bluuebunny/crossref_metadata_2025 huggingface dataset:
Formal training in cardiotocograph interpretation of healthcare practitioners improves interpretation: A prospective descriptive analytical study in a resource constrained setting
Authors: Goldman Bernardus , Naidoo Thinagrin
Published: December 2020

Objective

To evaluate the effect of structured training on the cardiotocograph (CTG) interpretation skills of healthcare workers (HCWs) involved in obstetric care in a recourse constrained setting.

Method

In all, 218 HCWs completed pre‐ and post‐intervention questionnaires. The intervention involved structured teaching on technical aspects of CTG monitoring, fetal physiology, and adaptation to stress, and a holistic approach to interpretation. Descriptive statistics were used to summarize demographic characteristics, frequencies, and percentages for categorical data.

Results

Only 26.2% of participants felt that their pre‐graduate training was adequate; this was reflected by the poor baseline knowledge in CTG interpretation (56% misinterpreted) and lack of knowledge regarding technical aspects of CTG monitoring in 48.8% of participants. The training session led to a 65% improvement in technical aspects and interpretation. Those HCWs not receiving continuous training showed a more significant improvement (P  < 0.001) and there was a 100% improvement in knowledge regarding the required documentation before commencing monitoring. Most (99.5%) HCWs acknowledged an improvement in knowledge, and 96.2% would participate in similar mandatory education sessions.

Conclusion

These findings highlight the fact that training in CTG monitoring is warranted and desired by HCWs. It also supports the implementation of structured CTG education in resource‐constrained settings.
Role of alkali metal oxide type on the degradation and in vivo biocompatibility of soda‐lime‐borate bioactive glass
Authors: Omar Areg E. , Ibrahim Ahlam M. , Abd El‐Aziz Tamer H. , Al‐Rashidy Zainab M. , Farag Mohammad M.
Published: December 2020

In this work, it is the first time to study the effect of replacing of Na2O by a fixed amount of Li2O or K2O in soda‐lime‐borate glass on its in vivo biocompatibility. The glass composition was based on xM2O‐20x Na2O20 CaO60 B2O3, (wt %), where, M2OLi2O and K2O, and consequently, samples encoded BN100, BK50, and BL50. The degradation test was carried out in 0.25 M K2HPO4 solution. The in vivo test was performed in the femoral bone defect of Sprague–Dawley adult male rat. Following up bone formation was conducted by the histological analyses and bone formation markers (alkaline phosphatase [ALP] and osteocalcin [OCN]). Furthermore, the glass effect on the liver and kidney functions was addressed in this study using (alanine transaminase [ALT] and aspartate transaminase [AST]) and (urea and creatinine), respectively. The results of the degradation test showed that the glass dissolution rate was increased by incorporating of K2O, and its ion release was occurred by a diffusion‐controlled process. Moreover, in vivo bioactivity test showed that serum activity of ALP, OCN level, and the newly formed bone was higher in BL50‐implanted group than that of BN100 andBK50at 3 w and 6 w post‐surgery. As well as, implantation of all glass samples in the femoral bone defect did not alter the liver and kidney functions. In conclusion, the synthesized borate glass was well served as a controlled delivery system for Li+ ion release, which enhanced bone formation as shown from the bone formation markers (ALP and OCN).
Electron injection for aromatic metamorphosis of indole
Authors: Yorimitsu Hideki
Published: December 2020

Aromatic metamorphosis, endocyclic transformations of aromatic compounds, has been emerging as a new synthetic strategy in organic synthesis. This counterintuitive strategy necessitates very powerful reactions that can surmount aromaticity and the strong carbon–heteroatom bonds of the heteroaromatic rings. This Short Account describes the development of the currently most powerful elementary reaction for aromatic metamorphosis, which is electron injection from lithium metal. Exceptionally robust and aromatic N‐phenylindole is subjected to the electron injection, resulting in the formation of the corresponding dianionic intermediate through reductive ring‐opening. A trapping reaction of the dianionic intermediate with organoboronic acid pinacol esters provides benzazaborines, which are attractive BN‐isosteres of naphthalenes. The electron injection helps establishing aromatic metamorphosis as a reliable synthetic methodology to provide novel useful molecules.
Katanin P60 and P80 in papillary thyroid carcinoma patients: Indicators for exacerbated tumor features and worse disease‐free survival
Authors: Chen Qinggui , Lin Fusheng , Lin Ende , Huang Qinghe , Wu Guoyang
Published: December 2020

Background

This study aimed to explore the clinical implications of katanin P60 and P80 (katanin P60/P80) regarding their correlations with clinicopathological features and survival profiles in papillary thyroid carcinoma (PTC) patients.

Methods

Tumor tissue and paired adjacent tissue specimens were obtained from 172 PTC patients who underwent lobectomy or thyroidectomy. Besides, immunohistochemistry assay and immunoreactive (IR) score (multiplying staining intensity score by density score) were used to determine katanin P60/P80 expressions. According to IR score (from 0 ~ 12), katanin P60/P80 expressions were classified as low (IR score 0 ~ 3) and high (IR score 4 ~ 12) expressions.

Results

Both katanin P60/P80 expressions were highly expressed in tumor tissue compared with adjacent tissue. Besides, tumor katanin P60 expression positively correlated with tumor katanin P80 expression. Tumor katanin P60 high expression correlated with larger tumor size, extrathyroidal invasion, advanced pT stage, pN stage, and pTNM stage, while no correlation of tumor katanin P60 expression with age or gender was observed; tumor katanin P80 high expression correlated with advanced pN stage and pTNM stage, whereas there was no correlation of tumor katanin P80 expression with age, gender, tumor size, extrathyroidal invasion, or pT stage. Furthermore, both tumor katanin P60/P80 high expressions correlated with shorter accumulating disease‐free survival. As for overall survival (OS), neither tumor katanin P60 nor P80 expression correlated with OS.

Conclusion

Katanin P60/P80 measurement might assist with tumor management and prognosis surveillance in PTC patients.
Luteolin enhances the antitumor efficacy of oncolytic vaccinia virus that harbors IL‐24 gene in liver cancer cells
Authors: Wang Chunming , Li Qiang , Xiao Boduan , Fang Huiling , Huang Biao , Huang Fang , Wang Yigang
Published: December 2020

Background

Interleukin 24 (IL‐24) is an IL‐10 family member and a secreted cytokine characterized by cancer‐targeted toxicity and can activate apoptosis by sensitizing cancer cells to chemotherapy. Cytotoxic effects of luteolin on different types of cancer cells suppress their growth by acting on the components of the apoptosis signaling cascade. Therefore, our study aimed to prove whether oncolytic vaccinia virus (VV) that harbors IL‐24 (VV‐IL‐24) combine with luteolin exerts a synergistic inhibitory effect in liver cancer cells.

Methods

Impacts on cell viability of VV‐IL‐24 and luteolin were assessed by MTT in various liver cancer cell lines. Then, liver cancer cell apoptosis was analyzed via flow cytometry and Western blotting. Besides, the MHCC97‐H xenograft mouse model was employed as a means of assessing in vivo antitumor efficacy.

Results

MTT assay confirmed that the combination treatment decreased liver cancer cells viability to a greater degree than treatment with VV‐IL‐24 or luteolin alone. Flow cytometry and Western blot assay proved that VV‐IL‐24 plus luteolin induced more liver cancer cells apoptosis than single treatment. Furthermore, in the MHCC97‐H xenograft model, 15 days of treatment with VV‐IL‐24 plus luteolin inhibited tumor growth significantly more than single treatment.

Conclusion

These data confirm that the synergistic mechanism of VV‐IL‐24 and luteolin elicits a stronger tumor growth inhibition than any single therapy. Thus, the combination of VV‐IL‐24 and luteolin could provide the basis for preclinical research in the treatment of liver cancer.
Zinc finger E‐box binding homeobox 1 and atherosclerosis: New insights and therapeutic potential
Authors: Li Heng , Zou Jin , Yu Xiao‐Hua , Ou Xiang , Tang Chao‐Ke
Published: December 2020

Zinc finger E‐box binding homeobox 1 (ZEB1), an important transcription factor belonging to the ZEB family, plays a crucial role in regulating gene expression required for both normal physiological and pathological processes. Accumulating evidence has shown that ZEB1 participates in the initiation and progression of atherosclerotic cardiovascular disease. Recent studies suggest that ZEB1 protects against atherosclerosis by regulation of endothelial cell angiogenesis, endothelial dysfunction, monocyte‐endothelial cell interaction, macrophage lipid accumulation, macrophage polarization, monocyte‐vascular smooth muscle cell (VSMC) interaction, VSMC proliferation and migration, and T cell proliferation. In this review, we summarize the recent progress of ZEB1 in the pathogenesis of atherosclerosis and provide insights into the prevention and treatment of atherosclerotic cardiovascular disease.
Ruxolitinib is effective in the treatment of a patient with refractory T‐ALL
Authors: Jaramillo Sonia , Hennemann Hannah , Horak Peter , Teleanu Veronica , Heilig Christoph E. , Hutter Barbara , Stenzinger Albrecht , Glimm Hanno , Goeppert Benjamin , Müller‐Tidow Carsten , Fröhling Stefan , Schönland Stefan , Schlenk Richard F.
Published: December 2020

T‐cell acute lymphoblastic leukemia (T‐ALL) is a rare, aggressive T‐cell malignancy. Chemotherapy alone cures only 25‐45% of the cases, thus, novel treatment agents and strategies are urgently needed. We assessed the efficacy of ruxolitinib in a patient with a cutaneous relapse after allogeneic blood cell transplantation of a refractory T‐ALL with a Janus kinase 3 (JAK3) mutation. In this case report, we were able to show the potential benefit of the JAK inhibitor ruxolitinib in JAK3‐mutated refractory T‐ALL and emphasize the importance of integrating molecular markers in current treatment decision making for patients with T‐ALL.
Thorium chelators for targeted alpha therapy: Rapid chelation of thorium‐226
Authors: Ferrier Maryline G. , Li Yawen , Chyan Ming‐Kuan , Wong Roger , Li Lily , Spreckelmeyer Sarah , Hamlin Donald K. , Mastren Tara , Fassbender Michael E. , Orvig Chris , Wilbur D. Scott
Published: December 2020

One of the main challenges in targeted alpha therapy is assuring delivery of the α‐particle dose to the targeted cells. Thus, it is critical to identify ligands for α‐emitting radiometals that will form complexes that are very stable, both in vitro and in vivo. In this investigation, thorium‐227 (t1/2 = 18.70 days) chelation of ligands containing hydroxypyridinonate (HOPO) or picolinic acid (pa) moieties and the stability of the resultant complexes were studied. Chelation reactions were followed by reversed‐phased HPLC and gamma spectroscopy. Studies revealed that high 227Th chelation yields could be obtained within 2.5 h or less with ligands containing four Me‐3,2‐HOPO moieties, 1 (83%) and 2 (65%), and also with ligands containing pa moieties, H4octapa 3 (65%) and H4py4pa 6 (87%). No reaction occurred with H4neunpa‐p‐Bn‐NO2 4, and the chelation reaction with another pa ligand H4pypa 5 gave inconsistent yields with a very broad radio‐HPLC peak. The ligands spermine‐(Me‐3,2‐HOPO)4 1, H4octapa 3, and H4py4pa 6 had high stability (i.e., 87% of 227Th still bound to the ligand) in phosphate‐buffered saline at room temperature over a 6‐day period. Preliminary studies with ligand 6 demonstrated efficient chelation of thorium‐226 (t1/2 = 30.57 min) when heated to 80°C for 5 min.
PGPR‐mediated induction of systemic resistance and physiochemical alterations in plants against the pathogens: Current perspectives
Authors: Meena Mukesh , Swapnil Prashant , Divyanshu Kumari , Kumar Sunil , Harish  , Tripathi Yashoda Nandan , Zehra Andleeb , Marwal Avinash , Upadhyay Ram Sanmukh
Published: December 2020

Plant growth‐promoting rhizobacteria (PGPR) are diverse groups of plant‐associated microorganisms, which can reduce the severity or incidence of disease during antagonism among bacteria and soil‐borne pathogens, as well as by influencing a systemic resistance to elicit defense response in host plants. An amalgamation of various strains of PGPR has improved the efficacy by enhancing the systemic resistance opposed to various pathogens affecting the crop. Many PGPR used with seed treatment causes structural improvement of the cell wall and physiological/biochemical changes leading to the synthesis of proteins, peptides, and chemicals occupied in plant defense mechanisms. The major determinants of PGPR‐mediated induced systemic resistance (ISR) are lipopolysaccharides, lipopeptides, siderophores, pyocyanin, antibiotics 2,4‐diacetylphoroglucinol, the volatile 2,3‐butanediol,N‐alkylated benzylamine, and iron‐regulated compounds. Many PGPR inoculants have been commercialized and these inoculants consequently aid in the improvement of crop growth yield and provide effective reinforcement to the crop from disease, whereas other inoculants are used as biofertilizers for native as well as crops growing at diverse extreme habitat and exhibit multifunctional plant growth‐promoting attributes. A number of applications of PGPR formulation are needed to maintain the resistance levels in crop plants. Several microarray‐based studies have been done to identify the genes, which are associated with PGPR‐induced systemic resistance. Identification of these genes associated with ISR‐mediating disease suppression and biochemical changes in the crop plant is one of the essential steps in understanding the disease resistance mechanisms in crops. Therefore, in this review, we discuss the PGPR‐mediated innovative methods, focusing on the mode of action of compounds authorized that may be significant in the development contributing to enhance plant growth, disease resistance, and serve as an efficient bioinoculants for sustainable agriculture. The review also highlights current research progress in this field with a special emphasis on challenges, limitations, and their environmental and economic advantages.
Cartilage articulation exacerbates chondrocyte damage and death after impact injury
Authors: Ayala Steven , Delco Michelle L. , Fortier Lisa A. , Cohen Itai , Bonassar Lawrence J.
Published: December 2020

Posttraumatic osteoarthritis (PTOA) is typically initiated by momentary supraphysiologic shear and compressive forces delivered to articular cartilage during acute joint injury and develops through subsequent degradation of cartilage matrix components and tissue remodeling. PTOA affects 12% of the population who experience osteoarthritis and is attributed to over $3 billion dollars annually in healthcare costs. It is currently unknown whether articulation of the joint post‐injury helps tissue healing or exacerbates cellular dysfunction and eventual death. We hypothesize that post‐injury cartilage articulation will lead to increased cartilage damage. Our objective was to test this hypothesis by mimicking the mechanical environment of the joint during and post‐injury and determining if subsequent joint articulation exacerbates damage produced by initial injury. We use a model of PTOA that combines impact injury and repetitive sliding with confocal microscopy to quantify and track chondrocyte viability, apoptosis, and mitochondrial depolarization in a depth‐dependent manner. Cartilage explants were harvested from neonatal bovine knee joints and subjected to either rapid impact injury (17.34 ± 0.99 MPa, 21.6 ± 2.45 GPa/s), sliding (60 min at 1 mm/s, under 15% axial compression), or rapid impact injury followed by sliding. Explants were then bisected and fluorescently stained for cell viability, caspase activity (apoptosis), and mitochondria polarization. Results show that compared to either impact or sliding alone, explants that were both impacted and slid experienced higher magnitudes of damage spanning greater tissue depths.
Naproxen treatment inhibits articular cartilage loss in a rat model of osteoarthritis
Authors: Paglia David N. , Kanjilal Deboleena , Kadkoy Yazan , Moskonas Spiro , Wetterstrand Charlene , Lin Anthony , Galloway Joseph , Tompson Jeffrey , Culbertson Maya D. , O'Connor J. Patrick
Published: December 2020

The effects of naproxen, a nonsteroidal anti‐inflammatory drug (NSAID), on articular cartilage degeneration in female Sprague–Dawley rats was examined. Osteoarthritis (OA) was induced by destabilization of the medial meniscus (DMM) in each knee. Rats were treated with acetaminophen (60 mg/kg), naproxen (8 mg/kg), or 1% carboxymethylcellulose (placebo) by oral gavage twice daily for 3 weeks, beginning 2 weeks after surgery. OA severity was assessed by histological Osteoarthritis Research Society International (OARSI) scoring and by measuring proximal tibia cartilage depth using contrast enhanced µCT (n = 6 per group) in specimens collected at 2, 5, and 7 weeks after surgery as well as on pristine knees. Medial cartilage OARSI scores from the DMM knees of naproxen‐treated rats were statistically lower (i.e., better) than the medial cartilage OARSI scores from the DMM knees of placebo‐treated rats at 5‐weeks (8.7 ± 3.6 vs. 13.2 ± 2.4, p = 0.025) and 7‐weeks (9.5 ± 1.2 vs. 12.5 ± 2.5, p = 0.024) after surgery. At 5 weeks after DMM surgery, medial articular cartilage depth in the proximal tibia specimens was significantly greater in the naproxen (1.78 ± 0.26 mm, p = 0.005) and acetaminophen (1.94 ± 0.12 mm, p < 0.001) treated rats as compared with placebo‐treated rats (1.34 ± 0.24 mm). However, at 7 weeks (2 weeks after drug withdrawal), medial articular cartilage depth for acetaminophen‐treated rats (1.36 ± 0.29 mm) was significantly reduced compared with specimens from the naproxen‐treated rats (1.88 ± 0.14 mm; p = 0.004). The results indicate that naproxen treatment reduced articular cartilage degradation in the rat DMM model during and after naproxen treatment.
Comparative proteomic analysis of three Lactobacillus plantarum strains under salt stress by iTRAQ
Authors: Luo Xue , Li Mo , Zhang Henan , Yan Danli , Ji Shuaiqi , Wu Rina , Chen Yongfu
Published: December 2020

BACKGROUND

Lactobacillus plantarum, a common species of lactic acid bacteria, is used to improve the flavor of traditional fermented food. Under salt stress, different strains of L. plantarum can respond differently. In this work, proteomics and bioinformatics analysis of L. plantarum strains (ATCC14917, FS5‐5, and 208) grown under salt stress (240 g L−1 sodium chloride (NaCl)) were investigated based on the isobaric tags for relative and absolute quantitation method.

RESULTS

Although 171 differentially expressed proteins (DEPs) were observed, only 44, 57, and 112 DEPs were identified in the strains ATCC14917, FS5‐5, and 208 respectively. There were 33, 191, and 179 specific DEPs in ATCC14917 versus FS5‐5, in 208 versus FS5‐5, and in strain 208 versus ATCC14917 in 240 g L−1 NaCl. These DEPs indicate that the three strains, from pickles, fermented soybean paste, and fermented milk, may have different salt stress responses. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis showed that most DEPs observed were involved in protein biosynthesis, nucleotide metabolism, and sugar metabolism. Twenty‐six significantly different DEPs that were possibly associated with salt response were selected and further analyzed for gene expression level and pattern by quantitative reverse transcription polymerase chain reaction. Pyruvate kinase and cysteine desulfurase had similar expression patterns in all three strains; glutamate decarboxylase expression was upregulated in FS5‐5 and significantly upregulated in strain 208; RNA polymerase subunit alpha was downregulated in FS5‐5 but upregulated in strain 208.

CONCLUSIONS

These results also showed that the salt stress response of strain 208 may involve higher numbers of genes than the other strains. This research provides a theoretical basis for improvement of salt tolerance of L. plantarum in industrial production. © 2020 Society of Chemical Industry
Integrating consumer perception in the selection of purple‐skin sweet potato cultivars
Authors: Lado Joanna , Vicente Esteban , Moltini Ana Inés , Alcaire Florencia , Ares Gastón
Published: December 2020

BACKGROUND

Sweet‐potato breeding programs need to integrate sensory characterization and hedonic perception to provide global markets with widely accepted products. The present work aimed to characterize a series of purple‐skin sweet potatoes differing in flesh coloration (from pale yellow to slight orange) from a sensory and physicochemical perspective. Uruguayan consumers' perceptions of the genotypes were also explored. Special focus was placed on the influence of flesh color on consumers' expectations and hedonic perception of purple‐skin sweet potatoes.

RESULTS

Sensory characterization based on projective mapping showed that the evaluated genotypes largely differed in their sensory characteristics in terms of flavor, texture, and color. Soluble solids and the concentration of individual sugars were not good predictors of sensory quality. In the appearance evaluation, consumers associated orange flesh with positive expected sensory characteristics and stronger liking. Flavor (sweetness and typical flavor) and texture (creaminess) were identified as key characteristics influencing consumers' liking and description of sweet‐potato samples. Among purple‐skin (‘criollo or boniato’ type) genotypes, INIA Cambará was identified as the closest to the ideal sweet potato and was described with the terms sweet, tasty, creamy, and characteristic flavor.

CONCLUSION

Flesh color was identified as a key driver of consumers' sensory and hedonic expectations. Results showed that Uruguayan consumers positively value traditional purple‐skin sweet potatoes with orange flesh, as it drives positive sensory expectations. However, after tasting, flesh color does not seem to have a relevant influence on consumer liking.
Development and evaluation of poly adenosine 5′‐diphosphate‐ribose polymerase 1 immobilization‐based receptor chromatography
Authors: Dou Jianwei , Zhu Zhongbo , Li Yan , Yang Shuo , Guo Zhanzi , Li Kangle , Ren Cuicui , Huang Linhong , He Jianyu
Published: December 2020

Yanghe decoction is a traditional Chinese medicine prescription and has been used for breast cancer treatment for many years. However, the effective ingredients in the decoction have not been identified. The expression of poly(ADP‐ribose) polymerase‐1 is highly related to breast cancer. Using poly(ADP‐ribose) polymerase‐1 as a probe, we expressed the haloalkane dehalogenase‐tagged protein in BL21(DE3) E. coli, immobilized it on hexachlorocaproic acid‐modified macroporous silica gel, and established a poly(ADP‐ribose) polymerase‐1 chromatographic model. The feasibility of the model was verified by testing the retention behaviors of five drugs on the protein column. We applied the model in screening the bioactive components in yanghe decoction. Rutin, liquiritin, and a compound ([M‐H]– 681.7) were identified to be the potential bioactive ingredients. We studied the binding property between rutin and poly(ADP‐ribose) polymerase‐1 by injection amount dependent method, competitive studies, and molecular docking. We found that rutin can bind to the protein through the typical inhibitor binding site of the protein. Therefore, the chromatographic model is a useful tool to screen bioactive compounds from traditional Chinese medicine. The method is fast, reliable, and applicable to other functional proteins that can screen the potential lead compounds for the treatment of the related diseases.
Revisiting prostate cancer metabolism: From metabolites to disease and therapy
Authors: Cardoso Henrique J. , Carvalho Tiago M. A. , Fonseca Lara R. S. , Figueira Marília I. , Vaz Cátia V. , Socorro Sílvia
Published: December 2020

Prostate cancer (PCa), one of the most commonly diagnosed cancers worldwide, still presents important unmet clinical needs concerning treatment. In the last years, the metabolic reprogramming and the specificities of tumor cells emerged as an exciting field for cancer therapy. The unique features of PCa cells metabolism, and the activation of specific metabolic pathways, propelled the use of metabolic inhibitors for treatment. The present work revises the knowledge of PCa metabolism and the metabolic alterations that underlie the development and progression of the disease. A focus is given to the role of bioenergetic sources, namely, glucose, lipids, and glutamine sustaining PCa cell survival and growth. Moreover, it is described as the action of oncogenes/tumor suppressors and sex steroid hormones in the metabolic reprogramming of PCa. Finally, the status of PCa treatment based on the inhibition of metabolic pathways is presented. Globally, this review updates the landscape of PCa metabolism, highlighting the critical metabolic alterations that could have a clinical and therapeutic interest.
Continuous dependence for the Brinkman–Darcy–Kelvin–Voigt equations backward in time
Authors: Straughan B.
Published: December 2020

We show that the solution to the Brinkman–Darcy–Kelvin–Voigt equations backward in time depends Hölder continuously upon the final data. A logarithmic convexity technique is employed, and uniqueness of the solution is simultaneously achieved.
No Effect of Dietary Fish Oil Supplementation on the Recruitment of Brown and Brite Adipocytes in Mice or Humans under Thermoneutral Conditions
Authors: Maurer Stefanie F. , Dieckmann Sebastian , Lund Jens , Fromme Tobias , Hess Anne Lundby , Colson Cécilia , Kjølbæk Louise , Astrup Arne , Gillum Matthew Paul , Larsen Lesli Hingstrup , Liebisch Gerhard , Amri Ez‐Zoubir , Klingenspor Martin
Published: December 2020

Scope

Brown and brite adipocytes within the mammalian adipose organ provide non‐shivering thermogenesis and thus, have an exceptional capacity to dissipate chemical energy as heat. Polyunsaturated fatty acids (PUFA) of the n3‐series, abundant in fish oil, have been repeatedly demonstrated to enhance the recruitment of thermogenic capacity in these cells, consequently affecting body adiposity and glucose tolerance. These effects are scrutinized in mice housed in a thermoneutral environment and in a human dietary intervention trial.

Methods and results

Mice are housed in a thermoneutral environment eliminating the superimposing effect of mild cold‐exposure on thermogenic adipocyte recruitment. Dietary fish oil supplementation in two different inbred mouse strains neither affects body mass trajectory nor enhances the recruitment of brown and brite adipocytes, both in the presence and absence of a β3‐adrenoreceptor agonist imitating the effect of cold‐exposure on adipocytes. In line with these findings, dietary fish oil supplementation of persons with overweight or obesity fails to recruit thermogenic adipocytes in subcutaneous adipose tissue.

Conclusion

Thus, the authors' data question the hypothesized potential of n3‐PUFA as modulators of adipocyte‐based thermogenesis and energy balance regulation.
Low Maternal Dietary Intake of Choline Regulates Toll‐Like Receptor 4 Expression Via Histone H3K27me3 in Fetal Mouse Neural Progenitor Cells
Authors: Guan Xingying , Chen Xuedan , Dai Limeng , Ma Jiming , Zhang Qiming , Qu Song , Bai Yun , Wang Yanyan
Published: December 2020

Scope

Choline is an essential nutrient and a primary dietary source of methyl groups that are vital for brain development. Low choline (LC) in the maternal diet during pregnancy alters neurogenesis in the fetal brain and leads to low cognitive performance. However, the key signaling pathways that are sensitive to maternal choline supply during neural progenitor cell (NPC) development and the epigenetic mechanisms by which choline availability regulates gene expression are unclear.

Methods and results

Timed‐pregnant Nestin‐CFPnuc transgenic mice are fed either a control diet or LC diet during E11–17. Gene expression changes in sorted E17 NPCs are identified by RNA sequencing. A maternal LC diet significantly increases Tlr4 transcription, causing premature neuronal differentiation and enhanced ethanol‐induced NLRP3 inflammasome activation. No changes in DNA methylation at the Tlr4 gene promoter region are detected; however, a 70% decrease in H3K27me3 is observed in the LC‐treated NPCs. Inhibition of EZH2 decreases H3K27me3 levels and increases Tlr4 expression. Conversely, the application of catalytically inactive Cas9 with EZH2 to increase H3K27me3 at the Tlr4 promoter causes reduced Tlr4 expression.

Conclusion

These data reveal an epigenetic mechanism for the effect of maternal choline availability on brain development, suggesting a likely intervention for neurodevelopmental diseases.
The Garlic Compound Z‐Ajoene, S‐Thiolates COX2 and STAT3 and Dampens the Inflammatory Response in RAW264.7 Macrophages
Authors: Hitchcock Jessica K. , Mkwanazi Nonkululeko , Barnett Christopher , Graham Lisa M. , Katz Arieh A. , Hunter Roger , Schäfer Georgia , Kaschula Catherine H.
Published: December 2020

Scope

Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent to control inflammation‐associated pathologies. To investigate the underlying mechanisms, an in vitro inflammatory model is established using RAW264.7 murine macrophages exposed to low‐doses of lipopolysaccharide (LPS) in the presence of garlic compounds allicin and Z‐ajoene (ZA), mimicking regular garlic consumption.

Methods and Results

Both allicin and Z‐ajoene dampen both transcript and protein expression of the pro‐inflammatory cytokines IL1β, IL6, and IL12β, and upregulate the expression of the anti‐inflammatory cytokine IL10. Protein arrays of selected secreted inflammatory mediators confirm that Z‐ajoene has a pronounced down‐regulatory effect on LPS‐induced inflammatory cytokines and chemokines. Many of these proteins are known targets of the transcription factor signal transducer and activator of transcription 3 (STAT3); and indeed, Z‐ajoene or its analogue dansyl‐ajoene is found to decrease phosphorylation and nuclear translocation of STAT3, and to covalently modify the protein by S‐thiolation at Cys108, Cys367, and Cys687. Z‐Ajoene dose‐dependently and non‐competitively inhibit the activity of cyclooxygenase 2 (COX2), possibly attributed to S‐thiolation at Cys9 and Cys299.

Conclusion

The characterization of Z‐ajoene's activity of targeting and covalently modifying STAT3 and COX2, both important regulators of inflammation, may contribute to the health benefits of regular dietary garlic consumption.
An investigation of glutamate quantification with PRESS and MEGA‐PRESS
Authors: Cheng Hu , Wang Amanda , Newman Sharlene , Dydak Ulrike
Published: December 2020

Glutamate is an important neurotransmitter. Although many studies have measured glutamate concentration in vivo using magnetic resonance spectroscopy (MRS), researchers have not reached a consensus on the accuracy of glutamate quantification at the field strength of 3 T. Besides, there is not an optimal MRS protocol for glutamate measurement. In this work, both simulation and phantom scans indicate that glutamate can be estimated with reasonable accuracy (<10% error on average) using the standard Point‐RESolved Spectroscopy (PRESS) technique with TE 30 ms; glutamine, however, is likely underestimated, which is also suggested by results from human scans using the same protocol. The phantom results show an underestimation of glutamate and glutamine for PRESS with long TE and MEGA‐PRESS off‐resonance spectra. Despite the underestimation, there is a high correlation between the measured values and the true values (r > 0.8). Our results suggest that the quantification of glutamate and glutamine is reliable but can be off by a scaling factor, depending on the imaging technique. The outputs from all three PRESS sequences (TE = 30, 68 and 80 ms) are also highly correlated with each other (r > 0.7) and moderately correlated (r > 0.5) with the results from the MEGA‐PRESS difference spectra with moderate to good shimming (linewidth < 16 Hz).
Nursing students' willingness to work in geriatric care: An integrative review
Authors: Dai Fengling , Liu Yao , Ju Mei , Yang Yufeng
Published: December 2020

Aims

This integrative review aims to explore the willingness of nursing students to work in geriatric care over the past 10 years and to explore the factors influencing nursing students to work in geriatric care.

Design

An integrative review.

Methods

Studies investigating nursing students’ willingness in gerontological nursing work and related influencing factors published in English in Cochrane Library, MEDLINE, Embase, PsycINFO and CINAHL between 2010–2020 were included. Data collected in April 2020.

Results

Twenty‐four studies were analysed. Most studies presented a contradictory or negative attitude about the willingness of nursing students to engage in gerontological nursing work. In most studies that rank the intention to work in nursing fields, gerontological care received the lowest or a relatively low ranking. The main factors affecting work related to gerontological nursing include prior experience caring for older adults, attitudes towards geriatrics, anxiety about ageing, clinical practice environment and living experience with older family members.
Decreased nesting behavior, selective increases in locomotor activity in a novel environment, and paradoxically increased open arm exploration in Neurogranin knockout mice
Authors: Nakajima Ryuichi , Hattori Satoko , Funasaka Teppei , Huang Freesia L. , Miyakawa Tsuyoshi
Published: December 2020

Aims

Neurogranin (NRGN) is a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. Recent studies suggest that NRGN is involved in neuropsychiatric disorders, including schizophrenia, ADHD, and Alzheimer's disease. Previous behavioral studies of Nrgn knockout (Nrgn KO) mice identified hyperactivity, deficits in spatial learning, impaired sociability, and decreased prepulse inhibition, which suggest that these mice recapitulate some symptoms of neuropsychiatric disorders. To further validate Nrgn KO mice as a model of neuropsychiatric disorders, we assessed multiple domains of behavioral phenotypes in Nrgn KO mice using a comprehensive behavioral test battery including tests of homecage locomotor activity and nesting behavior.

Methods

Adult Nrgn KO mice (28‐54 weeks old) were subjected to a battery of comprehensive behavioral tests, which examined general health, nesting behavior, neurological characteristics, motor function, pain sensitivity, locomotor activity, anxiety‐like behavior, social behavior, sensorimotor gating, depression‐like behavior, and working memory.

Results

The Nrgn KO mice displayed a pronounced decrease in nesting behavior, impaired motor function, and elevated pain sensitivity. While the Nrgn KO mice showed increased locomotor activity in the open field test, these mice did not show hyperactivity in a familiar environment as measured in the homecage locomotor activity test. The Nrgn KO mice exhibited a decreased number of transitions in the light‐dark transition test and decreased stay time in the center of the open field test, which is consistent with previous reports of increased anxiety‐like behavior. Interestingly, however, these mice stayed on open arms significantly longer than wild‐type mice in the elevated plus maze. Consistent with previous studies, the mutant mice exhibited decreased prepulse inhibition, impaired working memory, and decreased sociability.

Conclusions

In the current study, we identified behavioral phenotypes of Nrgn KO mice that mimic some of the typical symptoms of neuropsychiatric diseases, including impaired executive function, motor dysfunction, and altered anxiety. Most behavioral phenotypes that had been previously identified, such as hyperlocomotor activity, impaired sociability, tendency for working memory deficiency, and altered sensorimotor gating, were reproduced in the present study. Collectively, the behavioral phenotypes of Nrgn KO mice detected in the present study indicate that Nrgn KO mice are a valuable animal model that recapitulates a variety of symptoms of neuropsychiatric disorders, such as schizophrenia, ADHD, and Alzheimer's disease.
Airborne geophysical data levelling based on variational mode decomposition
Authors: Zhang Qiong , Yan Fei , Liu Yunqing
Published: December 2020

A new technique is proposed to level airborne geophysical data based on the assumption that the level errors along the flight‐line direction have a distinguishable centre frequency. In the levelling method, airborne geophysical data from the entire survey area are corrected automatically after sorting the data into a group according to the measurement order. Variational mode decomposition is applied to the profile data to adaptively extract the level‐error component with distinct spectral bands. In airborne geophysical surveys, data in the anomalous region show visible peaks with strong gradients along the flight‐line direction, which would impact the decomposition. To minimize their effect on variational mode decomposition, the higher amplitude anomalies are grouped and discarded by K‐means clustering to obtain the real data level. The levelling method extracts the level errors of the entire survey area simultaneously, thus avoiding the regional error caused by strong noise, missing data or error transfer in the common levelling process. Moreover, the approach is automatic and applicable to both irregular and regular line patterns without the participation of staff members or tie‐line control. The levelling method may require much time when decomposition is performed on the extended survey area. We have applied the method to the airborne electromagnetic and magnetic data acquired by Geotech Limited to confirm its validity and have compared the obtained results with those based on the flight‐line correlation levelling algorithm.
‐Finite‐time stabilization of continuous‐time systems with optimal performance
Authors: Jin Nana , Xu Juanjuan , Zhang Huanshui
Published: December 2020

In this article, we are concerned with the ‐finite‐time stabilization (‐FTS) with optimal performance for the continuous‐time system. The definition of ‐FTS is first proposed. The main contribution is to give the equivalent conditions for the open‐loop solvability and sufficient conditions for the closed‐loop solvability of the ‐FTS problem with optimal performance for the finite‐time interval. Moreover, we show that the irregular optimal control problem is solvable under the ‐FTS of a specific system.
Treatment of Cancer-Associated Venous Thromboembolism with Low-Molecular-Weight Heparin or Direct Oral Anticoagulants: Patient Selection, Controversies, and Caveats
Authors: O'Connell Casey , Escalante Carmen P. , Goldhaber Samuel Z. , McBane Robert , Connors Jean M. , Raskob Gary E.
Published: December 2020

The treatment of venous thromboembolism (VTE) in patients with cancer is challenging because these patients have increased risks of both recurrent VTE and major bleeding, along with patient-specific and cancer-related factors that influence the approach to treatment. Historically, anticoagulant therapy with low-molecular-weight heparin (LMWH), given for both initial and long-term treatment, has been the preferred approach recommended by practice guidelines. Most recently, the National Comprehensive Cancer Network (NCCN) guidelines indicate that the direct oral anticoagulants (DOACs) apixaban, edoxaban, or rivaroxaban are preferred for patients without gastric or gastroesophageal lesions. DOACs have been associated with an increased risk of major bleeding in patients with gastrointestinal and possibly genitourinary cancers, and DOACs should either not be used (especially in those with intact intraluminal tumors) or be used with caution in patients with these cancers. Fatal or life-threatening bleeding occurs with similar frequency with DOACs or LMWH, and most major bleeding with DOACs can be managed with transfusion and standard measures. The patient's willingness and ability to comply with LMWH injections, and their treatment preference, should also be considered. Patients with cancer who have VTE should be treated with anticoagulation for a minimum of 6 months. Anticoagulation should be continued indefinitely while cancer is active or under treatment or if there are persistent risk factors for recurrent VTE. This article summarizes the evidence from clinical trials of LMWH and DOACs that underpins the NCCN guideline recommendations, addresses several controversies and caveats regarding anticoagulant treatment, and offers evidence-based, practical suggestions on patient selection for treatment with DOACs.

Implications for Practice

Several randomized trials support the addition of direct oral anticoagulants (DOACs) to the therapeutic armamentarium for cancer-associated venous thromboembolism (VTE). These agents come with unique risks and patient- and cancer-specific variables that must be evaluated during the course of a patient's cancer care. This narrative review discusses findings from clinical trials of low-molecular-weight heparin and DOACs for the treatment of cancer-associated VTE, evidence that supports the recent National Comprehensive Cancer Network guideline recommendations. A personalized approach to treatment is proposed that addresses patient selection for treatment with DOACs, factors that influence efficacy and safety, controversies and caveats, and suggestions for their resolution in clinical practice.
Tumor Response and Symptom Palliation from RAINBOW, a Phase III Trial of Ramucirumab Plus Paclitaxel in Previously Treated Advanced Gastric Cancer
Authors: Cascinu Stefano , Bodoky György , Muro Kei , Van Cutsem Eric , Oh Sang Cheul , Folprecht Gunnar , Ananda Sumitra , Girotto Gustavo , Wainberg Zev A. , Miron Maria Luisa Limon , Ajani Jaffer , Wei Ran , Liepa Astra M. , Carlesi Roberto , Emig Michael , Ohtsu Atsushi
Published: December 2020

Background

In the intent-to-treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation.

Materials and Methods

Tumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR.

Results

In both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation.

Conclusion

Treatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. NCT01170663.

Implications for Practice

Ramucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first-line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits.
Kinetic Target‐Guided Synthesis of Small‐Molecule G‐Quadruplex Stabilizers
Authors: Pomeislová Alice , Vrzal Lukáš , Kozák Jaroslav , Dobiaš Juraj , Hubálek Martin , Dvořáková Hana , Reyes‐Gutiérrez Paul E. , Teplý Filip , Veverka Václav
Published: December 2020

The formation of a G‐quadruplex motif in the promoter region of the c‐MYC protooncogene prevents its expression. Accordingly, G‐quadruplex stabilization by a suitable ligand may be a viable approach for anticancer therapy. In our study, we used the 4‐(4‐methylpiperazin‐1‐yl)aniline molecule, previously identified as a fragment library screen hit, as a template for the SAR‐guided design of a new small library of clickable fragments and subjected them to click reactions, including kinetic target‐guided synthesis in the presence of a G‐quadruplex forming oligonucleotide Pu24. We tested the clickable fragments and products of click reactions for their G‐quadruplex stabilizing activity and determined their mode of binding to the c‐MYC G‐quadruplex by NMR spectroscopy. The enhanced stabilizing potency of click products in biology assays (FRET, Polymerase extension assay) matched the increased yields of in situ click reactions. In conclusion, we identified the newly synthesized click products of bis‐amino derivatives of 4‐(4‐methylpiperazin‐1‐yl)aniline as potent stabilizers of c‐MYC G‐quadruplex, and their further evolution may lead to the development of an efficient tool for cancer treatment.
What Can a Water System Do to Prepare for a Power Outage?
Authors: Heaney Yvonne , Wollbrinck Jim , Macler Bruce A.
Published: December 2020

As wildfires and other extreme weather events take their toll on water system security, including a Public Safety Power Shutoff program as part of an emergency response plan can keep your system running when it counts the most.
Synthesis and properties of self‐healing cross‐linked nonisocyanate polyurethanes from biobased diglycerol bis(cyclic carbonate)
Authors: Wang Ding‐wen , Chen Shuo , Zhao Jing‐bo , Zhang Zhi‐yuan , Zhang Jun‐ying
Published: December 2020

A simple and green method was established to prepare self‐healing cross‐linked nonisocyanate polyurethanes (SH‐cNIPUs) from biobased diglycerol bis(cyclic carbonate) (DGDC). Two nonisocyanate polyurethane prepolymers with furan terminal groups (tFU‐NIPUs) were synthesized through a ring‐opening reaction of DGDC with furan methylamine and trimethylolpropane tris(poly[propylene glycol], amine terminated) ether, or tris(2‐aminoethyl) amine under mild conditions. The SH‐cNIPUs were prepared via a Diels–Alder reaction between tFU‐NIPUs and a bismaleimide. SH‐cNIPUs were characterized by ATI‐FTIR,1H NMR, differential scanning calorimetry, polarized optical microscope, and tensile strength after being damaged and healed. SH‐cNIPUs with glass transition temperature from 8 to 49°C, tensile strength up to 21 MPa, and self‐healing efficiency from 67 to 80% were successfully synthesized.