using MTT assay and flow cytometry analysis of Annexin V. We also measured the protein level of tumor necrosis factor‐α and granulocyte‐macrophage colony‐stimulating factor by immunofluorescence imaging. The transcription level of genes participating in the atherosclerosis signaling pathway was monitored in atherosclerotic endothelial cells before and after treatment with docosahexaenoic acid. The viability of the cells was reduced after 48 hours incubation with palmitic acid. It is noteworthy that the number of viable endothelial cells was increased after exposure to docosahexaenoic acid. Compared with the cells that received palmitic acid, Oil red O staining showed a decrease in the cellular content of fatty acid after incubation with docosahexaenoic acid (P < 0.05). PCR array indicated that the modulation of key genes played a role in atherosclerosis and reached near‐control levels. These data support the notion that incubation of atherosclerotic human endothelial cells with docosahexaenoic acid could return the detrimental effects of palmitic acid by modulation of the atherosclerosis signaling pathway.