bluuebunny/crossref_metadata_2025 huggingface dataset:
A contemporary analysis of racial disparities in recommended and received treatment for head and neck cancer
Authors: Nocon Cheryl C. , Ajmani Gaurav S. , Bhayani Mihir K.
Published: October 2019

Background

Racial disparities in squamous cell carcinoma of the head and neck (HNSCC) negatively affect non‐Hispanic black (NHB) patients. This study was aimed at understanding how treatment is prescribed and received across all HNSCC subsites.

Methods

With the National Cancer Database, patients from 2004 to 2014 with surgically resectable HNSCCs, including tumors of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (LX), were studied. The treatment received was either upfront surgery or nonsurgical treatment. Treatment patterns were compared according to race and subsite, and how these differences changed over time was evaluated.

Results

NHB patients were less likely than non‐Hispanic white (NHW) patients to receive surgery across all subsites (relative risk [RR] for OC, 0.87; RR for OP, 0.75; RR for HP, 0.73; RR for LX, 0.87; all P values <.05). They were also more likely to refuse a recommended surgery (RR for OC, 1.50; RR for OP, 1.23; RR for HP, 1.23; RR for LX, 1.34), and this difference was significant except for HP. NHB patients were more likely to not be offered surgery across all subsites (RR for OC, 1.38; RR for OP, 1.07; RR for HP, 1.05; RR for LX, 1.03; all P values <.05). Rates of surgery increased and rates of not being offered surgery declined for both NHB and NHW patients from 2004 to 2014, but the absolute disparities persisted in 2014.

Conclusions

Across all HNSCC subsites, NHB patients were less likely than NHW patients to be recommended for and receive surgery and were more likely to refuse surgery. These differences have closed over time but persist. Enhanced shared decision making may improve these disparities.
Changes in internet use and wishes of cancer survivors: A comparison between 2005 and 2017
Authors: van Eenbergen Mies C. H. J. , Vromans Ruben D. , Boll Dorry , Kil Paul J. M. , Vos Caroline M. , Krahmer Emiel J. , Mols Floortje , van de Poll‐Franse Lonneke V.
Published: October 2019

Background

Given the major changes in internet use for health communication, the objective of the current study was to compare the internet use and wishes of cancer survivors between 2005 and 2017.

Methods

The authors drew a sample of 390 patients in 2005 and 539 patients in 2017 who were diagnosed with breast (128 patients in 2005 and 143 patients in 2017), prostate (96 patients in 2005 and 126 patients in 2017), or gynecologic (89 patients in 2005 and 188 patients in 2017) cancer or lymphoma (77 patients in 2005 and 82 patients in 2017) in 4 different hospitals for the periods 2002 through 2004 and 2014 through 2016. These patients were sent a paper‐based questionnaire that contained 45 questions regarding demographics and 4 functions of internet use: content, communication, community, and e‐health.

Results

The response in 2017 (53%) was lower than that in 2005 (75%). Survivors browsed the internet most frequently to search for information regarding cancer shortly after being diagnosed and while waiting for treatment. There was little change noted with regard to the relative importance attached to the various subjects. In 2017, significant increases were evident with regard to finances (+33%), health care insurance (+29%), and genetics and/or heritability (+27%). The wishes expressed in 2005 by patients were realized in part in 2017.

Conclusions

A significant sample of cancer survivors in the Netherlands have indicated that the internet is an important source of information regarding their illness. However, little change was evident over the past 15 years with regard to patients' priorities regarding their wishes for internet use. The wishes of users in 2005 were found to accurately reflect the internet use of the majority of patients in 2017. The results of the current study support the belief that health care professionals should expand their online services and tailor them toward the needs and wishes of their patients.
Patterns of recurrence and metastasis in BRCA1/BRCA2‐associated breast cancers
Authors: Song Yun , Barry William T. , Seah Davinia S. , Tung Nadine M. , Garber Judy E. , Lin Nancy U.
Published: October 2019

Background

Breast cancer subtypes are associated with distinct metastatic patterns. Whether germline BRCA1/BRCA2 mutation status is independently associated with central nervous system (CNS) relapse, controlling for tumor subtype, is unknown.

Methods

Patients who were treated at Dana‐Farber Cancer Institute and diagnosed with a first locoregional recurrence (LRR) or metastasis between 1981 and 2014 were identified using 2 institutional registries: 1) patients treated for recurrent breast cancer and 2) patients who underwent BRCA testing. The frequencies of LRR, sites of metastasis, and breast cancer‐specific survival from LRR or metastasis were calculated, and the factors associated with CNS recurrence were evaluated using multivariable logistic regression models.

Results

The final study cohort included 30 BRCA1 mutation carriers, 32 BRCA2 mutation carriers, and 270 noncarriers. Most BRCA1 carriers (73%) had triple‐negative breast cancer; whereas most BRCA2 carriers (72%) had hormone receptor‐positive tumors. BRCA1 carriers frequently experienced lung and distant lymph node metastasis, whereas BRCA2 carriers and noncarriers most often experienced bone metastasis. Although CNS disease occurred frequently in both BRCA1 and BRCA2 carriers (53% BRCA1, 50% BRCA2, 25% noncarriers; P < .001), only BRCA2 mutation (P = .006) was significantly associated with CNS metastasis in multivariable analysis controlling for tumor subtype. BRCA2 mutation (P = .01), triple‐negative subtype (P < .001), and the involvement of CNS (P < .001) and other non‐CNS distant sites (relative to locoregional recurrence or contralateral disease; P < .001) at presentation of recurrent breast cancer were associated with risk for mortality.

Conclusions

CNS involvement is frequent in women with germline BRCA1/BRCA2 mutations who have metastatic breast cancer. BRCA2 mutation carriers had a significantly higher frequency of CNS metastasis than noncarriers when controlling for breast cancer subtype.
Pancreatoblastoma: Cytologic and histologic analysis of 12 adult cases reveals helpful criteria in their diagnosis and distinction from common mimics
Authors: Reid Michelle D. , Bhattarai Shristi , Graham Rondell P. , Pehlivanoglu Burcin , Sigel Carlie S. , Shi Jiaqi , Saqi Anjali , Shirazi Maryam , Xue Yue , Basturk Olca , Adsay Volkan
Published: October 2019

Background

Pancreatoblastoma (PBL) is a rare malignant pancreatic tumor seen predominantly in childhood, and its cytologic diagnosis remains challenging.

Methods

Twelve fine‐needle‐aspirations from 11 adults were analyzed.

Results

In total, 6 men and 5 women (median age, 45 years; age range, 32‐60 years) had tumors measuring a median 5.6 cm (range, 2.5‐12 cm) located in the pancreatic head (n = 7) or tail (n = 4), including 3 with familial adenomatous polyposis (FAP)/FAP‐related syndromes and 4 with metastasis at diagnosis. The median follow‐up was 39.8 months (range, 0.8‐348 months), and 5 patients died of disease. The original cytology diagnoses were: PBL (n = 2), neuroendocrine neoplasm (n = 2), poorly differentiated neuroendocrine carcinoma (n = 2), well differentiated neuroendocrine tumor (n = 1), poorly differentiated carcinoma (n = 2), “positive for malignancy” (n = 1), acinar cell carcinoma (n = 1), and epithelioid neoplasm with endocrine and acinar differentiation versus PBL (n = 1). Universal cytopathologic findings included hypercellularity; 3‐dimensional clusters; and single, monotonous, blast‐like cells that were from 1.5 to 2.0 times the size of red blood cells with high nuclear‐to‐cytoplasmic ratio, fine chromatin, small, distinct nucleoli, and a resemblance to well differentiated neuroendocrine tumor and poorly differentiated neuroendocrine carcinoma. Branching pseudopapillae (n = 7) and grooved nuclei (n = 3) raised the differential diagnosis of solid‐pseudopapillary neoplasm, but with more atypia. Uncommon features included pleomorphism (n = 4) and numerous mitoses (n = 1). Squamoid morules were seen on smears (n = 5) or cell blocks (n = 6) in 70% of patients and were characterized by epithelioid cells with elongated, streaming nuclei, fine chromatin, absent nucleoli, and positive nuclear β‐catenin (n = 6 of 8). The median Ki‐67 index was 21% (range, 2%‐70%), and neuroendocrine marker expression was common (100%), but acinar markers were variable (63%).

Conclusions

A combination of cytologic findings in PBL, including a predominant population of primitive blast‐like cells, subtle squamoid morules, frequent neuroendocrine and variable acinar phenotype, should facilitate accurate cytologic diagnosis and distinction from common mimics.
Precise color capture using custom color targets
Authors: Olejnik‐Krugly Agnieszka , Korytkowski Przemyslaw
Published: October 2019

We have developed a procedure to achieve a high accuracy of color capture for digital still cameras for cultural heritage digitization. The procedure uses a standard color target and additional spectral measurements directly on the artwork. A set of complementary colors is determined thanks to an initial analysis of the digital image and a comparison with the standard color target. The developed procedure results in a digital copy that better represents the colors of the original than using only standard color targets.
Autonomic nervous system functioning in early childhood: Responses to cognitive and negatively valenced emotional challenges
Authors: Zeytinoglu Selin , Calkins Susan D. , Leerkes Esther M.
Published: October 2019

Although autonomic nervous system (ANS) functioning is “context‐dependent,” few studies examined children's normative sympathetic and parasympathetic autonomic responses to distinct challenges in early childhood years. Examining children's ANS responsivity to distinct challenges is important for understanding normative autonomic responses toward everyday life stressors and identifying paradigms that effectively elicit a “stress response.” We examined children's (N = 278) sympathetic (preejection period [PEP]) and parasympathetic (respiratory sinus arrhythmia [RSA]) responses to cognitive (i.e., problem‐solving and cognitive control) and negatively valenced emotional (i.e., blocked goal and unfairness) challenges in preschool, kindergarten, and grade 1. Children, on average, demonstrated parasympathetic inhibition (RSA withdrawal) in response to all challenges but the magnitude of these responses depended on the task. Children showed sympathetic activation (PEP shortening) toward the problem‐solving task at each assessment and there was no sample‐level change in the magnitude of this response over time. Children showed greater sympathetic responsivity toward the cognitive control task over time, with evidence for a sympathetic activation response only in grade 1. Children experienced sympathetic inhibition (PEP lengthening) toward the unfairness tasks but did not experience significant sympathetic responsivity toward the blocked goal tasks. Parasympathetic responsivity to most challenges were modestly stable but there was no stability in sympathetic responsivity across time.
Extramacrochaetae promotes branch and bouton number via the sequestration of daughterless in the cytoplasm of neurons
Authors: Waddell Edward A. , Viveiros Jennifer M. , Robinson Erin L. , Sharoni Michal A. , Latcheva Nina K. , Marenda Daniel R.
Published: October 2019

The Class I basic helix–loop–helix (bHLH) proteins are highly conserved transcription factors that are ubiquitously expressed. A wealth of literature on Class I bHLH proteins has shown that these proteins must homodimerize or heterodimerize with tissue‐specific HLH proteins in order to bind DNA at E‐box consensus sequences to control tissue‐specific transcription. Due to its ubiquitous expression, Class I bHLH proteins are also extensively regulated posttranslationally, mostly through dimerization. Previously, we reported that in addition to its role in promoting neurogenesis, the Class I bHLH protein daughterless also functions in mature neurons to restrict axon branching and synapse number. Here, we show that part of the molecular logic that specifies how daughterless functions in neurogenesis is also conserved in neurons. We show that the Type V HLH protein extramacrochaetae (Emc) binds to and represses daughterless function by sequestering daughterless to the cytoplasm. This work provides initial insights into the mechanisms underlying the function of daughterless and Emc in neurons while providing a novel understanding of how Emc functions to restrict daughterless activity within the cell.
Exploring patterns of beta‐diversity to test the consistency of biogeographical boundaries: A case study across forest plant communities of Italy
Authors: Chiarucci Alessandro , Nascimbene Juri , Campetella Giandiego , Chelli Stefano , Dainese Matteo , Giorgini Daniele , Landi Sara , Lelli Chiara , Canullo Roberto
Published: October 2019

Aim

To date, despite their great potential biogeographical regionalization models have been mostly developed on descriptive and empirical bases. This paper aims at applying the beta‐diversity framework on a statistically representative data set to analytically test the consistency of the biogeographical regionalization of Italian forests.

Location

Italy.

Taxon

Vascular plants.

Methods

Forest plant communities were surveyed in 804 plots made in a statistically representative sample of forest communities made by 201 sites of Italian forests across the three biogeographical regions of the country: Alpine, Continental, and Mediterranean. We conducted an ordination analysis and an analysis of beta‐diversity, decomposing it into its turnover and nestedness components.

Results

Our results provide only partial support to the consistency of the biogeographical regionalization of Italy. While the differences in forest plant communities support the distinction between the Alpine and the other two regions, differences between Continental and Mediterranean regions had lower statistical support. Pairwise beta‐diversity and its turnover component are higher between‐ than within‐biogeographical regions. This suggests that different regional species pools contribute to assembly of local communities and that spatial distance between‐regions has a stronger effect than that within‐regions.

Main conclusions

Our findings confirm a biogeographical structure of the species pools that is captured by the biogeographical regionalization. However, nonsignificant differences between the Mediterranean and Continental biogeographical regions suggest that this biogeographical regionalization is not consistent for forest plant communities. Our results demonstrate that an analytical evaluation of species composition differences among regions using beta‐diversity analysis is a promising approach for testing the consistency of biogeographical regionalization models. This approach is recommended to provide support to the biogeographical regionalization used in some environmental conservation polices adopted by EU.
Species‐specific habitat preferences do not shape the structure of a crested newt hybrid zone (Triturus cristatus x T. carnifex)
Authors: Mačát Zdeněk , Rulík Martin , Jablonski Daniel , Reiter Antonín , Jeřábková Lenka , Rada Stanislav , Mikulíček Peter
Published: October 2019

Reproductive isolation barriers maintain the integrity of species by preventing interspecific gene flow. They involve temporal, habitat or behavioral isolation acting before fertilization, and postzygotic isolation manifested as hybrid mortality or sterility. One of the approaches of how to study reproductive isolation barriers is through the analysis of hybrid zones. In this paper, we describe the structure of a hybrid zone between two crested newt species (Triturus cristatusandT. carnifex) in the southern part of the Czech Republic using morphological, microsatellite, and mitochondrial (mtDNA) markers. Specifically, we tested the hypothesis that the structure of the hybrid zone is maintained by species‐specific habitat preferences. Comparing the genetic structure of populations with geographical and ecological parameters, we found that the hybrid zone was structured primarily geographically, withT. cristatus‐like populations occurring in the northeast andT. carnifex‐like populations in the southwest. DespiteT. cristatustending to occur in deeper ponds andT. carnifexon localities with more shading, the effect of both ecological parameters on the structure of the zone was minimal. Next, we corroborated thatT. carnifexindividuals and some hybrids possess mtDNA ofT. dobrogicus, whose nuclear background was not detected in the studied hybrid zone. Hybridization betweenT. carnifexandT. dobrogicus(resulting in unidirectional mtDNA introgression) had to predate subsequent formation of the hybrid zone betweenT. cristatusandT. carnifex. Populations of crested newts in the southern part of the Czech Republic thus represent a genetic mosaic of nuclear and mitochondrial genomes of three species.
Joint estimation of survival and breeding probability in female dolphins and calves with uncertainty in state assignment
Authors: Couet Pauline , Gally François , Canonne Coline , Besnard Aurélien
Published: October 2019

While the population growth rate in long‐lived species is highly sensitive to adult survival, reproduction can also significantly drive population dynamics. Reproductive parameters can be challenging to estimate as breeders and nonbreeders may vary in resighting probability and reproductive status may be difficult to assess. We extended capture–recapture (CR) models previously fitted for data on other long‐lived marine mammals to estimate demographic parameters while accounting for detection heterogeneity between individuals and state uncertainty regarding reproductive status. We applied this model to data on 106 adult female bottlenose dolphins observed over 13 years. The detection probability differed depending on breeding status. Concerning state uncertainty, offspring were not always sighted with their mother, and older calves were easier to detect than young‐of‐the‐year (YOY), respectively, 0.79 (95% CI 0.59–0.90) and 0.58 (95% CI 0.46–0.68). This possibly led to inaccurate reproductive status assignment of females. Adult female survival probability was high (0.97 CI 95% 0.96–0.98) and did not differ according to breeding status. Young‐of‐the‐year and 1‐year‐old calves had a significantly higher survival rate than 2‐year‐old (respectively, 0.66 CI 95% 0.50–0.78 and 0.45 CI 95% 0.29–0.61). This reduced survival is probably related to weaning, a period during which young are exposed to more risks since they lose protection and feeding from the mother. The probability of having a new YOY was high for breeding females that had raised a calf to the age of 3 or lost a 2‐year‐old calf (0.71, CI 95% 0.45–0.88). Yet, this probability was much lower for nonbreeding females and breeding females that had lost a YOY or a 1‐year‐old calf (0.33, 95% CI 0.26–0.42). The multievent CR framework we used is highly flexible and could be easily modified for other study questions or taxa (marine or terrestrial) aimed at modeling reproductive parameters.
Adaptive landscape genetics and malaria across divergent island bird populations
Authors: Armstrong Claire , Davies Richard G. , González‐Quevedo Catalina , Dunne Molly , Spurgin Lewis G. , Richardson David S.
Published: October 2019

Environmental conditions play a major role in shaping the spatial distributions of pathogens, which in turn can drive local adaptation and divergence in host genetic diversity. Haemosporidians, such as Plasmodium (malaria), are a strong selective force, impacting survival and fitness of hosts, with geographic distributions largely determined by habitat suitability for their insect vectors. Here, we have tested whether patterns of fine‐scale local adaptation to malaria are replicated across discrete, ecologically differing island populations of Berthelot's pipits Anthus berthelotii. We sequenced TLR4, an innate immunity gene that is potentially under positive selection in Berthelot's pipits, and two SNPs previously identified as being associated with malaria infection in a genome‐wide association study (GWAS) in Berthelot's pipits in the Canary Islands. We determined the environmental predictors of malaria infection, using these to estimate variation in malaria risk on Porto Santo, and found some congruence with previously identified environmental risk factors on Tenerife. We also found a negative association between malaria infection and a TLR4 variant in Tenerife. In contrast, one of the GWAS SNPs showed an association with malaria risk in Porto Santo, but in the opposite direction to that found in the Canary Islands GWAS. Together, these findings suggest that disease‐driven local adaptation may be an important factor in shaping variation among island populations.
Experimental migration upward in elevation is associated with strong selection on life history traits
Authors: DeMarche Megan L. , Angert Amy L. , Kay Kathleen M.
Published: October 2019

One of the strongest biological impacts of climate change has been the movement of species poleward and upward in elevation. Yet, what is not clear is the extent to which the spatial distribution of locally adapted lineages and ecologically important traits may also shift with continued climate change. Here, we take advantage of a transplant experiment mimicking up‐slope seed dispersal for a suite of ecologically diverse populations of yellow monkeyflower (Mimulus guttatus sensu lato) into a high‐elevation common garden during an extreme drought period in the Sierra Nevada mountains, California, USA. We use a demographic approach to quantify fitness and test for selection on life history traits in local versus lower‐elevation populations and in normal versus drought years to test the potential for up‐slope migration and phenotypic selection to alter the distribution of key life history traits in montane environments. We find that lower‐elevation populations tend to outperform local populations, confirming the potential for up‐slope migration. Although selection generally favored some local montane traits, including larger flowers and larger stem size at flowering, drought conditions tended to select for earlier flowering typical of lower‐elevation genotypes. Taken together, this suggests that monkeyflower lineages moving upward in elevation could experience selection for novel trait combinations, particularly under warmer and drier conditions that are predicted to occur with continued climate change.
Feeding increases the number of offspring but decreases parental investment of Red Sea coral Stylophora pistillata
Authors: Bellworthy Jessica , Spangenberg Jorge E. , Fine Maoz
Published: October 2019

Successful reproductive output and recruitment is crucial to coral persistence and recovery following anthropogenic stress. Feeding is known to alter coral physiology and increase resilience to bleaching.

The goal of the study was to address the knowledge gap of the influence of feeding on reproductive output and offspring phenotype.

Colonies of Stylophora pistillata from the Northern Gulf of Aqaba (Red Sea) were fed an Artemia diet or unfed for 5 months during gametogenesis, fertilization, and brooding. In addition, time to settlement and mortality of planulae were assessed at water temperatures ranging from winter temperature (22°C) to three degrees above average peak summer temperature (31°C). A range of physiological parameters was measured in parents and offspring.

In brooding parents, feeding significantly increased protein concentration and more than tripled the number of released planulae. Planulae from unfed colonies had higher chlorophyll per symbiont concentration and concomitantly higher photosynthetic efficiency compared to planulae from fed parents. In settlement assays, planulae showed a similar thermal resistance as known for this Red Sea adult population. Mortality was greater in planulae from unfed parents at ambient and 3°C above ambient temperature despite higher per offspring investment in terms of total fatty acid content. Fatty acid profiles and relative abundances were generally conserved between different fed and unfed colonies but planulae were enriched in monounsaturated fatty acids relative to adults, that is, 16:1, 18:1, 20:1, 22:1, and 24:1 isomers.

Ultimately the availability of zooplankton could influence population physiology and recruitment in corals.
C‐type lectin receptors of the Dectin‐1 cluster: Physiological roles and involvement in disease
Authors: Tone Kazuya , Stappers Mark H.T. , Willment Janet A. , Brown Gordon D.
Published: October 2019

C‐type lectin receptors (CLRs) are essential for multicellular existence, having diverse functions ranging from embryonic development to immune function. One subgroup of CLRs is the Dectin‐1 cluster, comprising of seven receptors including MICL, CLEC‐2, CLEC‐12B, CLEC‐9A, MelLec, Dectin‐1, and LOX‐1. Reflecting the larger CLR family, the Dectin‐1 cluster of receptors has a broad range of ligands and functions, but importantly, is involved in numerous pathophysiological processes that regulate health and disease. Indeed, these receptors have been implicated in development, infection, regulation of inflammation, allergy, transplantation tolerance, cancer, cardiovascular disease, arthritis, and other autoimmune diseases. In this mini‐review, we discuss the latest advancements in elucidating the function(s) of each of the Dectin‐1 cluster CLRs, focussing on their physiological roles and involvement in disease.
Opposing peripheral fates of tissue‐restricted self antigen‐specific conventional and regulatory CD4+ T cells
Authors: Zhang Zimeng , Legoux Francois P. , Vaughan Spencer W. , Moon James J.
Published: October 2019

The development of self antigen‐specific T cells is influenced by how the self antigen is expressed. Here, we created a mouse in which a model self antigen is conditionally expressed in different tissue environments. Using peptide:MHCII tetramer‐based cell enrichment methods, we examined the development of corresponding endogenous self antigen‐specific CD4+ T cell populations. While ubiquitous self antigen expression resulted in efficient deletion of self antigen‐specific T cells in the thymus, some tissue‐restricted expression patterns resulted in partial deletion of the population in peripheral lymphoid organs. Deletion specifically affected Foxp3− conventional T cells (Tconv) with a bias towards high avidity TCR expressing cells in the case of thymic, but not peripheral deletion. In contrast, Foxp3+ Treg exhibited elevated frequencies with increased TCR avidity. T cells surviving deletion were functionally impaired, with Tconv cells exhibiting more impairment than Tregs. Collectively, our results illustrate how postthymic recognition of tissue‐restricted self antigens results in opposing developmental fates for Tconv and Treg cell subsets.
Formulation and Characterization of Taxifolin‐Loaded Lipid Nanovesicles (Liposomes, Niosomes, and Transfersomes) for Beverage Fortification
Authors: Hasibi Forough , Nasirpour Ali , Varshosaz Jaleh , García‐Manrique Pablo , Blanco‐López Maria Carmen , Gutiérrez Gemma , Matos María
Published: October 2019

In this study, nanovesicles such as transfersomes, niosomes, and liposomes prepared by an ethanol injection method (EIM) (EIM) and formulated with soybean lecithin, Tween 80, Span 60, and cholesterol, are used to improve the bioavailability of taxifolin, a natural antioxidant with beneficial properties for health and food preservation. Morphology, stability, and the in‐vitro release of the optimal formulations are fully examined. The obtained results indicate that taxifolin‐loaded nanovesicles present sizes ranging between 98 and 215 nm along with a narrow size distribution (polydispersity index less than 0.250). The zeta potential of nanovesicles is negative and in the range of −20.40 to −32.20 mV. The optimal formulations with the maximum encapsulation efficiency (72–75%) are the transfersomes formulated with lecithin and Tween 80 in the presence and absence of cholesterol. Additionally, in vitro release behavior of nanovesicles shows low taxifolin released (3.68–10.13%) at intestinal conditions, whereas more than 90% of taxifolin is released in gastrointestinal conditions. The compatibility between taxifolin and nanovesicles components is confirmed by FTIR. Transmission electron microscopy demonstrates spherical shaped particles around 200 nm. Backscattering profiles variations show the potential application of taxifolin nanovesicles for producing fortified apple juice with excellent physical stability.

Practical Applications: Taxifolin is a flavanonol, which fulfills a particular task in preserving stable functions of the circulatory system owing to its special antioxidant ability and biological activity. Nevertheless, its low bioavailability is a salient drawback for biomedical and food applications. Thus, the current study is conducted to encapsulate taxifolin in nanovesicles (such as liposome, niosome, transfersome) by EIM to improve its bioavailability. Nanocarriers with relatively decent physical stability and high encapsulation efficiency can be brought about through Tween 80, soybean lecithin, and in the presence and absence of cholesterol as stabilizer which ensures the successful delivery of taxifolin to food formats such as beverages.
Enzyme‐mediated assembly of chimeric membrane proteins at phospholipid bilayers
Authors: Scott D. , Tullman J. , Kelman Z. , Marino J. , Silin V.
Published: October 2019

Integral membrane proteins (IMPs) pose a challenge to study in vitro, as it is difficult to reproduce the membrane‐imbedded context of their native state. In this study, we developed a generalized strategy for the assembly of chimeric IMPs within a phospholipid bilayer surface based on a two‐step process that first imbeds the insoluble domain of the IMP into a phospholipid layer and then ligates the soluble part of the IMP to the imbedded portion under mild biochemical conditions using a mutant sortase A enzyme. The approach is demonstrated using the transmembrane domain of epidermal growth factor receptor (EGFR) and the soluble extracellular loop of the B‐lymphocyte antigen CD20 protein in a POPC tethered bilayer membrane (tBLM). The conditions of the enzymatic reaction were optimized for peptide ligation at the tBLM surface and the role of Ca2+ ions in ligation efficiency examined. Additionally, binding of the CD20/EGFR chimera in the context of a membrane environment by the rituximab antibody was measured to assess functionality.
A 2D explicit numerical scheme–based pore pressure cohesive zone model for simulating hydraulic fracture propagation in naturally fractured formation
Authors: Li Yang , Liu Wei , Deng Jingen , Yang Yingxin , Zhu Haiyan
Published: October 2019

In this work, a 2D pore pressure cohesive zone model is presented to simulate the hydraulic fracture propagation in naturally fractured formation, in which the fracturing process is governed by a bilinear cohesive zone model equipped with Coulomb's friction law and the fluid flow within the hydraulic fracture is described by the lubrication equation. In this model, fluid leak‐off into rock matrix is ignored and a fully explicit temporal integration scheme is adopted to overcome the convergence issue of conventional implicit scheme (eg, Newton‐Raphson method). The advantage of the proposed model is that it does not require any special crossing criterion to determine the interaction behavior when the hydraulic fracture hits the natural fracture. Implementation of the model was described in detail, and then, the model was verified with well‐known analytical solution of KGD problem and criteria of hydraulic fracture crossing natural fracture. The capability of the proposed model to capture the interaction behavior between hydraulic fracture and natural fracture was demonstrated by the good agreement of the modeling result and analytical solution. Several numerical cases were performed to investigate the impact of key factors on fracture network evolution during hydraulic fracturing treatment. Results show that fracture network is not only governed by the spatial distribution of natural fracture, but also greatly affected by the initial hydraulic aperture of natural fracture and in situ stress contrast.
A study of the dynamic movement rule of overlying strata combinations using a short‐wall continuous mining and full‐caving method
Authors: Wen Jinhao , Cheng Weimin , Chen Lianjun , Shi Shaoshuai , Wen Zhijie
Published: October 2019

At present in China, short‐wall working face coal‐mining methods are among the main methods used for the high‐efficiency recoveries of boundary coal pillars and residual pillars. In traditional short‐wall mining methods, overlying roofs are supported by coal pillars. However, issues such as the excessive number of coal pillars, low coal recovery efficiency, large areas of hanging roof arches, etc, have been encountered. In view of the aforementioned issues of the current short‐wall mining technology, this study took the short‐wall mining of the Yujialiang Mine in the Shendong mining area as the project background. The study then proposed a judgment method for the key stratum on the working face of the mine using a short‐wall continuous mining and full‐caving method. The proposed method was based on the theory of elastic plates and was verified using the theoretical analysis results of similar material simulation experiments. FLAC 3D software was adopted to analyze the stress and displacement evolution processes of the overlying rock strata during the advancement of the working face using a short‐wall continuous mining and full‐caving method. The results showed that the short‐wall continuous mining and full‐caving method not only had the ability to improve the recovery rate, but was also able to realize the effective control of the roof areas, thereby avoiding any large areas of hanging arches. The short‐wall continuous mining and full‐caving method is potentially of important significance for the improvement of coal recovery rates, as well as for the safe and highly efficient mining of boundary coal pillars and residual pillars in mines under special conditions.
Effects of swirling flow on ultralight particle dispersion characteristics in coaxial jet combustor
Authors: Liu Yang , Zhang Li , Zhou Lixing
Published: October 2019

The dispersion characteristics of ultralight particle (expanded graphite) in swirling mixture particle‐laden coaxial jet combustor was modeled and numerically predicted using developed second‐order moment gas‐particle multifluid turbulent model. An improved gas‐particle and particle‐particle Reynolds stress transport to describe its anisotropic behaviors was proposed. Experimental validation for single‐phase particle flow has been conducted with satisfied agreement. The multifluid hydrodynamic parameters, that is, number density, particle velocity, fluctuation velocity, Reynolds stress correlation of gas‐particle and particle‐particles, and effects of swirling number are investigated. The results found that the ultralight particles exhibited the distinctive anisotropic behaviors, and their unique flow structures were quite different from those of heavier particles. Under the strong swirling flow condition, the anisotropic dispersions were enhanced and concentration at recirculation regions increased. The axial velocities and fluctuations, and the axial‐axial and tangential‐tangential stress correlations of gas‐particles were weakened. The effect of swirling strength on ultralight particle dispersions is more sensitive in comparison with heavier particle.
Diet, feeding behavior, and jaw architecture of Taï monkeys: Congruence and chaos in the realm of functional morphology
Authors: McGraw W. Scott , Daegling David J.
Published: October 2019

We review feeding and mandibular anatomy in a community of West African monkeys. We use field observations, food material property data, and skeletal specimens from the Ivory Coast's Taï Forest to explore the factors that shape mandibular architecture in colobines and cercopithecines. Despite excellent geographic control across our sample, the fit between bone form (as conventionally described) and functional activity (as we perceive it) is not spectacular. We present a thought experiment to assess how well we could reconstruct diet in the Taï monkeys if we only had skeletons and teeth to study. This exercise indicated that we would be correct about half the time. Our analyses reinforce the notion that diet is anything but a monolithic variable and that better success at relating mandibular form to food must incorporate information on ingestive and processing behavior, geometric and material properties of foods, and both material and structural data on jaws themselves.
Systemic risk in market microstructure of crude oil and gasoline futures prices: A Hawkes flocking model approach
Authors: Jang Hyun Jin , Lee Kiseop , Lee Kyungsub
Published: October 2019

We propose the Hawkes flocking model that assesses systemic risk in high‐frequency processes at the two perspectives—endogeneity and interactivity. We examine the futures markets of West Texas Intermediate (WTI) crude oil and gasoline for the past decade, and perform a comparative analysis with conditional value‐at‐risk as a benchmark measure. In terms of high‐frequency structure, we derive the empirical findings. The endogenous systemic risk in WTI was significantly higher than that in gasoline, and the level at which gasoline affects WTI was constantly higher than that in the opposite case. Moreover, although the relative influence's degree was asymmetric, its difference has gradually reduced.
Of Slide Rules and Stethoscopes: AI and the Future of Doctoring
Authors: Truog Robert D.
Published: October 2019

Historically, the practice of medicine has been a physically intimate endeavor. Physicians have used their hands to palpate and reveal the secrets hidden within the body. Smelling the breath for the ketosis of diabetes or tasting the skin for the saltiness of cystic fibrosis were among the physician's essential practices. Today, perhaps the most defining characteristic of a brilliant clinician is the ability to synthesize many images—from electrocardiograms, ultrasounds, CT scans, and so forth—into a coherent picture that can guide our diagnosis and treatment. Yet this is rapidly becoming a Sisyphean task. Just as we are about to drown in a deluge of data, AI is throwing us a life preserver, to save not only our patients but ourselves. But where will AI take us?
California Takes the Lead on Data Privacy Law
Authors: Rothstein Mark A. , Tovino Stacey A.
Published: October 2019

In the early 1970s, Congress considered enacting comprehensive privacy legislation, but it was unable to do so. In 1974, it passed the Privacy Act, applicable only to information in the possession of the federal government. In the intervening years, other information privacy laws enacted by Congress, such as the Health Insurance Portability and Accountability Act, have been weak and sector specific. With the explosion of information technology and the growing concerns about an absence of effective federal privacy laws, the legal focus has shifted to the states. Signaling a new direction in state data privacy and consumer protection law, the California Consumer Privacy Act establishes important rights and protections for California residents with regard to the collection, use, disclosure, and sale of their personal information. The CCPA is certain to spur similar legislation and to affect national and international businesses that collect data from California's residents. Understanding the new law is important for all data‐driven industries, including health care.
Human‐Animal Chimeras, “Human” Cognitive Capacities, and Moral Status
Authors: Degrazia David
Published: October 2019

In “Human‐Animal Chimeras: The Moral Insignificance of Uniquely Human Capacities,” Julian Koplin explores a promising way of thinking about moral status. Without attempting to develop a model in any detail, Koplin picks up Joshua Shepherd's interesting proposal that we think about moral status in terms of the value of different kinds of conscious experience. For example, a being with the most basic sort of consciousness and sentience would have interests that matter morally, while a being whose consciousness featured the riches of loving affection, say, might have greater moral status and therefore deserve some sort of priority if the interests of the two beings conflicted. This approach represents an improvement over the more common, transparently anthropocentric habits of thinking about moral status, whether in connection with evaluating human‐animal chimera research, deciding what one can ethically eat, or pursuing some other moral inquiry.
Loss of Xanthine Oxidoreductase Potentiates Propagation of Hepatocellular Carcinoma Stem Cells
Authors: Sun Qikai , Zhang Zechuan , Lu Yijun , Liu Qiaoyu , Xu Xiaoliang , Xu Jianbo , Liu Yang , Yu Hailong , Yu Decai , Sun Beicheng
Published: October 2019

Background and Aims

Liver cancer stem cells (CSCs) exist in the tumor environment and are critically involved in the initiation and progression of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of self‐renewal and maintenance of liver CSCs remain poorly understood.

Approach and Results

We identified that xanthine oxidoreductase (XOR), which was expressed at low levels in human HCC samples and liver CSCs, restrained HCC formation and chemoresistance by attenuating liver CSC propagation. Mechanistically, XOR physically interacts with ubiquitin‐specific peptidase 15 (USP15), thereby promoting deubiquitination of Kelch‐like ECH associated protein 1 (KEAP1) to stabilize its expression, which leads to degradation of Nrf2 (nuclear factor erythroid 2–related factor 2) through ubiquitination and subsequently reactive oxygen species accumulation in liver CSCs. Finally, our data reveal that XOR promotes USP15‐mediated Nrf2‐KEAP1 signaling to block liver CSCs and tumor propagation.

Conclusion

We identified that XOR may represent a potential therapeutic target for clinical intervention in HCC driven by liver CSCs.
Do Additional Clinical Risk Factors Improve the Performance of Fracture Risk Assessment Tool (FRAX) Among Postmenopausal Women? Findings From the Women's Health Initiative Observational Study and Clinical Trials
Authors: Crandall Carolyn J , Larson Joseph , Cauley Jane A , Schousboe John T , LaCroix Andrea Z , Robbins John A , Watts Nelson B , Ensrud Kristine E
Published: October 2019

The ability of the fracture risk assessment tool (FRAX) to discriminate between women who do and do not experience major osteoporotic fractures (MOFs) is suboptimal. Adding common clinical risk factors may improve discrimination. We used data from the Women's Health Initiative, a prospective study of women aged 50 to 79 years at baseline (n = 99,413; n = 5722 in BMD subset) enrolled at 40 US clinical centers. The primary outcome was incident MOFs assessed annually during 10 years' follow‐up. For prediction of incident MOF, we examined the area under the receiver operatic characteristic curve (AUC) and net reclassification index (NRI) of the FRAX model alone and FRAX plus additional risk factors (singly or together: type 2 diabetes mellitus, frequent falls [≥2 falls in the past year], vasomotor symptoms, self‐reported physical function score [RAND 36‐item Health Survey subscale), and lumbar spine BMD). For NRI calculations, high risk was defined as predicted MOF risk ≥20%. We also assessed calibration as observed MOF events/expected MOF events. The AUC value for FRAX without BMD information was 0.65 (95% CI, 0.65 to 0.66). Compared with the FRAX model (without BMD), the AUC value was not improved by the addition of vasomotor symptoms, diabetes, or frequent falls, but was minimally increased by adding physical function score (AUC 0.66, 95% CI, 0.66 to 0.67). FRAX was well‐calibrated for MOF prediction. The NRI of FRAX + additional variables versus FRAX alone was 5.7% (p < 0.001) among MOF cases and −1.7% among noncases (p > 0.99). Additional variables (diabetes, frequent falls, vasomotor symptoms, physical function score, or lumbar spine BMD) did not yield meaningful improvements in NRI or discrimination of FRAX for MOFs. Future studies should assess whether tools other than FRAX provide superior discrimination for prediction of MOFs. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Synthesis of novel bis‐sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase
Authors: Biçer Abdullah , Kaya Rüya , Anıl Barış , Turgut Cin Günseli , Gülcin İlhami , Gültekin Mehmet Serdar
Published: October 2019

In this study, a series of novel bis‐sulfone compounds (2a‐2j) were synthesized by oxidation of the bis‐sulfides under mild reaction conditions. The bis‐sulfone derivatives were characterized by 1H‐NMR, 13C‐NMR, Fourier‐transform infrared spectroscopy, and elemental analysis techniques. Nuclear Overhauser effect experiments were performed to determine the orientation of the sulfonyl groups in bis‐sulfone derivatives. Here, we report the synthesis and testing of novel bis‐sulfone compound–based hybrid scaffold of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the development of novel molecules toward the therapy of Alzheimer's disease. The novel synthesized bis‐sulfone compounds demonstrated Ki values between 11.4 ± 3.4 and 70.7 ± 23.2 nM on human carbonic anhydrase I isozyme (hCA I), 28.7 ± 6.6 to 77.6 ± 5.6 nM on human carbonic anhydrase II isozyme (hCA II), 18.7 ± 2.61 to 95.4 ± 25.52 nM on AChE, and 9.5 ± 2.1 to 95.5 ± 1.2 nM on BChE enzymes. The results showed that novel bis‐sulfone derivatives can have promising drug potential for glaucoma, leukemia, epilepsy, and Alzheimer's disease, which are associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes.
lncRNA RMRP knockdown suppress hepatocellular carcinoma biological activities via regulation miRNA‐206/TACR1
Authors: Hongfeng Zhao , Andong Ju , Liwen Sun , Mingping Bi , Xiaowei Yang , Mingyong Li , Aimin Yue
Published: October 2019

Long noncoding RNA, RNA component of mitochondrial RNA processing endoribonuclease (RMRP) plays an important role in cancer development and is closely correlated with prognosis in cancer patients. However, whether RMRP affects prognosis in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to investigate the expression level of RMRP in HCC and its correlation with prognosis in patients with HCC and explain the effects and associated mechanisms by conducting an in vitro study. The high expression level of RMRP was correlated with poor prognosis in patients with HCC. Using in vitro analysis, RMRP knockdown suppressed HCC cell proliferation, invasion, and migration (P < .05). miRNA‐206 overexpression had similar effects in HCC cell lines (Bel‐7402 and Huh‐7). Using Western blot analysis and cellular immunofluorescence detection, RMRP downregulation significantly suppressed TACR1/Erk1/2 pathway, while miRNA‐206 was significantly upregulated (P < .05). RMRP downregulation inhibits HCC‐related biological activities by the regulation of miRNA‐206/TACR1.