bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 2 trial of abiraterone acetate without glucocorticoids for men with metastatic castration‐resistant prostate cancer
Authors: McKay Rana R. , Werner Lillian , Jacobus Susanna J. , Jones Alexandra , Mostaghel Elahe A. , Marck Brett T. , Choudhury Atish D. , Pomerantz Mark M. , Sweeney Christopher J. , Slovin Susan F. , Morris Michael J. , Kantoff Philip W. , Taplin Mary‐Ellen
Published: November 2018

Background

Abiraterone acetate suppresses adrenal androgens and glucocorticoids through the inhibition of CYP17; however, given the risk of mineralocorticoid excess, it is administered with glucocorticoids. Herein, the authors performed a phase 2, single‐arm study that was designed to assess the safety of abiraterone acetate without steroids in patients with castration‐resistant prostate cancer.

Methods

Eligible patients had castration‐resistant prostate cancer with controlled blood pressure and normal potassium. Patients initially received abiraterone acetate at a dose of 1000 mg daily alone. Those with persistent or severe mineralocorticoid toxicity received treatment with prednisone initiated at a dose of 5 mg twice daily. Therapy was continued until radiographic progression, toxicity, or withdrawal. The primary objective of the current study was to determine the percentage of men requiring prednisone to manage mineralocorticoid toxicity. Toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0.

Results

A total of 58 patients received at least 1 dose of abiraterone acetate; the majority had metastases (53 patients; 91.4%). Sixteen patients (27.6%) received prior chemotherapy, 6 patients (10.3%) received prior enzalutamide, and 4 patients (7%) received prior ketoconazole. Grade 3 to 4 adverse events of interest included hypertension (9 patients; 15.5%) and hypokalemia (4 patients; 7%). There was no grade ≥3 edema. Seven patients (12%) initiated prednisone therapy for mineralocorticoid toxicity, 3 patients for hypertension (5%), and 4 patients for hypokalemia (7%). Two patients initiated prednisone therapy for fatigue (3%). Forty patients (68%) experienced a decline in prostate‐specific antigen of ≥50% with the use of abiraterone acetate alone. Patients with lower baseline levels of androstenedione (P = .04), androsterone (P = .01), dehydroepiandrosterone (P = .03), and 17‐hydroxyprogesterone (P = .03) were found to be more likely to develop mineralocorticoid toxicity.

Conclusions

Treatment with abiraterone acetate without steroids is feasible, although clinically significant adverse events can occur in a minority of patients. The use of abiraterone acetate without prednisone should be balanced with the potential for toxicity and requires close monitoring.
ONOFIC‐based leakage reduction technique for FinFET domino circuits
Authors: Magraiya Vijay Kumar , Gupta Tarun Kumar
Published: November 2018

A new technique ON/OFf logIC (ONOFIC) is proposed in this paper for designing domino logic circuits in fin‐field effect transistor (FinFET) deep submicron technology. In this technique, a block named ONOFIC is inserted between pull‐up network (PUN) and pull‐down network (PDN) of domino circuits. The proposed technique is simulated in FinFET short gate (SG) and low power (LP) mode. The subthreshold current which plays a major role to determinate leakage power is very low in this technique. Two‐, 4‐, 8‐, and 16‐input OR gates are simulated with 32‐nm node FinFET technology. In FinFET LP mode, the subthreshold leakage power of the proposed technique is reduced by 15% to 24.3% at 25°C and reduced by 8.71% to 23.4% at 110°C compared with standard domino circuits. The subthreshold leakage power of the proposed circuit is reduced by 19.2% to 57.3% at 25°C and reduced by 17.6% to 60.7% at 110°C compared with leakage control transistor (LECTOR)‐based circuits. In FinFET SG mode, the subthreshold leakage power of the proposed technique is reduced by 7.69% to 17.7% at 25°C and reduced by 0 to 7.85% at 110°C compared with standard domino circuits. The subthreshold leakage power of the proposed circuit is reduced by 60.4% to 73.9% at 25°C and reduced by 45.1% to 65.5% at 110°C compared with LECTOR‐based circuits. The proposed technique is also efficient to reduce subthreshold leakage power in deep nanometer technology nodes from 7 to 20 nm.
Estimates of gene flow and dispersal in wild riverine Brook Trout (Salvelinus fontinalis) populations reveal ongoing migration and introgression from stocked fish
Authors: Bruce Spencer A. , Wright Jeremy J.
Published: November 2018

As anthropogenic impacts accelerate changes to landscapes across the globe, understanding how genetic population structure is influenced by habitat features and dispersal is key to preserving evolutionary potential at the species level. Furthermore, knowledge of these interactions is essential to identifying potential constraints on local adaptation and for the development of effective management strategies. We examined these issues in Brook Trout (Salvelinus fontinalis) populations residing in the Upper Hudson River watershed of New York State by investigating the spatial genetic structure of over 350 fish collected from 14 different sampling locations encompassing three river systems. Population genetic analyses of microsatellite data suggest that fish in the area exhibit varying degrees of introgression from nearby State‐directed supplementation activities. Levels of introgression in these populations correlate with water‐way distance to stocking sites, although genetic population structure at the level of individual tributaries as well as their larger, parent river systems is also detectable and is dictated by migration and influenced by habitat connectivity. These findings represent a significant contribution to the current literature surrounding Brook Trout migration and dispersal, especially as it relates to larger interconnected systems. This work also suggests that stocking activities may have far‐reaching consequences that are not directly limited to the immediate area where stocking occurs. The framework and data presented here may aid in the development of other local aquatic species‐focused conservation plans that incorporate molecular tools to answer complex questions regarding diversity mapping, and genetically important conservation units.
Early returning long‐distance migrant males do pay a survival cost
Authors: Lerche‐Jørgensen Mathilde , Korner‐Nievergelt Fränzi , Tøttrup Anders P. , Willemoes Mikkel , Thorup Kasper
Published: November 2018

Timing of return to the breeding area presumably optimizes breeding output in migrants. How timing affects the other components of fitness — survival, has been comparatively little studied. Returning too early in spring is expected to be associated with high mortality in insectivorous migrants when weather conditions are still unsuitable. Yet, males in particular arrive early to get access to the best territories which have been suggested to cause arrival before it is optimal for their survival. For the outward migration in autumn, timing is presumably less directly associated with reproduction and fitness and how it might affect survival is not well understood. We use data of eight songbird species ringed across Denmark to investigate how timing of return migration in spring and departure migration in autumn close to the breeding areas affects survival for short‐ and long‐distance migrants. Further, we compare survival optimum to the timing of males and females at a stopover site in Denmark in three sexually dimorphic, protandric species. We find a clear relationship between return migration and survival which differs between short‐ and long‐distance migrants: Survival decreases with date for short‐distance migrants and a bell‐shaped relationship, with low survival for earliest and latest individuals, for long‐distance migrants. In protandric species, the majority of males return before survival is optimal, whereas females on average return close to the survival optimum. The pattern of survival in relation to autumn timing is less clear, although a similar bell‐shaped relationship is suggested for long‐distance migrants. Our findings support the predicted mortality consequences of too early return to the breeding grounds and also that selection for early return in males leads to suboptimal migration timing regarding survival.
Cumulative reproductive costs on current reproduction in a wild polytocous mammal
Authors: Kroeger Svenja B. , Blumstein Daniel T. , Armitage Kenneth B. , Reid Jane M. , Martin Julien G. A.
Published: November 2018

The cumulative cost of reproduction hypothesis predicts that reproductive costs accumulate over an individual's reproductive life span. While short‐term costs have been extensively explored, the prevalence of cumulative long‐term costs and the circumstances under which such costs occur alongside or instead of short‐term costs, are far from clear. Indeed, few studies have simultaneously tested for both short‐term and cumulative long‐term reproductive costs in natural populations. Even in mammals, comparatively little is known about cumulative effects of previous reproduction, especially in species with high variation in offspring numbers, where costs could vary among successful reproductive events. Here, we quantify effects of previous short‐term and cumulative long‐term reproduction on current reproduction probability and litter size in wild female yellow‐bellied marmots (Marmota flaviventer) and test how these effects vary with age and between two contrasting environments. We provide evidence for cumulative long‐term effects: females that had both reproduced frequently and weaned large litters on average in previous years had decreased current reproduction probability. We found no evidence for short‐term reproductive costs between reproductive bouts. However, females weaned larger litters when they had weaned larger litters on average in previous years and had lower current reproduction probability when their previous reproductive success was low. Together these results suggest that, alongside persistent among‐individual variation, long‐term reproductive history affects current reproductive success.
Vegetation trends over eleven years on mountain summits in NW Argentina
Authors: Carilla Julieta , Halloy Stephan , Cuello Soledad , Grau Alfredo , Malizia Agustina , Cuesta Francisco
Published: November 2018

As global climate change leads to warmer and dryer conditions in the central Andes, alpine plant communities are forced to upward displacements following their climatic niche. Species range shifts are predicted to have major impacts on alpine communities by reshuffling species composition and abundances. Using a standardized protocol, we surveyed alpine plant communities in permanent plots on four high Andean summits in NW Argentina, which range from 4,040 to 4,740 m a.s.l. After a baseline survey in 2006–2008, we resurvey the same plots in 2012, and again in 2017. We found a significant decrease in plant cover, species richness, and diversity across the elevation gradient in the three censuses and a strong decrease in soil temperature along the elevation gradient. We found a high plant community turnover (37%–49%) among censuses, differentiating according to summits and aspects; major changes of community turnover were observed in the lowest summit (49%) and on the northern (47%) and western (46%) aspects. Temporal patterns in community changes were represented by increases in plant cover in the highest summit, in species richness in the lower summit, and in diversity (Shannon index) in the four summits, over time, together with increase in small herbs and non‐tussock grasses. We suggest that the observed trend in plant community dynamics responds to short‐term temperature and precipitation variability, which is influenced by El Niño Southern Oscillation (ENSO), and due to time lags in plant community response, it may take much longer than one decade for the observed trends to become stables and statistically significant. Our study provides an important foundation for documenting more profound changes in these subtropical alpine plant communities as global climate change continues.
Synthesis of 3,3‐Dichloropiperidines and Further Functionalization via Pd‐Catalyzed Cross‐Coupling Reactions of the Dichloromethylene Moiety
Authors: Van Beek Wim E. , Smets Robert J. , Kushwaha Khushbu , Herrebout Wouter A. , Abbaspour Tehrani Kourosch
Published: November 2018

A new synthetic methodology for the functionalization of the dichloromethylene moiety in 3,3‐dichloropiperidines via Pd‐catalyzed cross‐coupling reactions is reported. A range of 3,3‐dichloropiperidines was synthesized via a hydride induced cyclization of α,α,δ‐trichloroaldimines or an indium(III) triflate catalyzed alkynylation/cyclization procedure of α,α,δ‐trichloroaldimines. Subsequently, a dehydrochlorination followed by a cross‐coupling with the thus formed vinylic chloride was envisioned. The non‐alkynylated 3,3‐dichloropiperidines could be regioselectively eliminated and by careful choice of solvent and base both of the two regioisomeric vinyl chlorides could be exclusively formed. Palladium‐catalyzed Suzuki cross‐coupling of the thus formed 5‐chloro‐1,2,3,6‐tetrahydropyridines led to C3‐substituted 1,2,3,6‐tetrahydropyridines, which could be easily reduced to 3‐substituted piperidines, generating therapeutic agent (±)‐Preclamol for example. The 2‐alkynyl‐3,3‐dichloropiperidines were regioselectively eliminated giving the cyclic enamine, which was subsequently cross‐coupled in one‐pot. The presence of the alkynyl function, in this case, clearly directs elimination towards enamine structures. Hydrogenation of the resulting, unstable 2‐alkynyl‐3‐substituted‐1,2,3,4‐tetrahydropyridines, yields stable 2,3‐disubstituted piperidines.
Documenting archaeological thin sections in high‐resolution: A comparison of methods and discussion of applications
Authors: Haaland Magnus M. , Czechowski Matthias , Carpentier Frank , Lejay Mathieu , Vandermeulen Bruno
Published: November 2018

Optical thin section observations represent the core empirical basis for most micromorphological interpretations at archaeological sites. These observations, which often vary in size and shape, are usually documented through digital graphic representations such as photomicrographs, scans, or figures. Due to variability in documentation practices, however, visual thin section data can be captured with a range of methods and in many different formats and resolutions. In this paper, we compare and evaluate five common image‐based methods for documenting thin sections in high‐resolution: a flatbed scanner, a film scanner, a macro photography rig, and conventional stereo and light microscopes. Through the comparison results, we demonstrate that advances in digital imaging technology now allow for fast and high‐resolution visual recording of entire thin sections up to at least ×30 magnification. We suggest that adopting a digital micromorphological documentation practice has several advantages. First, a digital thin section may be observed more efficiently and consistently, for example, on a computer screen, and the spatial configuration of large or complex features may be more accurately documented. Second, they allow for the establishment of digital repositories that may promote scientific reproducibility and inter‐laboratory communication, as well as lay the foundations for more consensus‐based educational training of archaeological micromorphology.
The acceleration of CAR‐T therapy in non‐Hodgkin lymphoma
Authors: Munshi Pashna N. , Ujjani Chaitra
Published: November 2018

Recent advances in diffuse large B‐cell lymphomas have included both identification of high‐risk subtypes characterized by multiply relapsed and/or refractory disease as well as novel treatment in the form of cellular therapy. Chimeric antigen receptor (CAR)‐T cell therapy is a recently developed approach to address the poor outcomes in this patient population. The CAR‐T cell construct has evolved although several iterations as it transitioned from the lab to the clinic. Three major studies have evaluated the efficacy of CD19‐directed CAR‐T cell therapy in aggressive B‐cell non‐Hodgkin lymphoma; each demonstrating durable complete remissions in heavily pretreated patients. The cost of this remarkable therapy, however, includes cytokine release syndrome and neurotoxicity shortly after administration as well as delayed infectious complications due to B‐cell aplasia. Future investigations are focused on the optimizing both safety and efficacy of CAR‐T cell therapy.
Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort
Authors: Fang Ai‐Ping , Chen Pei‐Yan , Wang Xiao‐Yan , Liu Zhao‐Yan , Zhang Dao‐Ming , Luo Yun , Liao Gong‐Cheng , Long Jing‐An , Zhong Rong‐Huan , Zhou Zhong‐Guo , Xu Yan‐Jun , Xu Xiao‐Jun , Ling Wen‐Hua , Chen Min‐Shan , Zhang Yao‐Jun , Zhu Hui‐Lian
Published: November 2018

Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer‐specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22–2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36–3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89–1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99–2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.
Chemerin/ChemR23 axis triggers an inflammatory response in keratinocytes through ROS‐sirt1‐NF‐κB signaling
Authors: Wang Yuan , Huo Jia , Zhang Dingwei , Hu Gang , Zhang Yanfei
Published: November 2018

Psoriasis is a chronic disease which carries the emotional and social burden, promotes joint disability and raises comorbidity possibility in patients. Obesity is closely correlated with the occurrence of psoriasis and adipokines produced by adipose tissues were found to be critical culprits. Chemerin is one of them and its expression was increased in patients with psoriatic arthritis. In our hypothesis, chemerin might act on keratinocytes and promote an inflammatory response, which plays an essential role in psoriatic epidermis. To validate our hypothesis, HaCaT cells and primary human keratinocytes were treated with chemerin (5, 10, and 20 ng/mL for 24 hours). Enzyme‐linked immunosorbent assay (ELISA) was used to determine the secretion of inflammatory factors. Nuclear factor‐κB (NF‐κB) activation and p65 acetylation were evaluated by Western blot analysis. The expression and activity of sirtuin 1 (sirt1), a deacetylase act on p65, were also analyzed. The results showed that chemerin prompted inflammatory factors secretion, NF‐κB activation and p65 acetylation through chemerin receptor 23 receptor. Chemerin constrained the expression and deacetylase activity of sirt1 through augment of reactive oxygen species (ROS) production. Additionally, chemerin exacerbated psoriasiform dermatitis in imiquimod‐treated mice model. In conclusion, chemerin can seduce inflammatory response and promote NF‐κB activation through inhibition of sirt1 activity by ROS production.
microRNA‐383 regulates cell viability and apoptosis by mediating Wnt/β‐catenin signaling pathway in non–small cell lung cancer
Authors: Gu Biao , Wang Jipeng , Song Yaqi , Wang Qi , Wu Qingquan
Published: November 2018

The aim of this study was to investigate the roles of microRNA‐383 (miRNA‐383) in progression of non–small cell lung cancer (NSCLC) and the potential mechanism. The expressions of miR‐383 and Wnt1 protein were detected in lung cancer tissues and cells by quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot analysis. After the transfection of miR‐383 mimics, si‐Wnt1 or miR‐383+Wnt1, the viability and apoptosis of NSCLC cells were detected by cell counting kit‐8 and terminal deoxynucleotidyl transferase–mediated dUTP nick‐end labeling, respectively. The interaction between miR‐383 and Wnt1 was investigated by luciferase activity and Western blot analysis. Cells stably transfected with miR‐383 mimics were inoculated into the right axillary of nude mice by subcutaneous injection. The tumor volume and weight were measured, and the expressions of miR‐383, Wnt1, β‐catenin, and cyclin D1 were detected by qRT‐PCR and Western blot analysis. The expression of miR‐383 was significantly decreased, and the level of Wnt1 was significantly increased (P < 0.05) in lung cancer tissues and cells. Upregulation of miR‐383 or inhibition of Wnt1 expression inhibited the cell viability and induce apoptosis in NSCLC cells. Moreover, Wnt1 was the target gene of miR‐383, and its overexpression weakened the regulatory effect of miR‐383 on cell viability and apoptosis in NSCLC cells. Besides, the addition of miR‐383 decreased the tumor volume and size and inhibited the expressions of Wnt1, β‐catenin, and cyclin D1 at the protein level in nude mice. Collectively, miR‐383 induced apoptosis and inhibited cell viability as well as tumorigenic capacity in nude mice via regulating the Wnt/β‐catenin signaling pathway.
Long noncoding RNA uc.4 inhibits cell differentiation in heart development by altering DNA methylation
Authors: Zhang Qijun , Feng Mengwen , Zhang Hao , Xu Jia , Zhang Li , Wang Xuejun , Cheng Zijie , Qian Lingmei
Published: November 2018

In previous studies, we have demonstrated that long noncoding RNA uc.4 may influence the cell differentiation through the TGF‐β signaling pathway, suppressed the heart development of zebrafish and resulting cardiac malformation. DNA methylation plays a significant role in the heart development and disordered of DNA methylation may cause disruption of control of gene promoter. In this study, methylated DNA immunoprecipitation was performed to identify the different expression levels of methylation regions. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to identify the possible biological process and pathway that uc.4 may join, associated with Rap1 signaling pathway, gonadotropin‐releasing hormone signaling pathway, and Calcium signaling pathway. We found that the distribution of differentially methylated regions peaks was mainly located in intergenic and intron regions. Altogether, our result showed that differentially methylated genes are significantly expressed in uc.4‐overexpression cells, providing valuable data for further exploration of the role of uc.4 in heart development.
Gene therapy by lentivirus‐mediated RNA interference targeting extracellular‐regulated kinase alleviates neuropathic pain in vivo
Authors: Jia Lei , Zhang Yang , Qu Yu‐Juan , Huai Juan , Wei Hui , Yue Shou‐Wei
Published: November 2018

Backgrounds

Neuropathic pain is an abnormal pain, which is related to the activation of extracellular‐regulated kinase (ERK) signaling. This study was to investigate the effects of ERK knockdown via lentivirus‐mediated RNA interference on allodynia in rats with chronic compression of the dorsal root ganglia (DRG) and to uncover the potential mechanisms.

Methods

The model of chronic compression of the dorsal root ganglia (CCD) was established in rats by surgery. Gene silence was induced by injecting rats with lentivirus expressing ERK short hairpin RNA (shRNA). Behavioral test was performed by calculating paw withdrawal mechanical threshold (PWMT) and thermal paw withdrawal latency (TPWL).

Results

We firstly generated lentivirus expressing ERK shRNA to downregulate ERK gene expression both in vitro and in vivo by using Western blot analysis and quantitative reverse transcription polymerase chain reaction. In CCD, ERK mRNA, and protein levels in DRG neurons were dramatically increased, accompanied with decreased PWMT and TPWL. Lentivirus‐mediated RNA interference decreased ERK gene expression in DRG neurons and normalized the PWMT and TPWL in CCD rats, but not in rats infected with lentivirus expressing negative control shRNA. Further, calcium responses of DRG neurons to the hypotonic solution and 4α‐phorbol 12,13‐didecanoate were enhanced in CCD rats, which were suppressed by lentivirus‐mediated ERK gene silence. Finally, the levels of transient receptor potential vanilloid 4 gene expressions in DRG neurons and L4 to L5 spinal cord isolated from CCD rats were dramatically upregulated, which were reversed by lentivirus‐mediated ERK gene knockdown.

Conclusion

Lentivirus‐mediated RNA interference (RNAi) silencing targeting ERK might reverse CCD‐induced neuropathic pain in rats through transient receptor potential vanilloid 4.
TGFβ mediates collagen production in human CRSsNP nasal mucosa‐derived fibroblasts through Smad2/3‐dependent pathway and CTGF induction and secretion
Authors: Shieh Jiunn‐Min , Tsai Yih‐Jeng , Chi Jessie Chao‐Yun , Wu Wen‐Bin
Published: November 2018

Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue remodeling and fibrosis. Transforming growth factor‐β (TGF‐β) is considered a master switch in the induction of the profibrotic program which can induce fibroblasts to synthesize and contract extracellular matrix (ECM) proteins. A previous study has shown TGF‐β1 signaling and collagen overproduction in the CRSsNP, but the responsible cells and mechanism of action remain unclear. Therefore, this study was aimed to investigate the relationship between TGF‐β1 stimulation and collagen expression and to explore the role of connective tissue growth factor (CTGF) during the remodeling process using human CRSsNP nasal mucosa tissues and mucosa‐derived fibroblasts as main materials. We found that TGF‐β1 and its isoforms could promote collagen protein expression. Concomitantly, TGF‐β1 caused CTGF expression and secretion. An addition of exogenous CTGF to fibroblasts also caused collagen expression. In accordance with these observations, TGF‐β1, CTGF, and collagen were highly expressed in the subepithelial stroma region of CRSsNP nasal mucosa, as determined by immunohistochemistry. The TGF‐β1‐mediated collagen expression could be blocked by actinomycin D and SIS3, suggesting that the induction was through transcriptional regulation and Smad2/3‐dependent pathway. Finally, we demonstrated that CTGF small interfering RNA knockdown led to a substantial decrease in TGF‐β1‐mediated collagen expression. Collectively, our results provide first and further evidence that TGF‐β1 mediates collagen expression–production through a canonical Smad2/3‐dependent pathway and CTGF induction and secretion in human nasal fibroblasts. Moreover, TGF‐β1, CTGF, and collagen are highly expressed in human CRSsNP nasal mucosa specimens, suggesting their roles in tissue remodeling during CRSsNP progression.
A review of the molecular pathways mediating the improvement in diabetes mellitus following caloric restriction
Authors: Yaribeygi Habib , Atkin Stephen L. , Ramezani Majid , Sahebkar Amirhossein
Published: November 2018

Lifestyle modification is the cornerstone of diabetes prevention and treatment. Weight loss through caloric restriction (CR) is effective in improving glycemic control, though it is difficult for patients to follow in practice, and remains critical to achieve optimal glucose homeostasis. In this review, we look at what is known about the molecular pathways involved in CR‐induced insulin sensitivity and improved insulin resistance.
Pattern of cerebral blood flow and the interrelationship of vascular parameters of transcranial Doppler imaging in children with sickle cell disease
Authors: Asbeutah Akram M. , AlMajran Abdullah A. , Adekile Adekunle
Published: November 2018

Purpose

We assessed the pattern of cerebral blood flow and the relationship between the different transcranial Doppler imaging (TCDI) vascular parameters in children with sickle cell disease (SCD).

Methods

Forty‐three SCD pediatric patients with a stable condition (21 HbSS, 19 HbSβ0 Thal, and 3 HbSD), aged 10.1 ± 3.9 years were studied. A control group of 26 with age and sex‐matched, were included for comparison. TCDI scanning was carried out using a phased array transducer of 1‐3 MHz through the trans‐temporal window. Peak systolic velocity (PSV), end diastolic velocity (EDV), time‐averaged mean of the maximum velocity (TAMxV), pulsatility index (PI), and resistive index (RI) were in the anterior circle of Willis vessels and posterior cerebral artery.

Results

The highest mean ± SD values for the middle cerebral artery PSV, EDV, TAMxV, PI, and RI were 130.30 + 26.5, 145.0 ± 21.9; 58.60 + 13.70, 67.90 ± 13.3; 84.90 + 14.50, 94.80 ± 17.9; 0.95 + 0.20, 0.80 ± 0.20; 0.58 + 0.09, 0.50 ± 0.10 in the control and SCD groups, respectively. Independent t‐test showed significant difference (P < .05) for all vascular parameters in all vessels in each side between both groups. There was a positive significant correlation between TAMxV, PSV, and EDV (P = .001, r = .96), and a negative significant correlation between TAMxV and PI in the SCD group (P = .001, r = −.46) but not in the control group (P > .05, r = −.62).

Conclusions

There was a direct relationship between TAMxV and PSV and EDV, and an inverse relationship between TAMxV and PI in a group of SCD patients with normal TCDI values.
One‐pot Synthesis of Novel 3‐(Aryl(heteroarylamino)methyl)‐2H‐chromen‐2‐one Derivatives
Authors: Olyaei Abolfazl , Dortaj Elham , Khoeiniha Reyhaneh , Rajabi Fatemeh
Published: November 2018

A series of novel benzyl heteroarylamino coumarin derivatives were synthesized using one‐pot three‐component coupling reaction of 4‐hydroxycoumarin, aromatic aldehydes, and 2‐aminopyridines catalyzed by formic acid. A wide range of functional groups was tolerated in the developed protocol. The condensed products were obtained in high to excellent yields in CH3CN under reflux conditions. The present approach possesses several advantages due to its simplicity, short reaction time, high to excellent yield, clean and easy work‐up, and very easy purification of products by nonchromatographic methods.
MgO NPs Catalyzed Eco‐friendly Reaction: A Highly Effective and Green Approach for the Multicomponent One‐pot Synthesis of Polysubstituted Pyridines using 2‐Aminobenzothiazole
Authors: Gandhi Divyani , Agarwal Shikha
Published: November 2018

A one‐pot multicomponent green and environmentally friendly synthesis of 5‐amino‐3‐benzothiazol‐2‐yl‐7‐(phenyl)‐2‐phenyl‐2,3‐dihydro‐thiazolo[4,5‐b]pyridine‐6‐carbonitrile via Knoevenagel condensation followed by Michael addition has been described in the presence of a green, low‐cost, mild, and efficient magnesium oxide as the heterogeneous base catalyst. The present methodology has attractive features such as excellent product yields, environmentally benign milder reaction conditions, use of nontoxic organic solvents, and easily recoverable and reusable nanocatalyst. The synthesized compounds have been confirmed by spectral analysis (Fourier transform infrared, 1H‐NMR, 13C‐NMR, and mass spectrometry).
An efficient method for synthesizing dimethylsulfonio‐34S‐propionate hydrochloride from 34S8
Authors: Wirth Joseph S. , Whitman William B.
Published: November 2018

Dimethylsulfoniopropionate (DMSP, (2‐carboxyethyl)dimethylsulfonium) is a highly abundant compound in marine environments. As a precursor to the climatically active gas, dimethylsulfide (DMS), DMSP connects the marine and terrestrial sulfur cycles. However, the fate of DMSP in microbial biomass is not well understood as only a few studies have performed isotopic labeling experiments. A previously published method synthesized 34S‐labeled DMSP from 34S8, but the efficiency was only 26% and required five separate reactions, expensive reagents, and purification of the products of each reaction. In this study, a method of synthesizing 34S‐labeled DMSP from 34S8 is described. Improvements include elemental steps, inexpensive reagents, purification of only one intermediate, and less time to complete. The efficiency of this method is 65% and results in pure DMSP with more than 98% isotope enrichment as determined by 1H‐nuclear magnetic resonance (NMR) and gas chromatography–mass spectrometry (GC–MS).
Failure analysis on synergistic effect of erosion and corrosion on failed fittings in specialty chemical plant. Part II: Control valve
Authors: Yang Xiao‐Lei , Wang Sheng‐Hui , Fei Jing‐Lu , Gong Yi , Yang Zhen‐Guo
Published: November 2018

Failure analysis was carried out on a control valve in the steam system of a specialty chemical plant. Comprehensive analyses were conducted to investigate the operating conditions, base materials, macroscopic, and microscopic morphologies of the failed steam control valve and a computational fluid dynamic model was also adopted. The results showed that the synergistic effect of electrochemical corrosion favored by chlorides and two phase flow erosion accounted for the premature failure of the steam control valve. Considering the fact that the valve was designed by a German company, assembled by an American company and used in a Chinese company, our failure analysis seems to be crucial for the imputation of the responsibility. The failure mechanisms were discussed and the relevant countermeasures were proposed to prevent the occurrence of similar failure again.
Fast food, ads, and taste in a Russian child’s mind
Authors: Effertz Tobias , Teichert Thorsten , Tsoy Marina
Published: November 2018

Research demonstrates that brands can influence children’s food preferences and potentially contribute to unhealthy consumption patterns. This article extends this line of research by investigating the complex and interacting effects of food brand marketing on experienced taste. The empirical field in a remote Russian town enabled the assessment of branding effects when entering a newly established market. Examining the combination of various advertisement features with emotional brand elicitation, we derive hypotheses about the interplay of brands and advertisement components linked to the perceived taste of a fast food meal. In Novosibirsk, Russia, 778 children and adolescents aged 10–18 years were exposed to fast food advertisements with real and imaginary brand logos and varying advertising claims. The advertisements consisted of a warning, an exaggerated credence claim, or both. A subsequently offered fast food meal—a portion of French fries—was experimentally varied and prepared to be either healthier but less tasty and unsalted, or less healthy but tastier and salted. The findings verify strong and positive brand effects on children’s taste satisfaction. Warnings in advertisements “worked” only for novel fast food brands by negatively affecting taste satisfaction, but increased taste satisfaction when applied in advertisements for established brands. Single credence claims did not improve the taste experience, but counteracted the negative effects of warnings for novel brands. Finally, the established brand influenced taste satisfaction positively when the fries were saltier. The findings reveal various opportunities for fast food marketing to artificially create taste satisfaction for potentially unhealthy food. Public health strategies that focus on advertising claim restrictions should be reconsidered in the context of possible evasion strategies of the food industry and counter‐effects of warnings among strong fast food brands.
Four‐bit instantaneous frequency measurement systems based on frequency selective surfaces
Authors: Pinheiro Giordano J. , de Oliveira Manuelle R. T. , Silva Filho Hawson V. H. , de Melo Marcos T. , Neto Alfredo G. , de Sousa Thayuan R.
Published: November 2018

This paper presents four frequency selective surfaces (FSSs) to be used in an instantaneous frequency measurement (IFM) systems. The FSS based on simple dipoles have a frequency response corresponding to the characteristics of frequency discriminators. An IFM system with 4‐bits is shown with resolution around 300 MHz. The system contains 16 distinct frequency sub‐bands between 3.21 and 8.75 GHz. CST software simulations and measurements of insertion loss are presented and compared with theoretical results to provide the binary codes of the system.
Simultaneous NODDI and GFA parameter map generation from subsampled q‐space imaging using deep learning
Authors: Gibbons Eric K. , Hodgson Kyler K. , Chaudhari Akshay S. , Richards Lorie G. , Majersik Jennifer J. , Adluru Ganesh , DiBella Edward V.R.
Published: November 2018

Purpose

To develop a robust multidimensional deep‐learning based method to simultaneously generate accurate neurite orientation dispersion and density imaging (NODDI) and generalized fractional anisotropy (GFA) parameter maps from undersampled q‐space datasets for use in stroke imaging.

Methods

Traditional diffusion spectrum imaging (DSI) capable of producing accurate NODDI and GFA parameter maps requires hundreds of q‐space samples which renders the scan time clinically untenable. A convolutional neural network (CNN) was trained to generated NODDI and GFA parameter maps simultaneously from 10× undersampled q‐space data. A total of 48 DSI scans from 15 stroke patients and 14 normal subjects were acquired for training, validating, and testing this method. The proposed network was compared to previously proposed voxel‐wise machine learning based approaches for q‐space imaging. Network‐generated images were used to predict stroke functional outcome measures.

Results

The proposed network achieves significant performance advantages compared to previously proposed machine learning approaches, showing significant improvements across image quality metrics. Generating these parameter maps using CNNs also comes with the computational benefits of only needing to generate and train a single network instead of multiple networks for each parameter type. Post‐stroke outcome prediction metrics do not appreciably change when using images generated from this proposed technique. Over three test participants, the predicted stroke functional outcome scores were within 1–6% of the clinical evaluations.

Conclusions

Estimates of NODDI and GFA parameters estimated simultaneously with a deep learning network from highly undersampled q‐space data were improved compared to other state‐of‐the‐art methods providing a 10‐fold reduction scan time compared to conventional methods.
American Normal: Situated Theory and American Anthropological Knowledge Production
Authors: Wolf‐Meyer Matthew
Published: November 2018

Key social scientific concepts are based in local theories particular to the North Atlantic, and the United States especially, and have been exported by anthropologists to analyze diverse ethnographic contexts despite the lack of interrogation of their status as local, American theories. In this article, I address this situation by focusing on the elaboration of American normalcy in its present moment, dependent upon a lay reconfiguration of “ideology,” “hegemony,” and “history.” In advancing this analysis, I focus on popular media journalism and its analysis of the Trump presidency. My approach is bifocal, at once focusing on the history of these Marxian concepts while attending to their permutations in the present. Focusing on these concepts and their relation to ideas of the individual and institutions opens up possibilities for the symmetrical analysis of knowledge production practices and everyday actions of popular and expert communities, and lays the foundation for the cultural anthropology of the U.S. to critique contemporary U.S. politics as well as social science knowledge production and its circulation.
Effects of a Community‐Based Diabetes Prevention Program for Latino Youth with Obesity: A Randomized Controlled Trial
Authors: Soltero Erica G. , Olson Micah L. , Williams Allison N. , Konopken Yolanda P. , Castro Felipe G. , Arcoleo Kimberly J. , Keller Colleen S. , Patrick Donald L. , Ayers Stephanie L. , Barraza Estela , Shaibi Gabriel Q.
Published: November 2018

Objective

This study examined the short‐ and long‐term effects of a community‐based lifestyle intervention among Latino youth with obesity.

Methods

Latino adolescents (14‐16 years old) were randomized to a 3‐month lifestyle intervention (n = 67) or comparison control (n = 69) and followed for 12 months. The intervention included weekly nutrition and health classes delivered to groups of families and exercise sessions (3 days/week) delivered to groups of adolescents. Comparison youth received laboratory results and general health information. Primary outcomes included insulin sensitivity and weight‐specific quality of life (QoL) with secondary outcomes of BMI percentile (BMI%), waist circumference, and percent body fat.

Results

At 3 months, youth in the intervention group exhibited significant increases in insulin sensitivity (P < 0.05) and weight‐specific QoL (P < 0.001), as well as reductions in BMI%, waist circumference, and percent body fat compared with controls. Increases in weight‐specific QoL and reductions in BMI% and percent body fat remained significant at 12 months (P < 0.001), while changes in insulin sensitivity did not. In a subsample of youth with prediabetes at baseline, insulin sensitivity (P = 0.01), weight‐specific QoL (P < 0.001), and BMI% (P < 0.001) significantly improved at 3 months.

Conclusions

Lifestyle intervention can improve cardiometabolic and psychosocial health in a vulnerable population of Latino adolescents at high risk for developing type 2 diabetes.
Only strongly enhanced residual FDG uptake in early response PET (Deauville 5 or qPET ≥ 2) is prognostic in pediatric Hodgkin lymphoma: Results of the GPOH‐HD2002 trial
Authors: Kurch L. , Hasenclever D. , Kluge R. , Georgi T. , Tchavdarova L. , Golombeck M. , Sabri O. , Eggert A. , Brenner W. , Sykora K.W. , Bengel F.M. , Rossig C. , Körholz D. , Schäfers M. , Feuchtinger T. , Bartenstein P. , Ammann R.A. , Krause T. , Urban C. , Aigner R. , Gattenlöhner S. , Klapper W. , Mauz‐Körholz C.
Published: November 2018

Purpose

In 2014, we published the qPET method to quantify fluorodeoxyglucose positron emission tomography (FDG‐PET) responses. Analysis of the distribution of the quantified signals suggested that a clearly abnormal FDG‐PET response corresponds to a visual Deauville score (vDS) of 5 and high qPET values ≥ 2. Evaluation in long‐term outcome data is still pending. Therefore, we analyzed progression‐free survival (PFS) by early FDG‐PET response in a subset of the GPOH‐HD2002 trial for pediatric Hodgkin lymphoma (PHL).

Patients/Methods

Pairwise FDG‐PET scans for initial staging and early response assessment after two cycles of chemotherapy were available in 93 PHL patients. vDS and qPET measurement were performed and related to PFS.

Results

Patients with a qPET value ≥ 2.0 or vDS of 5 had 5‐year PFS rates of 44%, respectively 50%. Those with qPET values < 2.0 or vDS 1 to 4 had 5‐year PFS rates of 90%, respectively 80%. The positive predictive value of FDG‐PET response assessment increased from 18% (9%; 33%) using a qPET threshold of 0.95 (vDS ≤ 3) to 30% (13%; 54%) for a qPET threshold of 1.3 (vDS ≤ 4) and to 56% (23%; 85%) when the qPET threshold was ≥ 2.0 (vDS 5). The negative predictive values remained stable at ≥92% (CI: 82%; 98%).

Conclusion

Only strongly enhanced residual FDG uptake in early response PET (vDS 5 or qPET ≥ 2, respectively) seems to be markedly prognostic in PHL when treatment according to the GPOH‐HD‐2002 protocol is given.
Synthesis of 3a‐hydroxyhexahydropyrrolo[2,3‐B]Indole‐2‐carboxamide, an oxidation product of tryptophan present in natural products
Authors: Blanc Antoine , Perrin David M.
Published: November 2018

The 3a‐hydroxyhexahydropyrrolo[2,3‐b]indole‐2‐carboxamide (HO‐HPIC) is formed from the oxidation of tryptophan residues and is well represented in peptide‐based natural products. These natural products exhibit potential medicinal activities and thus have caught the attention of chemists and biologists over the past few years. Considerable effort has been marshaled toward the synthesis of HO‐HPIC‐containing natural products, but only a few of these peptides have been successfully synthetically prepared. This review briefly describes a few choice natural products containing the HO‐HPIC motif, summarizes the biological activities and synthetic routes of selected natural compounds containing HO‐HPIC, and emphasizes the use of dimethyldioxirane (DMDO) in the oxidation of tryptophan and its derivatives to HO‐HPIC‐containing motifs.
Everyday protective buffering predicts intimacy and fear of cancer recurrence in couples coping with early‐stage breast cancer
Authors: Perndorfer Christine , Soriano Emily C. , Siegel Scott D. , Laurenceau Jean‐Philippe
Published: November 2018

Objective

Patient and spouse/partner mutual self‐disclosure is central for maintaining intimacy and cognitive processing when transitioning to life after cancer. Protective buffering inhibits self‐disclosure and is defined as efforts to protect one's partner from upset and burden by hiding or denying cancer‐related concerns. Intimacy and fear of cancer recurrence (FCR) are important determinants of individual and couple adaptation following cancer. Links between protective buffering and intimacy have not been examined in the context of daily life, and links with FCR have not been studied. We hypothesized that protective buffering is associated with decreased intimacy and increased FCR at a daily, within‐person level.

Methods

Sixty‐nine early‐stage breast cancer (BC) survivors and their spouses completed electronic diaries for 21 consecutive days at the end of adjuvant treatment. Patients and spouses reported on daily protective buffering, intimacy, and FCR. Dyadic multilevel path modeling was used to estimate within‐person effects. Patient and spouse protective buffering on one's own as well as one's partner's same‐day intimacy and FCR were examined, controlling for previous levels of intimacy and FCR.

Results

Protective buffering was associated with decreased intimacy and increased FCR for the individual reporting buffering that same day. Patient and spouse protective buffering was also linked to decreased intimacy for her/his partner that same day. Moreover, patient protective buffering predicted increased spouse FCR that same day.

Conclusions

Findings supported a daily, within‐person link between buffering, intimacy, and FCR, suggesting open disclosure of cancer‐related concerns may be a relevant target for interventions for adaptation to BC.