bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating cancer patient–reported outcome measures: Readability and implications for clinical use
Authors: Papadakos Janet K. , Charow Rebecca C. , Papadakos Christine J. , Moody Lesley J. , Giuliani Meredith E.
Published: January 2019

Background

The benefits of patient‐reported outcome measures (PROMs) are well known; however, their readability has come into question because multiple PROMs have been found to be incomprehensible to patients. This is a critical safety and equity consideration because PROMs are increasingly being integrated into routine clinical practice. A key strategy for promoting patient comprehension is the use of plain language. The aim of this study was to determine whether PROMs routinely used in the cancer setting meet plain‐language best practices.

Methods

To report the plain‐language level of each PROM, readability (Fry Readability Graph, Simple Measure of Gobbledygook, Flesch Reading Ease, and FORCAST) and understandability assessments (Patient Education Materials Assessment Tool [PEMAT] for Printable Materials) were performed. PROMs at grade level 6 or lower and with PEMAT scores greater than 80% were considered to meet plain‐language best practices. PROMs were divided into 4 domains (physical, emotional, social, and quality of life) and 17 dimensions (eg, pain was a dimension of the physical domain). A subanalysis was conducted to determine whether specific domains and dimensions were more likely to adhere to plain‐language best practices.

Results

More than half of the 45 PROMs evaluated (n = 33 [73%]) had a grade level higher than 6. Understandability scores ranged from 29% to 100%. The majority of the PROMs that did not meet plain‐language best practices were within the physical and emotional domains and focused on the patient’s symptom experience.

Conclusions

This evaluation shows that more than half of the most commonly used cancer PROMs do not meet plain‐language best practices. Practice implications include the necessity for plain‐language assessment during the PROM validation process, the consideration of plain language in PROM selection, and plain‐language review and editing of low‐scoring PROMs.
Association between age and sex and mortality after adjuvant therapy for renal cancer
Authors: Mamtani Ronac , Wang Xin Victoria , Gyawali Bishal , DiPaola Robert S. , Epperson C. Neill , Haas Naomi B. , Dutcher Janice P.
Published: January 2019

Background

In phase 3 trials of patients with resected high‐risk renal cell carcinoma, adjuvant sunitinib has demonstrated no overall survival (OS) benefit, an uncertain disease‐free survival (DFS) benefit, and increased toxicity versus placebo. To identify patients who may derive benefit or harm from adjuvant therapy, the authors assessed the effects of age and sex on treatment outcomes in the phase 3 Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Cancer (ASSURE) trial.

Methods

The authors conducted a post hoc subgroup analysis of age and sex among patients in the ASSURE trial. Adjusted hazard ratios (HRs) for OS and DFS were evaluated with sunitinib or sorafenib versus placebo in 4 patient subgroups defined by sex and median age at the time of the study.

Results

Sunitinib treatment was associated with decreased OS (HR, 2.21; 95% confidence interval, 1.29‐3.80) among women aged >56 years, but not in women aged ≤56 years or men of any age. Similar associations with age and sex were observed for DFS, but these were not statistically significant (women aged >56 years: HR, 1.41 [95% confidence interval, 0.94‐2.10]). No such association was found for sorafenib. The interaction by age and sex on mortality was found to be statistically significant for sunitinib (P = .01), but not sorafenib (P = .10).

Conclusions

Adjuvant sunitinib may increase mortality among older women with renal cell carcinoma. Given the recent approval of adjuvant sunitinib for patients with high‐risk resected renal cell carcinoma, additional studies are needed to confirm these findings.
Improving cancer‐specific outcomes in solid organ transplant recipients: Where to begin?
Authors: Koff Jean L. , Waller Edmund K.
Published: January 2019

In an article published in this issue of Cancer, D’Arcy et al link the incidence of cancer among recipients of solid organ transplantation (SOT) in the Scientific Registry of Transplant Recipients with data from regional and statewide cancer registries to examine cancer‐specific mortality for common malignancies in SOT recipients. This analysis helps to illuminate the role of immune surveillance across a broad range of malignancies and compares the incidence of cancers due to virally mediated oncogenesis (lymphoma, squamous cell carcinoma of the aerodigestive epithelium, and hepatitis‐induced liver cancer) with the incidence of other malignancies. The authors’ central finding is that cancer‐specific mortality is significantly increased in SOT recipients in comparison with nontransplant recipients for multiple cancers, and the increased cancer incidence is not limited to the effects of viral oncogenesis. The authors document a significant increase in common epithelial malignancies that are currently treated with immune checkpoint antibodies, including melanoma, bladder cancer, colorectal cancer, cancers of the oral cavity/pharynx, kidney cancer, and lung cancer, and this supports the hypothesis that post‐SOT immunosuppression affects immune surveillance in these cancers. Provocatively, the authors also document increases in the incidence and mortality of cancers not typically responsive to immune checkpoint therapies, including breast cancer and pancreatic cancer. The findings of D’Arcy et al suggest that immune surveillance controls oncogenesis and tumor progression in a broad range of malignancies and that breast cancer and pancreatic cancer could be sensitive to drugs targeting immune surveillance pathways other than those treated with currently Food and Drug Administration–approved antibodies to CTLA4 and PD‐1/PD‐L1.
Effect of Size of Giant Component for actor node selection in WSANs: A comparison study
Authors: Elmazi Donald , Cuka Miralda , Ikeda Makoto , Barolli Leonard
Published: January 2019

Wireless Sensor and Actor Network (WSAN) is formed by the collaboration of micro‐sensor and actor nodes. Whenever there is any special event, ie, fire, earthquake, flood or enemy attack in the network, sensor nodes have responsibility to sense it and send information towards an actor node. The actor node is responsible to take prompt decision and react accordingly. In this work, we propose and implement two Fuzzy Based Systems (FBS): FBS1 and FBS2 for actor selection in WSANs. Different from FBS1, in FBS2, we added the Size of Giant Component (SGC) as new parameter. The systems decide whether the actor will be selected for the required job or not, based on data supplied by sensors and actual actor condition. We evaluated the proposed system by computer simulations. Comparing FBS1 with FBS2, we can see that SGC parameter that is used in FBS2 gives to the system a better performance due to the growth of SGC parameter.
Interactions of Hydrogen with Pd@MOF Composites
Authors: Malouche Abdelmalek , Zlotea Claudia , Szilágyi Petra Ágota
Published: January 2019

Physisorption and chemisorption of hydrogen on solid‐state materials are two fundamentally different interactions, both of which display advantages and drawbacks for hydrogen storage. It has been hypothesised that their combination by merging two classes of materials showing different sorption behaviour towards hydrogen in the same composite may synergistically combine their desirable properties. As representatives of such composites, palladium nanoparticles, nanoclusters, and single atoms have been encapsulated in a metal‐organic framework matrix, embedded, or immobilised in its pores, respectively. In this minireview, we review advances on the understanding and potential applications of the combination of Pd with metal‐organic framework matrices through the analysis of the nanocomposite materials’ interaction with hydrogen and sorption properties.
Liberating Native Mass Spectrometry from Dependence on Volatile Salt Buffers by Use of Gábor Transform
Authors: Cleary Sean P. , Prell James S.
Published: January 2019

Volatile salts, such as ammonium acetate, are commonly used in buffers for the analysis of intact proteins and protein complexes in native electrospray ionization mass spectrometry. Although these solutions are not technically buffers near pH 7, the volatile nature of the salt minimizes ion adduction to proteins upon transfer to vacuum. Conversely, common biochemical salt buffers, such as Tris/NaCl, are not traditionally used in native mass spectrometry because of the tendency of sodium and other ions to adduct to proteins or form large cluster ions, severely frustrating accurate mass assignment. Here, we demonstrate a Gábor transform method for extracting signal from native‐like protein ions even in the presence of a large salt‐cluster background. We further show the utility of this method in characterizing polymers and show that the measured average mass of long‐chain polyethylene glycol ions from a commercial polymer sample is ∼30 % higher than the manufacturer‐estimated average mass. It is expected that this method will enable more widespread use of conventional biochemical buffers in native mass spectrometry and decrease dependence on volatile salts.
Grafting Copper and Gallium Corroles onto Zinc Oxide Nanoparticles
Authors: Berionni Berna Beatrice , Savoldelli Andrea , Pomarico Giuseppe , Zurlo Francesca , Magna Gabriele , Paolesse Roberto , Fronczek Frank R. , Smith Kevin M. , Nardis Sara
Published: January 2019

Two different copper and gallium arylcorroles have been functionalized using the Vilsmeier–Haack reaction. A further Knoevenagel reaction with cyanoacetic acid was performed on both complexes, affording the desired products with yields above 90 %. The newly synthesized compounds have been thoroughly characterized by a combination of spectroscopic methods, optical analyses, and X‐ray crystallography. Moreover, they have been tested as anchoring groups for the hydrothermal synthesis of ZnO nanoparticles. The morphology of the heterogeneous composites has been studied by SEM, EDS and fluorescence microscopy analyses, thus confirming the presence of the corrole macrocycle in the hybrid material.
Nuclear FGFR2 regulates musculoskeletal integration within the developing limb
Authors: Salva Joanna E. , Roberts Ryan R. , Stucky Taylor S. , Merrill Amy E.
Published: January 2019

Background

Bent bone dysplasia syndrome (BBDS), a congenital skeletal disorder caused by dominant mutations in fibroblast growth factor receptor 2 (FGFR2), is characterized by bowed long bones within the limbs. We previously showed that the FGFR2 mutations in BBDS enhance nuclear and nucleolar localization of the receptor; however, exactly how shifts in subcellular distribution of FGFR2 affect limb development remained unknown.

Results

Targeted expression of the BBDS mutations in the lateral plate mesoderm of the developing chick induced angulated hindlimbs, a hallmark feature of the disease. Whole‐mount analysis of the underlying skeleton revealed bent long bones with shortened bone collars and, in severe cases, dysmorphic epiphyses. Epiphyseal changes were also correlated with joint dislocations and contractures. Histological analysis revealed that bent long bones and joint defects were closely associated with irregularities in skeletal muscle patterning and tendon‐to‐bone attachment. The spectrum of limb phenotypes induced by the BBDS mutations were recapitulated by targeted expression of wild‐type FGFR2 appended with nuclear and nucleolar localization signals.

Conclusions

Our results indicate that the bent long bones in BBDS arise from disruptions in musculoskeletal integration and that increased nuclear and nucleolar localization of FGFR2 plays a mechanistic role in the disease phenotype. 248:233‐246, 2019. © 2018 Wiley Periodicals, Inc.
Embryological development of Salvator merianae (Squamata: Teiidae)
Authors: Iungman Josefina L. , Molinero María N. , Simoncini Melina S. , Piña Carlos I.
Published: January 2019

Here we describe the embryonic development of Salvator merianae external morphologic features, as based on observation of 28 embryos across different days of incubation at 31 ± 0.5°C. Observed developmental stages were grouped and classified into the early, middle, and late periods. The early period (Stages 3–11) is distinguished by the origin of the encephalic vesicles, sensory placodes, pharyngeal arches, and degree of body flexion and rotation. The medium period (Stages 8–15) is distinguished by limb differentiation and by cranium‐facial characteristics. The late period (Stages 15–18) is determined by scale patterns, pigmentation, and embryo growth.
Spatial ecology of a range‐expanding bumble bee pollinator
Authors: Crowther Liam P. , Wright David J. , Richardson David S. , Carvell Claire , Bourke Andrew F. G.
Published: January 2019

Molecular methods have greatly increased our understanding of the previously cryptic spatial ecology of bumble bees (Bombus spp.), with knowledge of the spatial ecology of these bees being central to conserving their essential pollination services. Bombus hypnorum, the Tree Bumble Bee, is unusual in that it has recently rapidly expanded its range, having colonized much of the UK mainland since 2001. However, the spatial ecology of B. hypnorum has not previously been investigated. To address this issue, and to investigate whether specific features of the spatial ecology of B. hypnorum are associated with its rapid range expansion, we used 14 microsatellite markers to estimate worker foraging distance, nest density, between‐year lineage survival rate and isolation by distance in a representative UK B. hypnorum population. After assigning workers to colonies based on full or half sibship, we estimated the mean colony‐specific worker foraging distance as 103.6 m, considerably less than values reported from most other bumble bee populations. Estimated nest density was notably high (2.56 and 0.72 colonies ha−1 in 2014 and 2015, respectively), estimated between‐year lineage survival rate was 0.07, and there was no evidence of fine‐scale isolation by distance. In addition, genotyping stored sperm dissected from sampled queens confirmed polyandry in this population (mean minimum mating frequency of 1.7 males per queen). Overall, our findings establish critical spatial ecological parameters and the mating system of this unusual bumble bee population and suggest that short worker foraging distances and high nest densities are associated with its rapid range expansion.
Accuracy improvement of functional attribute recognition by dense CRF considering object shape
Authors: Iizuka Masaki , Akizuki Shuichi , Hashimoto Manabu
Published: January 2019

In this paper, we propose a method to recognize functional attributes of everyday objects for vision system of partner robots. On the related research, there is a method to optimize recognition result with dense (fully connected) conditional random field (CRF), which uses the estimation result of functional attribute for each pixel. However, since this method is optimized from RGB data, it is not able to sufficiently consider the shape of object, which has a relationship with the function attribute. In the proposed method, the recognition accuracy of functional attributes is improved by considering the object shape with the dense CRF describing the three‐dimensional positional relationship. As a result of the experiment, the recognition rate of the proposed method is 77.0%, which is 3.8% higher than the related method. In addition, we confirmed that the processing speed is high as a side effect by reducing processing cost by oversegmentation of input data and using high‐speed identification by Random Forests. The mean processing speed per an object was 109 ms in the proposed method.
Temporal variation in resource selection of African elephants follows long‐term variability in resource availability
Authors: Tsalyuk Miriam , Kilian Werner , Reineking Björn , Getz Wayne Marcus
Published: January 2019

The relationship between resource availability and wildlife movement patterns is pivotal to understanding species behavior and ecology. Movement response to landscape variables occurs at multiple temporal scales, from sub‐diurnal to multiannual. Additionally, individuals may respond to both current and past conditions of resource availability. In this paper, we examine the temporal scale and variation of current and past resource variables that affect movement patterns of African elephants (Loxodonta africana) using sub‐hourly movement data fromGPS‐GSMcollared elephants in Etosha National Park, Namibia. We created detailed satellite‐based spatiotemporal maps of vegetation biomass, as well as distance from surface water, road and fence. We used step selection functions to measure the relative importance of these landscape variables in determining elephants’ local movement patterns. We also examined how elephants respond to information, in locations they have previously visited, on productivity integrated over different temporal scales: from current to historical conditions. Our results demonstrate that elephants choose patches with higher than average annual productivity and grass biomass, but lower tree biomass. Elephants also prefer to walk close to water, roads, and fences. These preferences vary with time of day and with season, thereby providing insights into diurnal and seasonal behavioral patterns and the ecological importance of the landscape variables examined. We also discovered that elephants respond more strongly to long‐term patterns of productivity than to immediate forage conditions, in familiar locations. Our results illustrate how animals with high cognitive capacity and spatial memory integrate long‐term information on landscape conditions. We illuminate the importance of long‐term high temporal resolution satellite imagery to understanding the relationship between movement patterns and landscape structure.
Carcinoid heart disease involving the left heart: a case report and biomarker analysis
Authors: Lichtenauer Michael , Pichler Tristan , Eder Sarah , Mirna Moritz , Magnes Theresa , Wernly Bernhard , Paar Vera , Jung Christian , Prinz Erika , Seitelberger Rainald , Hoppe Uta C.
Published: January 2019

Herein, we report the case of a 67‐year‐old woman who was admitted to our hospital because of dyspnoea and oedema of the lower extremities. Transthoracic echocardiography revealed severe tricuspid and mitral regurgitation, and the leaflets of the tricuspid valve were found to be rigid and almost immobile. The plasma concentrations of serotonin and chromogranin A were elevated, and hence, suspicion for carcinoid heart disease was raised. In addition to the diagnostic workup and medical and surgical treatment, we analysed levels of novel cardiovascular biomarkers throughout the entire follow‐up by means of enzyme‐linked immunosorbent assay. A dopa positron emission tomography (DOPA‐PET) was conducted and showed a neoplasm in the terminal ileum. Tricuspid valve replacement, mitral valve repair, and a closure of the patent foramen ovale (PFO) were conducted. Two months later, hemicolectomy and liver segment resection were performed. The tumour was resected, and the diagnosis of a neuroendocrine tumour (NET) was confirmed. Throughout the follow‐up, we observed a decrease in the plasma levels of novel biomarkers [e.g. interleukin‐8 (IL‐8), soluble suppression of tumorigenicity‐2 (sST2), and heart‐type fatty acid‐binding protein (H‐FABP)] over the follow‐up period. In our case, carcinoid heart disease resulted in a severe tricuspid regurgitation as commonly seen in these patients. Moreover, a pre‐existent mitral regurgitation was likely aggravated by fibrotic remodelling, because a PFO has led to a right‐to‐left shunt and might have caused left heart involvement. As IL‐8 was associated with adverse outcomes in patients with NETs, and sST2 and H‐FABP were associated with adverse outcomes in patients with heart failure previously, these biomarkers could aid in the risk stratification of patients with NET.
Risk factors for incident heart failure in age‐ and sex‐specific strata: a population‐based cohort using linked electronic health records
Authors: Uijl Alicia , Koudstaal Stefan , Direk Kenan , Denaxas Spiros , Groenwold Rolf H. H. , Banerjee Amitava , Hoes Arno W. , Hemingway Harry , Asselbergs Folkert W.
Published: January 2019

Aims

Several risk factors for incident heart failure (HF) have been previously identified, however large electronic health records (EHR) datasets may provide the opportunity to examine the consistency of risk factors across different subgroups from the general population.

Methods and results

We used linked EHR data from 2000 to 2010 as part of the UK‐based CALIBER resource to select a cohort of 871 687 individuals 55 years or older and free of HF at baseline. The primary endpoint was the first record of HF from primary or secondary care. Cox proportional hazards analysis was used to estimate hazard ratios for associations between risk factors and incident HF, separately for men and women and by age category: 55–64, 65–74, and > 75 years. During 5.8 years of median follow‐up, a total of 47 987 incident HF cases were recorded. Age, social deprivation, smoking, sedentary lifestyle, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, body mass index, haemoglobin, total white blood cell count and creatinine were associated with HF. Smoking, atrial fibrillation and diabetes showed stronger associations with incident HF in women compared to men.

Conclusion

We confirmed associations of several risk factors with HF in this large population‐based cohort across age and sex subgroups. Mainly modifiable risk factors and comorbidities are strongly associated with incident HF, highlighting the importance of preventive strategies targeting such risk factors for HF.
Rhodium(I)‐α‐Phenylvinylfluorenyl Complexes: Synthesis, Characterization, and Evaluation as Initiators in the Stereospecific Polymerization of Phenylacetylene
Authors: Tan Nicholas Sheng Loong , Simpson Peter V. , Nealon Gareth L. , Sobolev Alexandre N. , Raiteri Paolo , Massi Massimiliano , Ogden Mark I. , Lowe Andrew B.
Published: January 2019

The synthesis, characterization and use, as initiators for phenylacetylene polymerizations, of three new rhodium(I)‐vinyl complexes containing fluorenyl functionality with fluorine‐functionalized phosphine ligands is described. Rh(nbd)(CPh=CFlu)P(4‐FC6H4)3, Rh(nbd)(CPh=CFlu)P(4‐CF3C6H4)3, and Rh(nbd)(CPh=CFlu)P[3,5‐(CF3)2C6H3]3 (nbd: 2,5‐norbornadiene; Flu: fluorenyl) were prepared and isolated as discrete, orange compounds and were readily recrystallized yielding X‐ray quality crystals. All complexes were characterized by a combination of 1H, 31P, 19F, 103Rh NMR spectroscopy and 2D 31P‐103Rh/31P‐103Rh{103Rh} heteronuclear multiple‐quantum correlation (HMQC) experiments, elemental analysis, and single‐crystal X‐ray analysis. The complexes were active as initiators in the co‐ordination insertion polymerization of phenylacetylene, with initiation efficiencies spanning the range 13–56 %, and yielded polyphenylacetylenes of low dispersity (Ð = Mw/Mn) with high cis‐transoidal stereoregularity.
Construction of Di(hetero)arylmethanes Through Pd‐Catalyzed Direct Dehydroxylative Cross‐Coupling of Benzylic Alcohols and Aryl Boronic Acids Mediated by Sulfuryl Fluoride (SO2F2)
Authors: Zhao Chuang , Zha Gao‐Feng , Fang Wan‐Yin , Rakesh K. P. , Qin Hua‐Li
Published: January 2019

A practical Pd‐catalyzed direct dehydroxylative coupling of (hetero)benzylic alcohols with (hetero)arylboronic acids for the constructions of di(hetero)arylmethane derivatives under SO2F2 was described. This new method provided a strategically distinct approach to di(hetero)arylmethane derivatives from readily available and abundant benzylic alcohols under mild condition.
Spatially filtered unconditional quantile regression: Application to a hedonic analysis
Authors: Murakami D. , Seya H.
Published: January 2019

Unconditional quantile regression (UQR) attracts attention in various fields to investigate the impacts of explanatory variables on quantiles of the marginal distribution of an explained variable. This study attempts to introduce spatial dependence into the UQR within the framework of random effects eigenvector spatial filtering, resulting in the model that we term the spatially filtered UQR (SF‐UQR). We then develop a computationally efficient approach for SF‐UQR estimation. Finally, the performance of the SF‐UQR is tested with a hedonic land price model for the Tokyo metropolitan area. SF‐UQR is implemented in an R package, “spmoran.”
Zircon U–Pb, O isotope, and geochemistry study of the early Palaeozoic granitic gneiss in the Dinggye district, central Himalaya: Implications for the early Palaeozoic orogenic event along the northern margin of Gondwana
Authors: Zhang Fan , Wang Yanbin , Yang Deting
Published: January 2019

To better constrain the evolution of the early Palaeozoic orogenesis along the northern margin of Gondwana, we present new petrological, geochronological, and geochemical studies of the Cambrian–Ordovician granitic gneiss in the Dinggye area, central Himalaya. The granitic gneiss is medium‐coarse grained, with porphyritic, augen, banded, or gneissic structure, and has undergone strong deformation. The mineral assemblages are quartz, plagioclase, K‐feldspar, muscovite, and biotite, with minor amounts of accessory minerals. The granitic gneiss samples are characterized by high SiO2, Al2O3, and Rb/Sr contents but low MgO, TiO2, FeOt, and MnO contents, with A/CNK of 1.08–1.38. The REE patterns of the granitic gneiss show high LREE/HREE and negative Eu anomalies. In the trace‐element chondrite‐normalized diagram, the samples show enrichment in LILE (e.g., Rb, Th, U, and K) and depletion in some HFSEs (Nb and Ti). These features indicate that the protolith was a calc‐alkaline and peraluminous S‐type granite. Six analysed samples yielded zircon U–Pb crystallization ages between 480 and 500 Ma, which support the existence of the early Palaeozoic magmatism in the Dinggye area, central Himalaya. High δ18O values (7–10‰, >> a mantle value of 5.3 ± 0.6‰) of magmatic zircon domains and abundant inherited zircons with variable ages (558‐2523 Ma) indicate that the magma was derived from a supracrustal source. Combined with whole‐rock Sr–Nd data (average εNd(t) = −8.1) published previously, we suggest that the granitic gneiss originated from partial melting of old crust, most likely to be the sedimentary rocks of the Himalayan Crystalline Complex. The early Palaeozoic granitic gneiss with a continental arc affinity may have formed in an Andean‐type orogeny involving subduction of the Proto‐Tethyan Oceanic crust beneath the northern margin of the Gondwana supercontinent.
The K2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration
Authors: Albrecht Stefanie , Korr Sabrina , Nowack Luise , Narayanan Venu , Starost Laura , Stortz Franziska , Araúzo‐Bravo Marcos J. , Meuth Sven G. , Kuhlmann Tanja , Hundehege Petra
Published: January 2019

In multiple sclerosis, demyelination occurs as a consequence of chronic autoimmunity in the central nervous system causing progressive neurological impairment in patients. After a demyelinating event, new myelin sheaths are formed by adult oligodendroglial progenitor cells; a process called remyelination. However, remyelination often fails in multiple sclerosis due to insufficient recruitment and differentiation of oligodendroglial precursor cells. A pivotal role for the two‐pore‐domain potassium (K2P) channel, TASK1, has already been proven for an animal model of multiple sclerosis. However, the mechanisms underlying the TASK1‐mediated effects are still elusive. Here, we tested the role of TASK1 channels in oligodendroglial differentiation and remyelination after cuprizone‐induced demyelination in male mice. We found TASK1 channels to be functionally expressed on primary murine and human, pluripotent stem cell‐derived oligodendrocytes. Lack of TASK1 channels resulted in an increase of mature oligodendrocytes in vitro as well as a higher number of mature oligodendrocytes and accelerated developmental myelination in vivo. Mechanistically, Task1‐deficient cells revealed a higher amount of phosphorylated WNK1, a kinase known to be involved in the downstream signaling of the myelination regulator LINGO‐1. Furthermore, we analyzed the effect of genetic TASK1 ablation or pharmacological TASK1 inhibition on disease‐related remyelination. Neither channel inhibition nor lack of TASK1 channels promoted remyelination after pathological demyelination. In summary, we conclude that functional TASK1 channels participate in the modulation of differentiating oligodendroglial cells in a previously unknown manner. However, while being involved in developmental myelination our data suggest that TASK1 channels have no major effect on remyelination.
Histopathological features of juvenile‐onset laryngeal papillomatosis related to severity
Authors: El Achkar Vivian Narana Ribeiro , Duarte Andressa , Carlos Román , León Jorge Esquiche , Ribeiro‐Silva Alfredo , Pignatari Shirley Shizue Nagata , Kaminagakura Estela
Published: January 2019

Background

Laryngeal papillomatosis (LP) is a disease that presents in both juvenile (JLP) and adult patients (ALP). This study correlated papillomatosis characteristics with the Derkay score.

Methods

Retrospective data and biopsies of 36 patients with JLP and 56 with ALP were collected and separated into groups according to their scores.

Results

The mean of the Derkay score, in the JLP group was 10.97 and in Group ALP was 8.26. The JLP group presented a more aggressive result than in the adult group (P = .02). In the JLP group, the respiratory difficulty (P = .01) and tracheostomy were correlated to a higher Derkay score (P < .05). Microscopically, the JLP samples presented a higher incidence of atypical mitosis and mitosis above the basal cells layer of the epithelium (P < .05) and these characteristics were correlated with a higher Derkay index (P = .03).

Conclusion

Findings suggest that ALP and JLP can present different clinical courses and histopathological features. There was a higher degree of LP severity in JLP.
Targeted RNA‐seq successfully identifies normal and pathogenic splicing events in breast/ovarian cancer susceptibility and Lynch syndrome genes
Authors: Brandão Rita D. , Mensaert Klaas , López‐Perolio Irene , Tserpelis Demis , Xenakis Markos , Lattimore Vanessa , Walker Logan C. , Kvist Anders , Vega Ana , Gutiérrez‐Enríquez Sara , Díez Orland ,   KConFaB Investigators, de la Hoya Miguel , Spurdle Amanda B. , De Meyer Tim , Blok Marinus J.
Published: January 2019

A subset of genetic variants found through screening of patients with hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome impact RNA splicing. Through target enrichment of the transcriptome, it is possible to perform deep‐sequencing and to identify the different and even rare mRNA isoforms. A targeted RNA‐seq approach was used to analyse the naturally‐occurring splicing events for a panel of 8 breast and/or ovarian cancer susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, PTEN, STK11, CDH1, TP53), 3 Lynch syndrome genes (MLH1, MSH2, MSH6) and the fanconi anaemia SLX4 gene, in which monoallelic mutations were found in non‐BRCA families. For BRCA1, BRCA2, RAD51C and RAD51D the results were validated by capillary electrophoresis and were compared to a non‐targeted RNA‐seq approach. We also compared splicing events from lymphoblastoid cell‐lines with those from breast and ovarian fimbriae tissues. The potential of targeted RNA‐seq to detect pathogenic changes in RNA‐splicing was validated by the inclusion of samples with previously well characterized BRCA1/2 genetic variants. In our study, we update the catalogue of normal splicing events for BRCA1/2, provide an extensive catalogue of normal RAD51C and RAD51D alternative splicing, and list splicing events found for eight other genes. Additionally, we show that our approach allowed the identification of aberrant splicing events due to the presence of BRCA1/2 genetic variants and distinguished between complete and partial splicing events. In conclusion, targeted‐RNA‐seq can be very useful to classify variants based on their putative pathogenic impact on splicing.
Therapeutic thrombocytapheresis for extreme thrombocytosis after chemotherapy in essential thrombocytosis
Authors: Almeida‐Dias Raquel , Garrote Marta , Cid Joan , Mustieles Maria‐Jesús , Alba Cristina , Lozano Miquel
Published: January 2019

Essential thrombocytosis (ET) is a chronic myeloproliferative neoplasm characterized by the presence of thrombocytosis and it can be complicated by thrombotic and/or hemorrhagic events. Treatment options include low‐dose aspirin and cytoreductive agents such as hydroxyurea. In cases of extreme thrombocytosis, therapeutic thrombocytapheresis can be a useful procedure. We present a case of a 61‐year‐old‐man previously diagnosed with CALR‐mutated ET, who develop acute myeloid leukemia. When recovering after induction chemotherapy, he developed an extreme thrombocytosis up to 2337 × 109/L regardless hydroxyurea was started. Two therapeutic trombocytapheresis were performed and anagrelide was added to cytoreductive regimen. Platelet count stabilized around 570 × 109/L. Both procedures were performed with the Spectra Optia Apheresis System version 11.3 (Terumo BCT) and we decided to use a higher collection preference and lower collection speed than manufacturer's recommendations. Platelet count decreased from 2380 × 109/L to 1035 × 109/L in the first procedure and from 1813 × 109/L to 768 × 109 in the second procedure. Platelet collection efficiency was calculated to be 110.3% and 86.1% in the first and second thrombocytapheresis, respectively. Therapeutic thrombocytapheresis with Spectra Optia is a safe and efficient therapy to treat patients with primary thrombocytosis while effect of cytoreductive agents is attained. Platelet collection efficiency was calculated to be higher than previously reported. We suggest that changes in technical parameters such as a deeper aspiration point and/or lower collection speed may increase procedure's efficiency.
Multiracial Identity, Color‐Blind Racial Ideology, and Discrimination: Professional Counseling Implications
Authors: McDonald C. Peeper , Chang Catherine Y. , Dispenza Franco , O’Hara Caroline
Published: January 2019

Because of the expansive multiracial population growth in the United States, the authors explored multiracial identity integration (MII), color‐blind racial ideology (CBRI), and discrimination using regression analyses with 288 individuals. CBRI and discrimination significantly correlated and predicted MII, with 15.3% of the variance explained by discrimination and CBRI. Moderation analysis revealed that CBRI did not moderate the relationship between discrimination and MII. Continued research among multiracial individuals is recommended to better understand the CBRI and racial identity link.
Challenges and Coping Mechanisms of Whites Committed to Antiracism
Authors: Malott Krista M. , Schaefle Scott , Paone Tina R. , Cates Jennifer , Haizlip Breyan
Published: January 2019

Scholars have cited an antiracist identity as an ideal development status for Whites seeking to change systemic racism (Helms, 1995). However, little is known regarding the lived complexities of antiracist work itself. This article examines the experiences of one group of Whites (N = 10) committed to antiracist action. Outcomes indicate challenges that include backlash and struggles to identify more effective antiracist tactics. Coping mechanisms are considered in relation to counseling and counselor training practices.
Downregulation of HDAC2 and HDAC3 via oleuropein as a potent prevention and therapeutic agent in MCF‐7 breast cancer cells
Authors: Bayat Sahar , Mansoori Derakhshan Sima , Mansoori Derakhshan Neda , Shekari Khaniani Mahmoud , Alivand Mohammad Reza
Published: January 2019

Breast cancer is the most common malignancy in the world with the highest rate of morbidity and mortality. Due to the several side effects of chemotherapy and radiotherapy, recent studies have focused on the use of herbal medicines. Epidemiological reports have shown the inverse relationship between breast cancer risk and intake of olive. Oleuropein (OLE) is a polyphenolic compound in virgin olive oil with antineoplastic properties and it is well tolerated by humans. Recent reports have shown that OLE has effects on the control of cancer by modulating epigenetics, such as histone deacetylase (HDAC) inhibition. However, the epigenetic mechanisms of OLE anticancer properties are yet to be properly investigated. Therefore, this study aimed to determine the therapeutic effects of OLE through the modulation of histone deacetylase 2 (HDAC2) and histone deacetylase 3 (HDAC3) expression in breast cancer cell line. MCF‐7 cells were tested with and without OLE, and also the cell viability, apoptosis, and migration were examined. HDAC2 and HDAC3 expression genes were assessed by quantitative real‐time polymerase chain reaction. It was found that OLE decreased the expression of both HDAC2 and HDAC3 (P < 0.05), induced apoptosis and retarded cell migration and cell invasion in a dose‐dependent manner (P < 0.05). These results showed that OLE is a potential therapeutic and preventive agent for breast cancer.
Long noncoding RNA Linc00339 promotes triple‐negative breast cancer progression through miR‐377‐3p/HOXC6 signaling pathway
Authors: Wang Xiaolong , Chen Tong , Zhang Yan , Zhang Ning , Li Chen , Li Yaming , Liu Ying , Zhang Hanwen , Zhao Wenjing , Chen Bing , Wang Lijuan , Yang Qifeng
Published: January 2019

Recently, long noncoding RNAs (lncRNAs) have become the key gene regulators and prognostic biomarkers in various cancers. Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The effects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays were applied to evaluate the functions of Linc00339, miR‐377‐3p, and HOXC6 on cell proliferation. Flow cytometry analysis was used to detect apoptosis and cell cycle distribution. Overall survival (OS) was analyzed using data from The Cancer Genome Atlas and molecular taxonomy of breast cancer international consortium (METABRIC). Dual luciferase assay and RNA immunoprecipitation were performed to confirm the interaction between Linc003339 and miR‐377‐3p. Linc00339 was increased in breast cancer cell lines compared with the normal epithelial cell. Through in vitro and in vivo experiments, Linc00339 overexpression promoted triple‐negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis. Silencing of Linc00339 obtained the opposite effects. Mechanistic investigations demonstrated that Linc00339 could sponge miR‐377‐3p and regulate its expression. Higher expression of miR‐377‐3p indicated longer OS in breast cancer patients, especially in TNBC patients. Overexpression of miR‐377‐3p retarded TNBC cell growth through regulating cell cycle distribution and apoptosis. And miR‐377‐3p was involved in Linc00339‐mediated TNBC proliferation through regulating HOXC6 expression. Knockdown of HOXC6 inhibited TNBC progression. In conclusion, our results illuminated that the novel Linc00339/miR‐377‐3p/HOXC6 axis played a critical role in TNBC progression and might be a promising therapeutic target for TNBC treatment.
The phosphoinositide hydrolase phospholipase C delta1 inhibits epithelial‐mesenchymal transition and is silenced in colorectal cancer
Authors: Xiang Qin , He Xiaoqian , Mu Junhao , Mu Haixi , Zhou Dishu , Tang Jun , Xiao Qian , Jiang Yu , Ren Guosheng , Xiang Tingxiu , Peng Weiyan
Published: January 2019

In this study, we found that the phospholipase C delta1 (PLCD1) protein expression is reduced in colorectal tumor tissues compared with paired surgical margin tissues. PLCD1‐promoted CpG methylation was detected in 29/64 (45%) primary colorectal tumors, but not in nontumor tissues. The
PLCD1 RNA expression was also reduced in three out of six cell lines, due to PLCD1 methylation. The ectopic expression of
PLCD1 resulted in inhibited proliferation and attenuated migration of colorectal tumor cells, yet promoted colorectal tumor cell apoptosis in vitro. We also observed that PLCD1 suppressed proliferation and promoted apoptosis in vivo. In addition,
PLCD1 induced G1/S phase cell cycle arrest. Furthermore, we found that PLCD1 led to the downregulation of several factors downstream of β‐catenin, including c‐Myc and cyclin D1, which are generally known to be promoters of tumorigenesis. This downregulation was caused by an upregulation of E‐cadherin in colorectal tumor cells. Our findings provide insights into the role of
PLCD1 as a tumor suppressor gene in colorectal cancer (CRC), and demonstrate that it plays significant roles in proliferation, migration, invasion, cell cycle progression, and epithelial‐mesenchymal transition. On the basis of these results, tumor‐specific methylation of PLCD1 could be used as a novel biomarker for early detection and prognostic prediction in CRC.
S1P mediates human amniotic cells proliferation induced by a 50‐Hz magnetic field exposure via ERK1/2 signaling pathway
Authors: Qiu Liping , Chen Liangjing , Yang Xiaobo , Ye Anfang , Jiang Wei , Sun Wenjun
Published: January 2019

Extremely low frequency electromagnetic field (ELF‐EMF) is a kind of physical stimulus in public and occupational environment. Numerous studies have indicated that exposure of cells to ELF‐EMF could promote cell proliferation. But the detailed mechanisms implicated in these proliferative processes remain unclear. In the present experiment, the possible roles of sphingosine‐1‐phosphate (S1P) in 50‐Hz magnetic field (MF)‐induced cell proliferation were investigated. Results showed that exposure of human amniotic (FL) cells to a 50‐Hz MF with an intensity of 0.4 mT significantly enhanced ceramide metabolism, increased S1P production, activated extracellular signal regulated kinase 1/2 (ERK1/2), and promoted cell proliferation. All of these effects induced by MF exposure could be inhibited by SKI II, an inhibitor of sphingosine kinase (SphK). In addition, both the cell proliferative response and the ERK1/2 activation induced by MF exposure were blocked completely by U0126, a specific inhibitor of MEK (ERK kinases 1 and 2). Taken together, the findings in present study suggested that S1P mediated 50‐Hz MF‐induced cell proliferation via triggering ERK1/2 signal pathway.
Overexpression of RNF187 induces cell EMT and apoptosis resistance in NSCLC
Authors: Fu Zhongming , Yu Wanjun , Wang Huaying , Chen Xiaofei
Published: January 2019

Overexpression of RING finger protein 187 (RNF187) was recently revealed to be a driver of several cancers. However, the expression and function of RNF187 in non–small‐cell lung cancer (NSCLC) are still unknown. Here, we uncovered that RNF187 expression was significantly higher in NSCLC samples than in matched normal lung samples at both the messenger RNA (3.55 ± 0.79 vs. 1.74 ± 0.63) and protein (2.85 ± 0.14 vs. 1.24 ± 0.02) levels. By downregulating or upregulating RNF187 expression in NSCLC cells, we showed that elevated RNF187 expression distinctly enhanced the migration, invasion, and colony formation of NSCLC cells. Moreover, we revealed that high level of RNF187 promoted NSCLC progression by inducing cell epithelial to mesenchymal transition (EMT) and apoptosis resistance mainly via activating the mitogen‐activated protein kinase and PI3K signaling. Clinically, we demonstrated that RNF187 expression was positively associated with advanced TNM stage (p = 1.29 × 10
−6), lymph node metastasis (
p = 2.69 × 10
−9), and large tumor size (
p = 0.002). Importantly, NSCLC patients with elevated RNF187 expression related to the short overall survival rate(
p = 1.29, E‐7) and could serve as an independent prognostic factor in NSCLC patients. Thus, elevated RNF187 expression promotes NSCLC development by inducing cell EMT and apoptosis resistance, and RNF187 may be a novel prognostic indicator for NSCLC patients after curative resection.
Potential use of melatonin in skin cancer treatment: A review of current biological evidence
Authors: Pourhanifeh Mohammad Hossein , Mahdavinia Mostafa , Reiter Russel J. , Asemi Zatollah
Published: January 2019

Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti‐inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor‐erythroid 2 p45‐related factor 2 and others. Thus, adding melatonin to chemo‐ and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients.
Tuning the structural properties of CeO2 by Pr and Fe codoping for enhanced visible‐light catalytic activity
Authors: Wen Weijie , Lou Zhencheng , Chen Yanjin , Chen Dingsheng , Tian Shuanghong , Xiong Ya
Published: January 2019

BACKGROUND

Iron (Fe)3+ has much a smaller ion radius than cerium (Ce)4+ but praseodymium (Pr) ions have a similar radius to Ce ions with the same valence. Hence, it is interesting to tune the structural properties, including lattice deformation, band gap and oxygen vacancy (Ov), of CeO2 by Pr and Fe codoping for enhanced visible‐light catalytic activity.

RESULTS

A series of Ce1‐x‐yPrxFeyO2‐σ (x = 0∼0.012, y = 0.003∼0.031) nanoparticles were prepared by a simple one‐step sol‐gel method. The structural properties of CeO2, including crystal deformation (cell lattice from 5.4069 to 5.4195), band gap (from 2.20 to 2.93), oxygen vacancies (Ov from 0.15% to 9.03%), and peroxide species (O22− from 0.37% to 1.09%) can be finely tuned by Pr and Fe codoping. Among ten samples, Ce0.982Pr0.003Fe0.015O2‐σ with proper structural properties showed the highest photocatalytic activity towards the degradation of acid orange 7. The first reaction rate constant reaches 0.0687 min−1, 9.3 and 7.7 times that of Ce0.994Pr0.006O2‐σ and Ce0.985Fe0.015O2‐σ, respectively. The mechanism was found to involve ·OH, ·O2− and photogenerated holes.

CONCLUSION

The structural properties of CeO2 can be finely and easily tuned by Pr and Fe codoping. Thus, the photocatalytic activity of CeO2 under visible light irradiation was boosted. © 2019 Society of Chemical Industry