bluuebunny/crossref_metadata_2025 huggingface dataset:
The central role of disgust in disorders of food avoidance
Authors: Harris Adrianne A. , Romer Adrienne L. , Hanna Eleanor K. , Keeling Lori A. , LaBar Kevin S. , Sinnott‐Armstrong Walter , Strauman Timothy J. , Wagner Henry Ryan , Marcus Marsha D. , Zucker Nancy L.
Published: February 2019

Background

Individuals with extreme food avoidance such as Avoidant Restrictive Food Intake Disorder (ARFID) experience impairing physical and mental health consequences from nutrition of insufficient variety or/and quantity. Identifying mechanisms contributing to food avoidance is essential to develop effective interventions. Anxiety figures prominently in theoretical models of food avoidance; however, there is limited evidence that repeated exposures to foods increases approach behavior in ARFID. Studying disgust, and relationships between disgust and anxiety, may offer novel insights, as disgust is functionally associated with avoidance of contamination from pathogens (as may occur via ingestion) and is largely resistant to extinction.

Method

This exploratory, cross‐sectional study included data from 1,644 adults who completed an online questionnaire. Participant responses were used to measure ARFID classification, picky eating, sensory sensitivity, disgust, and anxiety. Structural equation modeling tested a measurement model of latent disgust and anxiety factors as measured by self‐reported frequency of disgust and anxiety reactions. Mediational models were used to explore causal ordering.

Results

A latent disgust factor was more strongly related to severity of picky eating (B ≈ 0.4) and ARFID classification (B ≈ 0.6) than the latent anxiety factor (B ≈ 0.1). Disgust partially mediated the association between anxiety and picky eating and fully mediated the association between anxiety and ARFID. Models testing the reverse causal ordering demonstrated poorer fit. Findings suggest anxiety may be associated with food avoidance in part due to increased disgust.

Conclusions

Disgust may play a prominent role in food avoidance. Findings may inform novel approaches to treatment.
Differentiations of determinants for the community compositions of bacteria, fungi, and nitrogen fixers in various steppes
Authors: Sheng Rong , Li Ke , Zhang Wenzhao , Wang Hai , Liu Honglin , Zhu Xiaoya , Wu Hongxin , Zhang Xiaoqing , Lin Qimei , Sun Xuecheng , Tang Yafang , A Lamus , Wei Wenxue
Published: February 2019

Different types of steppes could provide heterogeneous habitat environments for underground microorganisms, but much less is known about how soil microbes fit the distinct habitats and what are the underlying mechanisms in shaping their community patterns.

We simultaneously examined the community compositions and structures of soil bacteria, fungi, and diazotrophs across desert, typical, and meadow steppes in Inner Mongolia using high‐throughput sequencing.

The results showed that soil bacteria, fungi, and diazotrophs exhibited different distribution patterns across steppe types. Although different steppes displayed obvious differences in climate conditions, plant traits, and soil properties, most of bacterial species were shared by all the steppes while only a few species were unique, indicating that the soil bacterial compositions were hardly influenced by the steppe types. Nevertheless, the habitat heterogeneity could cause shifts in the relative abundance of some bacterial groups, which resulted in significant changes in the community structure of soil bacteria across steppes. However, the fungal community compositions and structures were similar in typical and meadow steppes but that in desert steppe were significantly different. Whereas, the community compositions and structures of diazotrophs were strongly related to the steppe types. In this study, the similar parent material backgrounds of the steppe soils might be the important factor in shaping the homologous bacterial compositions. However, the variations in soil fertility, soil water repellency, and plant species across steppes would be the major driving forces in regulating the compositions and structures of fungal communities, while the diazotrophic communities would be more closely related to the changes in plant traits and soil fertility among steppes.

Our results provided evidence of habitat specificity for different microbial groups and their underlying drivers.
The plant diversity sampling design for The National Ecological Observatory Network
Authors: Barnett David T. , Adler Peter B. , Chemel Benjamin R. , Duffy Paul A. , Enquist Brian J. , Grace James B. , Harrison Susan , Peet Robert K. , Schimel David S. , Stohlgren Thomas J. , Vellend Mark
Published: February 2019

The National Ecological Observatory Network (NEON) is designed to facilitate an understanding of the impact of environmental change on ecological systems. Observations of plant diversity—responsive to changes in climate, disturbance, and land use, and ecologically linked to soil, biogeochemistry, and organisms—result in NEON data products that cross a range of organizational levels. Collections include samples of plant tissue to enable investigations of genetics, plot‐based observations of incidence and cover of native and non‐native species, observations of plant functional traits, archived vouchers of plants, and remote sensing airborne observations. Spatially integrating many ecological observations allows a description of the relationship of plant diversity to climate, land use, organisms, and substrates. Repeating the observations over decades and across the United States will iteratively improve our understanding of those relationships and allow for the testing of system‐level hypotheses as well as the development of predictions of future conditions.
The importance and challenges of detecting changes in forest mortality rates
Authors: McMahon Sean M. , Arellano Gabriel , Davies Stuart J.
Published: February 2019

Tree mortality rates determine forest health, community dynamics, and terrestrial carbon stocks. Climate change is predicted to increase global forest mortality, and some studies have observed recent changes in mortality rates. Assessing shifts in mortality and identifying their causes is challenged by the low mortality rates of trees and the limited scale at which tree mortality is typically assessed. Detecting changes in mortality and assigning mechanisms to those changes may not be feasible unless there are exceptionally large and persistent shifts in forest mortality rates. Here, we combine simulations and life‐history theory to explore how a doubling in mortality might result in population decline, mean life expectancy, and carbon carrying capacity of forests. Using a simulated forest, we also identify that the sampling strategy and effort required to detect a doubling in stem mortality is extensive. We recommend increased efforts at monitoring mortality and a better incorporation of life‐history theory, community composition, and application of changepoint detection statistics in mortality analyses.
Flash‐Calcined CuZnAl‐LDH as High‐Activity LT‐WGS Catalyst
Authors: Kowalik Paweł , Wiercioch Paweł , Bicki Robert , Próchniak Wiesław , Antoniak‐Jurak Katarzyna , Michalska Kamila , Słowik Grzegorz
Published: February 2019

The set of Cu/ZnO/Al2O3 catalysts was prepared by flash‐calcination of layered double hydroxycarbonate (CuZnAl‐LDH) precursor in a wide temperature range and conventional stationary technique. The catalytic materials were investigated by DTG/MS, XRD, N2O‐chemisorption, N2 sorption techniques and also SEM images has been collected. Low‐temperature water‐gas shift (LT‐WGS) activity evaluation was carried out on the basis of measurements made in a differential reactor in a kinetic regime. A relationship between calcinations mode and physicochemical parameters of the catalysts and their LT‐WGS activity has been estimated. The highest reaction rate has been determined for the catalyst prepared by flash‐calcination at mild conditions. It was shown that flash‐calcination of hydroxycarbonate precursors is efficient method for high‐activity LT‐WGS catalyst preparation due to limiting the risk of material overheating and sintering as it may occur using conventional calcinations technique.
Current Research Developments on the Processing and Improvement of the Nutritional Quality of Rapeseed (Brassica napus L.)
Authors: Beszterda Monika , Nogala‐Kałucka Małgorzata
Published: February 2019

Brassica napus is cultivated largely as a winter or semi‐winter form in Europe and Asia, respectively, whereas spring‐sown rape types are more adapted to the climatic conditions in Canada, northern Europe, and Australia. This plant, the third most important oil crop in the world after maize and oil palm, has had a unique history among those crops that have been targets of breeding and genetic modification. Although agronomy and genetic manipulations of B. napus plants to create seed with substantially no erucic acid content in the seed oil and meal largely free from aliphatic glucosinolates were major breakthroughs, opportunities for further advances in the reduction of antinutritive compounds/enhancement of bioactive compounds, in oil and meal health safety and quality, as well as in agronomic performance and pest resistance, are still greater today than they have ever been. Understanding and application of genetic control for key agronomic traits in B. napus, such as seed oil composition and concentration as well as their environmental interactions, are the main targets, which will underpin the development of the crop for cultivation in an extensive range of environments. It is also needed to improve phytochemical content through traditional breeding programs or through bioengineering of the phenylpropanoid pathway, leading to desirable secondary metabolite accumulation. This paper is a review of modifications (in the field of biotechnology, agronomy, and processing) that have been applied to improve the nutritional value of B. napus L.

Practical Applications: This paper has value for people starting their scientific work in the field related to the B. napus biotechnology and nutritional value of vegetable oils. In addition, it is a current compedium of knowledge for people working professionally in the oil industry. Moreover, this article is a cross‐section of the current achievements of genetic engineering in improving the composition of rapeseed and indicates key publications on this subject.

Brassica napus L., the third most important oil crop in the world after maize and oil palm, has a unique history among those crops that are targets of breeding and genetic modification. Effective tools of processing, biotechnology, and agronomy are essential to produce rapeseed oil with a high amount of bioactive compounds and continue to be employed in strengthening the product versatility.
Beyond Simple Substitution Patterns – Symmetrically Tetrasubstituted [2.2]Paracyclophanes as 3D Functional Materials
Authors: Weiland Kevin J. , Gallego Almudena , Mayor Marcel
Published: February 2019

[2.2]Paracyclophane is the prototypical layered hydrocarbon and has been essential for investigations of through‐space electronic interactions. Over the last years more examples of tetrasubstituted derivatives have been reported. This minireview discusses the synthetic approaches towards various substitution patterns and provides a survey over different approaches used to achieve and derivatize symmetric tetrasubstitution. The first two sections of this work present homo‐tetrasubstituted derivatives, while the third section gives insight into symmetrically hetero‐tetrasubstituted analogues. These approaches are briefly discussed, the resulting structures are presented in detail, and their specific properties resulting from the incorporation of [2.2]paracyclophane are elucidated.
Mechanistic Insights into the Reaction of N‐Propargylated Pyrrole‐ and Indole‐Carbaldehyde with Ammonia, Alkyl Amines, and Branched Amines: A Synthetic and Theoretical Investigation
Authors: Sari Ozlem , Seybek Ali Fatih , Kaya Serdal , Menges Nurettin , Erdem Safiye Sag , Balci Metin
Published: February 2019

The reaction of pyrrole‐ and indole‐carbaldehydes having a propargyl group attached to the nitrogen atom with various amines was studied. The reaction with ammonia formed pyrrolo[1,2‐a]pyrazine and pyrazino[1,2‐a]indole while the reaction with alkylamines such as methyl, ethyl, hexyl, and benzylamines formed the corresponding pyrazinone derivatives. Unexpectedly, the reaction with allylamine and propargylamine formed pyrazine derivatives in which the allyl and propargyl groups were removed from the molecule. On the other hand, the reaction of N‐propargylated pyrrole‐carbaldehyde formed indolizine derivatives upon reaction with sterically bulky adamantyl‐ and tert‐butylamines. To understand the main factors causing these differences in reactivity, the reaction mechanisms were studied by means of computational methods. Our calculations showed that bulky amines tend to attack the central carbon of allene formed by the isomerization of N‐propargyl functionality, while the attack on the carbonyl carbon by aliphatic amines is more profound.
Visible Light Enables Aerobic Iodine Catalyzed Glycosylation
Authors: Krumb Matthias , Lucas Tobias , Opatz Till
Published: February 2019

A versatile protocol for light induced catalytic activation of thioglycosides using iodine as an inexpensive and readily available photocatalyst was developed. Oxygen serves as a green and cost‐efficient terminal oxidant and irradiation is performed with a common household LED‐bulb. The scope of this glycosylation protocol was investigated in the synthesis of O‐glycosides with yields up to 95 %.
Characterization of wood‐laden flows in rivers
Authors: Ruiz‐Villanueva Virginia , Mazzorana Bruno , Bladé Ernest , Bürkli Livia , Iribarren‐Anacona Pablo , Mao Luca , Nakamura Futoshi , Ravazzolo Diego , Rickenmann Dieter , Sanz‐Ramos Marcos , Stoffel Markus , Wohl Ellen
Published: February 2019

Inorganic sediment is not the only solid‐fraction component of river flows; flows may also carry significant amounts of large organic material (i.e. large wood), but the characteristics of these wood‐laden flows (WLFs) are not well understood yet. With the aim to shed light on these relatively unexamined phenomena, we collected home videos showing natural flows with wood as the main solid component. Analyses of these videos as well as the watersheds and streams where the videos were recorded allowed us to define for the first time WLFs, describe the main characteristics of these flows and broaden the definition of wood transport regimes (adding a new regime called here hypercongested wood transport). According to our results, WLFs may occur repeatedly, in a large range of catchment sizes, generally in steep, highly confined single thread channels in mountain areas. WLFs are typically highly unsteady and the log motion is non‐uniform, as described for other inorganic sediment‐laden flows (e.g. debris flows). The conceptual integration of wood into our understanding of flow phenomena is illustrated by a novel classification defining the transition from clear water to hypercongested, wood and sediment‐laden flows, according to the composition of the mixture (sediment, wood, and water). We define the relevant metrics for the quantification and modelling of WLFs, including an exhaustive discussion of different modelling approaches (i.e. Voellmy, Bingham and Manning) and provide a first attempt to simulate WLFs. We draw attention to WLF phenomena to encourage further field, theoretical, and experimental investigations that may contribute to a better understanding of flows in river basins, leading to more accurate predictions, and better hazard mitigation and management strategies. © 2019 John Wiley & Sons, Ltd.
Teilhard de Chardin, human evolution and “Piltdown Man”
Authors: Thackeray J. Francis
Published: February 2019

Pierre Teilhard de Chardin was a French Jesuit paleontologist, priest, and philosopher. In the figures published in articles in 1943 and 1951, he attempted to draw a “plausible schematic reconstruction of the natural connections between fossil men” and a “phyletic composition of the human group”. I draw attention to Teilhard's reference to Eoanthropus (“Piltdown Man”) in small print in his figure that was first printed in 1943. Most suspiciously, there is no reference to this (supposedly important) genus in the associated text, nor is there any reference whatsoever to “Piltdown Man” in the article published in 1951. Even as early as January 1913, Teilhard may have been aware that “Piltdown Man” was a hoax or joke, artificially associating a human cranium with a modified orangutan mandible. A new suspect is Edgar Willett (rather than Charles Dawson). Teilhard may have been an advisory accomplice in a joke that went seriously wrong.
A morphometric study of the restinga ecotype of Anacardium occidentale (Anacardiaceae): wild coastal cashew populations from Piauí, Northeast Brazil
Authors: de Andrade Ivanilza Moreira , de Oliveira Nascimento Joana D'Arc , de Sousa Márcia Vieira , dos Santos Juelina Oliveira , Mayo Simon Joseph
Published: February 2019

The infraspecific taxonomy of wild Anacardium occidentale is little studied. We investigated whether wild populations on coastal dunes in Piauí, Brazil differed from non‐wild populations. Ten populations were sampled and twenty one morphological variables were measured. Variation within and between populations was investigated with univariate and multivariate statistics. Dune populations were mostly more similar to one another than to domesticated ones. There was significant correlation between inter‐population geographical distance and morphological dissimilarity. Classification methods showed 96.4% successful assignment to the dune category and 86% to 100% to dune populations individually, but dune and non‐dune populations overlap morphologically. Dune populations had shorter, broader leaves, shorter drupes and fewer secondary veins. Non‐dune coastal populations showed strongest similarity to dune populations. Populations distant from the coast were most divergent. The population from the cerrado region was most distinct, with thicker leaf blades and narrower petioles. The dune populations are recognised as the “restinga ecotype” of A. occidentale. Correlation of dissimilarity and distance may result from gene flow and/or non‐inherited environmental effects. Ecology and nomenclature (including the vernacular “cajuí”) of the restinga ecotype are reviewed. Further comparison of restinga populations is needed along the Brazilian coastline and with natural cerrado populations.
About the morphology and anatomy of pollen cones and the pollen presentation within the genus Fitzroya (Cupressaceae)
Authors: Dörken Veit Martin
Published: February 2019

Fitzroya pollen cones show several features that are common for callitroid Cupressaceae including an uniaxial structure, the arrangement of microsporangiophores in trimerous whorls, and hyposporangiate microsporangiophores with several abaxial microsporangia, and a terminal scutellum. The strictly downward position of the pollen cones throughout their entire ontogeny distinguishes Fitzroya clearly from all other Cupressaceae s.str., but is similar to some basal Cupressaceae s.l. and other coniferous groups, including several Pinaceae and Taxaceae. The peltate scutellum which covers the microsporangia is unique among Cupressaceae and all other conifers. It seems to play an important role in protecting maturing microsporangia, and also within the anemophily syndrome. In Fitzroya the pollen is not removed from the cone directly from its place of origin, but from secondary deposits located in distal parts of the scutellum. A comparable pollen exposure is lacking in all other Cupressaceae but is common in other conifers, for example several Pinaceae and Podocarpaceae. Thus, pollen cones of Fitzroya comprise features which are the common family traits of Cupressaceae, but also features that are unique among this family, but common in other conifers. In addition, also features were found that are unique among all conifers.
The foliar characters in Callitris (Callitroideae, Cupressaceae s. str.) and their evolutionary and ecological significance
Authors: Dörken V. M. , Ladd P. G. , Parsons R. F.
Published: February 2019

The foliar shift from juvenile needle leaves to the mature scale leaves was investigated in five Callitris species. Their habitats range from rainforest to the semi‐arid. In C. macleayana from the most mesic environment the change from needle to scale leaves is variable and juvenile leave are even retained on mature trees. In the other four species there is a rapid change in size and structure to scale leaves. Anatomically the photosynthetic tissue is condensed and stomatal area is limited compared to species with conventional leaves. A hypodermis is most prominent on the abaxial side of the leaves and may play a role in protection from high solar radiation as most species grow in high light areas. While stomata in the four taxa from wet or moderate rainfall areas are freely exposed, those of C. gracilis from semi‐arid habitats are well protected in longitudinal furrows between the decurrent leaves. The reduced leaf area of all species allows close association between the water‐conducting xylem and the stomata that will facilitate rapid leaf conductance. This links with the anisohydric physiology of the genus and the shallow rooting that can take advantage of brief rainfall events for species in arid climates.
Most gene fusions in cancer are stochastic events
Authors: Johansson Bertil , Mertens Fredrik , Schyman Tommy , Björk Jonas , Mandahl Nils , Mitelman Felix
Published: February 2019

Cancer‐associated gene fusions resulting in chimeric proteins or aberrant expression of one or both partner genes are pathogenetically and clinically important in several hematologic malignancies and solid tumors. Since the advent of different types of massively parallel sequencing (MPS), the number of identified gene fusions has increased dramatically, prompting the question whether they all have a biologic impact. By ascertaining the chromosomal locations of 8934 genes involved in 10 861 gene fusions reported in the literature, we here show that there is a highly significant association between gene content of chromosomes and chromosome bands and number of genes involved in fusions. This strongly suggests that a clear majority of gene fusions detected by MPS are stochastic events associated with the number of genes available to participate in fusions and that most reported gene fusions are passengers without any pathogenetic importance.
Glial fibrillary acidic protein expression alters astrocytic chemokine release and protects mice from cuprizone‐induced demyelination
Authors: Kramann Nadine , Menken Lena , Pförtner Ramona , Schmid Susanne N. , Stadelmann Christine , Wegner Christiane , Brück Wolfgang
Published: February 2019

Enhanced glial fibrillary acidic protein (GFAP) expression occurs in most diseases of the central nervous system. Thus far, little is known about the effect that GFAP exerts on astrocyte cell signaling. In the present study, we observed that silencing GFAP expression in isolated astrocytes leads to enhanced CCL2 and CXCL10 release, whereas overexpression of GFAP in astrocytes results in a significantly reduced CXCL10 release in vitro. Additionally, we analyzed transgenic mice carrying a full‐length copy of the wild‐type human GFAP gene. We demonstrate that a persistent GFAP increase alters the astrocytic cell signaling profile, thereby protecting oligodendrocytes, myelin and, subsequently, axons from cuprizone‐induced demyelination. Our study revealed that reduced CXCL10 mRNA was accompanied by reduced NF‐κB expression in astrocytes. Furthermore, analysis of human tissue from a patient with Alexander disease showed NF‐κB activation in astrocytes to be almost completely absent. Our findings indicate that regulation of GFAP expression in astrocytes is crucial for astrocyte signaling and function. Understanding the role of the cytoskeletal protein, GFAP is thus of importance as it is highly regulated in diseases of the central nervous system.
Welcoming the “Intel‐ethicist”
Authors: Banja John
Published: February 2019

In this issue of the Hastings Center Report, Mélanie Terrasse, Moti Gorin, and Dominic Sisti, urge ethicists to devote scholarly attention to a wave of troubling artificial intelligence applications affecting health consumers’ rights and the quality of their care. I very much agree. We already have neuroethicists, business ethicists, and genetics ethicists; AI‐related systems in health care present more than enough warrant to herald the appearance of a new ethics specialist—the “intel‐ethicist,” let’s say. Nonetheless, Terrasse and colleagues may have exaggerated some of the potential moral problems of AI. Examining only social media and e‐health programs, the authors produce an impressive array of questions to consider, but I will argue that two of them are not nearly as worrisome as might be supposed.
Longitudinally consistent estimates of intrinsic functional networks
Authors: Zhao Qingyu , Kwon Dongjin , Müller‐Oehring Eva M. , Le Berre Anne‐Pascale , Pfefferbaum Adolf , Sullivan Edith V. , Pohl Kilian M.
Published: February 2019

Increasing numbers of neuroimaging studies are acquiring data to examine changes in brain architecture by investigating intrinsic functional networks (IFN) from longitudinal resting‐state functional MRI (rs‐fMRI). At the subject level, these IFNs are determined by cross‐sectional procedures, which neglect intra‐subject dependencies and result in suboptimal estimates of the networks. Here, a novel longitudinal approach simultaneously extracts subject‐specific IFNs across multiple visits by explicitly modeling functional brain development as an essential context for seeking change. On data generated by an innovative simulation based on real rs‐fMRI, the method was more accurate in estimating subject‐specific IFNs than cross‐sectional approaches. Furthermore, only group‐analysis based on longitudinally consistent estimates identified significant developmental effects within IFNs of 246 adolescents from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. The findings were confirmed by the cross‐sectional estimates when the corresponding group analysis was confined to the developmental effects. Those effects also converged with current concepts of neurodevelopment.
Depth of invasion alone as an indication for postoperative radiotherapy in small oral squamous cell carcinomas: An International Collaborative Study
Authors: Ebrahimi Ardalan , Gil Ziv , Amit Moran , Yen Tzu‐Chen , Liao Chun‐ta , Chaturvedi Pankaj , Agarwal Jai Prakash , Kowalski Luiz P. , Köhler Hugo F. , Kreppel Matthias , Cernea Claudio R. , Brandao Jason , Bachar Gideon , Villaret Andrea Bolzoni , Fliss Dan M. , Fridman Eran , Robbins Kevin Thomas , Shah Jatin P. , Patel Snehal G. , Clark Jonathan R. ,   The International Consortium for Outcome Research (ICOR) in Head and Neck Cancer
Published: February 2019

Background

We aimed to investigate whether depth of invasion (DOI) should be an independent indication for postoperative radiotherapy (PORT) in small oral squamous cell carcinomas (SCC).

Methods

Retrospective analysis of DOI (<5, 5 to <10, ≥10 mm) and disease‐specific survival (DSS) in a multi‐institutional international cohort of 1409 patients with oral SCC ≤4 cm in size treated between 1990‐2011.

Results

In patients without other adverse factors (nodal metastases; close [<5 mm] or involved margins), there was no association between DOI and DSS, with an excellent prognosis irrespective of depth. In the absence of PORT, the 5‐year disease‐specific mortality was 10% with DOI ≥10 mm, 8% with DOI 5‐10 mm, and 6% with DOI <5 mm (P = .169), yielding an absolute risk difference of only 4%.

Conclusion

The deterioration in prognosis with increasing DOI largely reflects an association with other adverse features. In the absence of these, depth alone should not be an indication for PORT outside a clinical trial.
Validation of web‐based thyroid imaging reporting and data system in atypia or follicular lesion of undetermined significance thyroid nodules
Authors: Ha Su Min , Na Dong Gyu , Kim Ji‐Hoon , Kim Soo Chin , Baek Jung Hwan
Published: February 2019

Background

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) show variable malignancy risk. We validated the web‐based predictive models and the scoring system by the American College of Radiology (ACR) for AUS/FLUS nodules to stratify the malignancy risk.

Methods

From January 2011 to November 2014, 275 consecutive nodules diagnosed as AUS/FLUS were enrolled. The discrimination and calibration ability of a web‐based scoring with inclusion of biopsy result and sonographic features, old web‐based scoring model without biopsy result, and ACR models were assessed.

Results

The areas under the receiver operating characteristic curve of the validation set were 0.670 for the new web‐based model, 0.710 for the old web‐based model, and 0.732 for the ACR scoring risk‐stratification model. All models were well calibrated.

Conclusion

The web‐based scoring risk‐stratification model using the combined information of ultrasonography features and biopsy result for AUS/FLUS nodules to stratify malignancy risk presents an acceptable predictive accuracy.
Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis
Authors: Hara Koji , Takeda Atsuya , Tsurugai Yuichiro , Saigusa Yusuke , Sanuki Naoko , Eriguchi Takahisa , Maeda Shin , Tanaka Katsuaki , Numata Kazushi
Published: February 2019

Potentially curative treatments for early‐stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early‐stage HCC. Consecutive patients with ≤3 early‐stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3‐year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7‐9.2; versus 12.9%, 95% CI, 9.9‐16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3‐year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2‐77.7; and 70.4%; 95% CI, 58.5‐79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well‐compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.
Emergence of the Dedifferentiated Phenotype in Hepatocyte‐Derived Tumors in Mice: Roles of Oncogene‐Induced Epigenetic Alterations
Authors: Watanabe Kenji , Yamamoto Masahiro , Xin Bing , Ooshio Takako , Goto Masanori , Fujii Kiyonaga , Liu Yang , Okada Yoko , Furukawa Hiroyuki , Nishikawa Yuji
Published: February 2019

Hepatocellular carcinoma often reactivates the genes that are transiently expressed in fetal or neonatal livers. However, the mechanism of their activation has not been elucidated. To explore how oncogenic signaling pathways could be involved in the process, we examined the expression of fetal/neonatal genes in liver tumors induced by the introduction of myristoylated v‐akt murine thymoma viral oncogene (AKT), HRas proto‐oncogene, guanosine triphosphatase (HRASV12), and MYC proto‐oncogene, bHLH transcription factor (Myc), in various combinations, into mouse hepatocytes in vivo. Distinct sets of fetal/neonatal genes were activated in HRAS‐ and HRAS/Myc‐induced tumors: aldo‐keto reductase family 1, member C18 (Akr1c18), glypican 3 (Gpc3), carboxypeptidase E (Cpe), adenosine triphosphate‐binding cassette, subfamily D, member 2 (Abcd2), and trefoil factor 3 (Tff3) in the former; insulin‐like growth factor 2 messenger RNA binding protein 3 (Igf2bp3), alpha fetoprotein (Afp), Igf2, and H19, imprinted maternally expressed transcript (H19) in the latter. Interestingly, HRAS/Myc‐induced tumors comprised small cells with a high nuclear/cytoplasmic ratio and messenger RNA (mRNA) expression of delta‐like noncanonical Notch ligand 1 (Dlk1), Nanog homeobox (Nanog), and sex determining region Y‐box 2 (Sox2). Both HRAS‐ and HRAS/Myc‐induced tumors showed decreased DNA methylation levels of Line1 and Igf2 differentially methylated region 1 and increased nuclear accumulation of 5‐hydroxymethylcytosine, suggesting a state of global DNA hypomethylation. HRAS/Myc‐induced tumors were characterized by an increase in the mRNA expression of enzymes involved in DNA methylation (DNA methyltransferase [Dnmt1, Dnmt3]) and demethylation (ten‐eleven‐translocation methylcytosine dioxygenase 1 [Tet1]), sharing similarities with the fetal liver. Although mouse hepatocytes could be transformed by the introduction of HRAS/Myc in vitro, they did not express fetal/neonatal genes and sustained global DNA methylation, suggesting that the epigenetic alterations were influenced by the in vivo microenvironment. Immunohistochemical analyses demonstrated that human hepatocellular carcinoma cases with nuclear MYC expression were more frequently positive for AFP, IGF2, and DLK1 compared with MYC‐negative tumors. Conclusion: The HRAS signaling pathway and its interactions with the Myc pathway appear to reactivate fetal/neonatal gene expression in hepatocytic tumors partly through epigenetic alterations, which are dependent on the tumor microenvironment.
Evaluating the effectiveness of a website about masculinity and suicide to prompt help‐seeking
Authors: King Kylie , Schlichthorst Marisa , Turnure Jackie , Phelps Andrea , Spittal Matthew J. , Pirkis Jane
Published: February 2019

Issue addressed

A website was designed to form the core of a multimedia strategy surrounding the Man Up documentary – a three‐part documentary that aimed to address the problem of male suicide in Australia. Together these formed a media‐based, public health intervention that explored the link between masculinity and suicide and promoted help‐seeking. This is of great importance given the demonstrated link between masculine norms, men's reduced help‐seeking and suicidal thinking. This study assesses the website's effectiveness in facilitating help‐seeking and fostering conversations about suicide, mental health and help‐seeking. Help‐seeking indicators included website clicks to helping organisations, downloads of health information from the website and request for help received via emails.

Methods

Google Analytics data, emails to the Man Up team received through the website and open‐ended responses to an online survey were analysed.

Results

The website reached 43 140 users. Indictors of help‐seeking activity on the website included 307 outbound clicks to helping organisations and 802 downloads of health information. Qualitative analysis of emails received and responses to the survey demonstrated that Man Up's messages resonated with viewers and provided further evidence of help‐seeking.

Conclusion

The findings demonstrate that the website provided an important opportunity for people to engage with Man Up and seek help.

So what?

Media‐based public health interventions offer enormous potential to provide suicide prevention interventions and promote help‐seeking. The website evaluation findings provide insight into the ways in which websites can be used as part of a multimedia strategy to address the problem of male suicide.
Numerical estimation of pressure drop and heat transfer characteristics in annular‐finned channel heat exchangers with different channel configurations
Authors: Al Doori Wadhah H.
Published: February 2019

In this numerical investigation, three‐dimensional analysis has been used to study the effect of finned channels configuration of (circular, square, and triangular shape) and fin spacing with four rows in staggered arrangements. The finite volume method with k‐
ω turbulent model is applied to estimate the heat transfer and flow characteristics. The results illustrate that the development of the boundary layer between the fins surfaces is credited to the finned channels configuration, fin spacing, and Reynolds number. Moreover, the results of pressure drop and heat transfer with various channel configuration and different fin spacings (1.6, 2, and 4 mm) are presented and validated with the available correlations. The triangular‐finned channel with 1.6 mm fin spacing offered higher heat transfer enhancement followed by square‐ and circular‐finned channels. A considerable agreement was observed when the current findings and the existing correlations were compared, with a maximum deviation of 15% for all the cases.
Natural convective flow of a chemically reacting fluid in an annulus
Authors: Roy Nepal C. , Hossain Anwar , Gorla Rama S. R.
Published: February 2019

We examine the heat transfer and flow properties induced by natural convection in an annulus between a square enclosure and a circular cylinder filled with a chemically reacting fluid. During the exothermic reaction process in the reacting fluid, there generates heat that induces natural convection in the annulus. The problem is developed defining the vorticity‐stream function. We solve it with the use of the finite difference method. The results show that two counter‐rotating vortices generate in each half about the vertical symmetry line through the center of the inner cylinder. The lower eddies of the inner vortices get closer and closer with the decrease of the aspect ratio and the increase of the Rayleigh number, Frank‐Kamenetskii number, buoyancy force parameter, and Lewis number. Besides this, the eyes of the outer vortices expose similar characteristics for increasing values of the Rayleigh number and buoyancy force parameter, and for decreasing values of the aspect ratio and the Lewis number. It is remarkable that the flow field and the Nusselt number demonstrate completely distinct characteristics for the Lewis number unity, the aspect ratio equal to 0.1, and in the absence of the buoyancy force parameter.
Rogaratinib: A potent and selective pan‐FGFR inhibitor with broad antitumor activity in FGFR‐overexpressing preclinical cancer models
Authors: Grünewald Sylvia , Politz Oliver , Bender Sebastian , Héroult Mélanie , Lustig Klemens , Thuss Uwe , Kneip Christoph , Kopitz Charlotte , Zopf Dieter , Collin Marie‐Pierre , Boemer Ulf , Ince Stuart , Ellinghaus Peter , Mumberg Dominik , Hess‐Stumpp Holger , Ziegelbauer Karl
Published: February 2019

Aberrant activation in fibroblast growth factor signaling has been implicated in the development of various cancers, including squamous cell lung cancer, squamous cell head and neck carcinoma, colorectal and bladder cancer. Thus, fibroblast growth factor receptors (FGFRs) present promising targets for novel cancer therapeutics. Here, we evaluated the activity of a novel pan‐FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models. In vitro kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3 and 4. In line with this, rogaratinib reduced proliferation in FGFR‐addicted cancer cell lines of various cancer types including lung, breast, colon and bladder cancer. FGFR and ERK phosphorylation interruption by rogaratinib treatment in several FGFR‐amplified cell lines suggests that the anti‐proliferative effects are mediated by FGFR/ERK pathway inhibition. Furthermore, rogaratinib exhibited strong in vivo efficacy in several cell line‐ and patient‐derived xenograft models characterized by FGFR overexpression. The observed efficacy of rogaratinib strongly correlated with FGFR mRNA expression levels. These promising results warrant further development of rogaratinib and clinical trials are currently ongoing (ClinicalTrials.gov Identifiers: NCT01976741, NCT03410693, NCT03473756).
Inhibition of HSP90 overcomes resistance to chemotherapy and radiotherapy in pancreatic cancer
Authors: Nagaraju Ganji Purnachandra , Zakka Katerina M. , Landry Jerome C. , Shaib Walid L. , Lesinski Gregory B. , El‐Rayes Bassel F.
Published: February 2019

Resistance of pancreatic ductal adenocarcinoma (PDAC) to radiotherapy and chemotherapy represents a significant clinical issue. Although the mechanisms of resistance are multi‐faceted, client proteins of heat shock protein 90 (HSP90) such as hypoxia induced factor‐1α (HIF‐1α) have a central role in this process. The purpose of this investigation was to evaluate inhibition of HSP90 as a therapeutic strategy for radiosensitization in pancreatic cancer. Ganetespib, a selective inhibitor of HSP90, was evaluated as a radio‐sensitizer in setting of PDAC. Inhibition of HSP90 by ganetespib potentiated the ability of radiation therapy to limit cell proliferation and colony formation in vitro. HIF‐1α expression was upregulated by irradiation and HIF‐1α‐overexpressing stable cell lines were resistant to radiation. Inhibition of HSP90 with ganetespib reversed the effects of HIF‐1α overexpression, by reducing signaling via proliferative, angiogenic and anti‐apoptotic pathways. The potentiation of the antitumor effects of chemoradiotherapy by ganetespib and modulation of key pathways (e.g. HIF‐1α, STAT3, and AKT) was confirmed in vivo in nude mice bearing HPAC xenograft tumors. These novel data highlight HIF‐1α‐mediated mechanisms of HSP90 inhibition that sensitize PDAC cells to chemoradiotherapy. This pathway and its pleiotropic effects warrant further evaluation in concert with conventional therapy in pancreatic cancer clinical trials.
Cachexia‐related long noncoding RNA, CAAlnc1, suppresses adipogenesis by blocking the binding of HuR to adipogenic transcription factor mRNAs
Authors: Shen Lei , Han Jun , Wang Haiyu , Meng Qingyang , Chen Linlin , Liu Yuguo , Feng Ying , Wu Guohao
Published: February 2019

Cancer‐associated cachexia (CAC) is a devastating syndrome characterized by progressive losses of adipose tissue and skeletal muscle. CAC‐related adipose tissue loss (CAL) occurs early and is associated with a shorter survival time. To explore potential regulatory long noncoding RNAs (lncRNAs) of CAL, RNA microarrays were used to analyze the transcriptomes of white adipose tissue from CAC mice vs. control mice. A set of differentially expressed lncRNAs was identified, and among them was CAAlnc1, which suppressed adipogenesis of C3H10 cells as demonstrated by gain‐of‐function and loss‐of‐function experiments. RNA immunoprecipitation and pull‐down assays revealed Hu antigen R (HuR) was an important binding partner of CAAlnc1. The interaction between CAAlnc1 and HuR blocked the binding of HuR to adipogenic transcription factor mRNAs and further downregulated the expression of these transcription factors. This study generated a list of CAL‐related lncRNAs and provided details of a functional lncRNA which may play an important role in CAL.
Advancing Theoretical Frameworks for Intersectional Research on Women in STEM
Authors: Gaston Gayles Joy , Smith Katie N.
Published: February 2019

Research on women in STEM often silences the voices of minoritized populations, such as women of color, in
part because the most commonly used theoretical frameworks do not center or contextualize their experiences. This chapter highlights the importance of critical perspectives and methodologies such as intersectionality in research design. We conclude with implications for using critical approaches to disrupt the status quo and advance minoritized populations in STEM.
Institutional Practices and Policies for Recruiting and Supporting Undergraduate Women in Engineering Across Four‐Year Institutions
Authors: Trautvetter Lois Calian
Published: February 2019

How do undergraduate student experiences and STEM gender gaps differ across diverse postsecondary sectors and programmatic contexts? The research presented uses mixed methods to examine how institutional cultures, practices, and policies play roles in both recruiting and retaining undergraduate women in engineering. Practical examples are provided. Furthermore, challenges for supporting faculty/staff who provide outreach and advice to students regarding academic and professional careers as well as future research directions are discussed.
Biochemical properties and oxalate‐degrading activity of oxalate decarboxylase from bacillus subtilis at neutral pH
Authors: Conter Carolina , Oppici Elisa , Dindo Mirco , Rossi Luigia , Magnani Mauro , Cellini Barbara
Published: February 2019

Oxalate decarboxylase (OxDC) from Bacillus subtilis is a Mn‐dependent hexameric enzyme that converts oxalate to carbon dioxide and formate. OxDC has greatly attracted the interest of the scientific community, mainly due to its biotechnological and medical applications in particular for the treatment of hyperoxaluria, a group of pathologic conditions caused by oxalate accumulation. The enzyme has an acidic optimum pH, but most of its applications involve processes occurring at neutral pH. Nevertheless, a detailed biochemical characterization of the enzyme at neutral pH is lacking. Here, we compared the structural–functional properties at acidic and neutral pH of wild‐type OxDC and of a mutant form, called OxDC‐DSSN, bearing four amino acid substitutions in the lid (Ser161‐to‐Asp, Glu162‐to‐Ser, Asn163‐toSer, and Ser164‐to‐Asn) that improve the oxalate oxidase activity and almost abolish the decarboxylase activity. We found that both enzymatic forms do not undergo major structural changes as a function of pH, although OxDC‐DSSN displays an increased tendency to aggregation, which is counteracted by the presence of an active‐site ligand. Notably, OxDC and OxDC‐DSSN at pH 7.2 retain 7 and 15% activity, respectively, which is sufficient to degrade oxalate in a cellular model of primary hyperoxaluria type I, a rare inherited disease caused by excessive endogenous oxalate production. The significance of the data in the light of the possible use of OxDC as biological drug is discussed. © 2019 IUBMB Life, 1–11, 2019
Sustaining Multilingual Literacies: Looking Through an Immigrant Lens to Inform Practice
Authors: Camela Vianey
Published: February 2019

This department explores how teachers can sustain students’ multilingual literacies and reimagine literacy learning across multiple contexts in conversation with researchers, practitioners, and communities.