bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abandoning statistical significance is both sensible and practical
Authors: Amrhein Valentin , Gelman Andrew , Greenland Sander , McShane Blakeley B 
Published: April 2019

To the Editor of JAMA

Dr Ioannidis writes against our proposals to abandon statistical significance in scientific reasoning and publication, as endorsed in the editorial of a recent special issue of an American Statistical Association journal devoted to moving to a “post p<0.05 world.” We appreciate that he echoes our calls for “embracing uncertainty, avoiding hyped claims…and recognizing ‘statistical significance’ is often poorly understood.” We also welcome his agreement that the “interpretation of any result is far more complicated than just significance testing” and that “clinical, monetary, and other considerations may often have more importance than statistical findings.”
Nonetheless, we disagree that a statistical significance-based “filtering process is useful to avoid drowning in noise” in science and instead view such filtering as harmful. First, the implicit rule to not publish nonsignificant results biases the literature with overestimated effect sizes and encourages “hacking” to get significance. Second, nonsignificant results are often wrongly treated as zero. Third, significant results are often wrongly treated as truth rather than as the noisy estimates they are, thereby creating unrealistic expectations of replicability. Fourth, filtering on statistical significance provides no guarantee against noise. Instead, it amplifies noise because the quantity on which the filtering is based (the p-value) is itself extremely noisy and is made more so by dichotomizing it.
We also disagree that abandoning statistical significance will reduce science to “a state of statistical anarchy.” Indeed, the journal Epidemiology banned statistical significance in 1990 and is today recognized as a leader in the field.
Valid synthesis requires accounting for all relevant evidence—not just the subset that attained statistical significance. Thus, researchers should report more, not less, providing estimates and uncertainty statements for all quantities, justifying any exceptions, and considering ways the results are wrong. Publication criteria should be based on evaluating study design, data quality, and scientific content—not statistical significance.
Decisions are seldom necessary in scientific reporting. However, when they are required (as in clinical practice), they should be made based on the costs, benefits, and likelihoods of all possible outcomes, not via arbitrary cutoffs applied to statistical summaries such as p-values which capture little of this picture.
The replication crisis in science is not the product of the publication of unreliable findings. The publication of unreliable findings is unavoidable: as the saying goes, if we knew what we were doing, it would not be called research. Rather, the replication crisis has arisen because unreliable findings are presented as reliable.
Cloning and characterization of a tyrosine decarboxylase involved in the biosynthesis of galanthamine inLycoris aurea
Authors: Wang Rong , Han Xiaokang , Xu Sheng , Xia Bing , Jiang Yumei , Xue Yong , Wang Ren 
Published: April 2019

BackgroundGalanthamine, one kind of Amaryllidaceae alkaloid extracted from theLycorisspecies, is used in the treatment of Alzheimer’s disease. In regards to medical and economic importance, the biosynthesis and regulatory mechanism of the secondary metabolites inLycorisremain uninvestigated.MethodsBLAST was used to identify the sequence of tyrosine decarboxylase in the transcriptome ofLycoris aurea(L’Hér) Herb. The enzyme activity of this TYDC was determined by using heterologous expressed protein in theEscherichia colicells. The related productive contents of tyramine were detected using High Performance Liquid Chromatography (HPLC). According to the available micro RNA sequencing profiles and degradome database ofL. aurea, microRNA396 were isolated, which targets toLaTYDC1and RNA Ligase-Mediated-Rapid Amplification of cDNA Ends (RLM-RACE) were used to confirm the cleavage. The expression levels of miR396 andLaTYDC1were measured using a quantitative real-time polymerase chain reaction (qRT-PCR).ResultsLaTYDC1 was mainly expressed in root, bulb, leaf and flower fitting the models for galanthamine accumulation. This decarboxylase efficiently catalyzes tyrosine to tyramine conversion. Under methyl jasmonate (MeJA) treatment, the expression ofLaTYDC1and the content of tyramine sharply increase. The use of RLM-RACE confirms that miR396 promotes the degradation ofLaTYDC1mRNA. Under MeJA treatment, the expression of miR396 was suppressed while the expression level ofLaTYDC1sharply increased. Following the increase of the miR396 transcriptional level,LaTYDC1was significantly repressed.ConclusionLaTYDC1 participates in the biosynthesis of galanthamine, and is regulated by miR396. This finding also provides genetic strategy for improving the yield of galanthamine in the future.
Identification and expression analysis of the GDSL esterase/lipase family genes, and the characterization of SaGLIP8 in Sedum alfredii Hance under cadmium stress
Authors: Li He , Han Xiaojiao , Qiu Wenmin , Xu Dong , Wang Ying , Yu Miao , Hu Xianqi , Zhuo Renying 
Published: April 2019

Background
The herb Sedum alfredii (S. alfredii) Hance is a hyperaccumulator of heavy metals (cadmium (Cd), zinc (Zn) and lead (Pb)); therefore, it could be a candidate plant for efficient phytoremediation. The GDSL esterase/lipase protein (GELP) family plays important roles in plant defense and growth. Although the GELP family members in a variety of plants have been cloned and analyzed, there are limited studies on the family’s responses to heavy metal-stress conditions.

Methods
Multiple sequence alignments and phylogenetic analyses were performed according to the criteria described. A WGCNA was used to construct co-expression regulatory networks. The roots of S. alfredii seedlings were treated with 100 µM CdCl2 for qRT-PCR to analyze expression levels in different tissues. SaGLIP8 was transformed into the Cd sensitive mutant strain yeast Δycf1 to investigate its role in resistance and accumulation to Cd.

Results
We analyzed GELP family members from genomic data of S. alfredii. A phylogenetic tree divided the 80 identified family members into three clades. The promoters of the 80 genes contained certain elements related to abiotic stress, such as TC-rich repeats (defense and stress responsiveness), heat shock elements (heat stress) and MYB-binding sites (drought-inducibility). In addition, 66 members had tissue-specific expression patterns and significant responses to Cd stress. In total, 13 hub genes were obtained, based on an existing S. alfredii transcriptome database, that control 459 edge genes, which were classified into five classes of functions in a co-expression subnetwork: cell wall and defense function, lipid and esterase, stress and tolerance, transport and transcription factor activity. Among the hub genes, Sa13F.102 (SaGLIP8), with a high expression level in all tissues, could increase Cd tolerance and accumulation in yeast when overexpressed.

Conclusion
Based on genomic data of S. alfredii, we conducted phylogenetic analyses, as well as conserved domain, motif and expression profiling of the GELP family under Cd-stress conditions. SaGLIP8 could increase Cd tolerance and accumulation in yeast. These results indicated the roles of GELPs in plant responses to heavy metal exposure and provides a theoretical basis for further studies of the SaGELP family’s functions.
Capping Silica Nanoparticles with Tryptophan‐Mediated Cucurbit[8]uril Complex for Targeted Intracellular Drug Delivery Triggered by Tumor‐Overexpressed IDO1 Enzyme
Authors: Qiao Haishi , Jia Jing , Shen Haowen , Zhao Sibo , Chen Enping , Chen Wei , Di Bin , Hu Chi 
Published: April 2019

AbstractNanosystems responsive to tumor‐specific enzymes are considered as a highly attractive approach to intracellular drug release for targeted cancer therapy. Mesoporous silica nanoparticles are capped with tryptophan‐mediated cucurbit[8]uril complex with Fe3O4 to minimize the premature drug leakage while being able to deliver the payload on demand at the target tissue. The supramolecular interaction between tryptophan and cucurbit[8]uril is disrupted in the presence of indoleamine 2,3‐dioxygenase 1 (IDO1) enzyme (abundant in the tumor intracellular microenvironment), which catalyzes the metabolism of tryptophan into N‐formylkynurenine, resulting in the disassembly of the “gate‐keeper” of the nanocarriers and intracellular release of therapeutics exclusively in tumor cells. The drug release from the nanocarrier with high selectivity to overexpressed IDO1 enzyme induces significant cytotoxicity against HepG2 cells in vitro, as well as the superior antitumor effects in vivo. This robust supramolecular nanosystem with sophisticated structure and property provides a promising platform for intracellular drug release targeting the intrinsic microenvironmental enzyme inside the tumor cells.
Effect of Electric Field on the Lubricating Performance of Ga‐Based Liquid Metal
Authors: Guo Jie , Cheng Jun , Tan Hui , Zhu Shengyu , Qiao Zhuhui , Yang Jun , Liu Weimin 
Published: April 2019

AbstractGa‐based liquid metal (GLM) can be used as a current‐carrying lubricant, due to its combination of excellent electrical conductivity and good lubricity. However, the influence of electric field parameters on the lubrication mechanism of GLM is still unclear. This paper attempts to investigate the influence of current magnitude, voltage magnitude, current direction, and load on the lubrication behaviors of GLM at atmosphere and room temperature (≈26 °C). It is found that the interface action mechanism induced by an electric field is mainly reflected in four aspects, namely, Joule heating effect, electric field force, electrochemical effect, and electromigration effect. These interfacial physical and chemical effects are governed by the current magnitude, voltage magnitude, current direction, and load, bringing about distinct frictional products and thereby influencing the lubrication behaviors. Briefly, FeGa3 can only be formed when the current reaches 6 A and the load is above 40 N, and it has obvious friction‐reducing properties, but increases the wear due to its low content. When the frictional product is just the Ga‐rich film, the increase of oxidation degree is detrimental to the wear resistance.
Generating Energy from Air: Solid State Planar Concentration Cell Based on Graphene Oxide
Authors: Wei Di 
Published: April 2019

AbstractAdv. Mater. Technol. 2016, 1, 1600145The above article from Advanced Materials Technologies, published online on 5 September 2016 and in Volume 1, Issue 8 in Wiley Online Library (http://onlinelibrary.wiley.com), has been retracted at the request of Nokia, and in agreement with the journal Editor‐in‐Chief and Wiley.Following an investigation conducted by Nokia, the retraction has been agreed because it was ascertained by Nokia that the author reported results which included other people's ideas and experiments without their knowledge and consent, that he did not acknowledge all those involved in the study, and that he submitted the manuscript to the journal without prior vetting and authorization by Nokia, in violation of Nokia's policies.[1] D. Wei, Adv. Mater. Technol. 2016, 1, 1600145, https://doi.org/10.1002/admt.201600145.
Synthesis of Benzo[a]quinolizidines via an Aza‐Michael/Oxidative Mannich Process
Authors: Jung Areum , Min Sun‐Joon 
Published: April 2019

AbstractThe synthesis of substituted benzo[a]quinolizidines via aza‐Michael addition of tetrahydroisoquinolines to alkyl vinyl ketones, followed by oxidative Mannich cyclization, is described. Various Michael adducts are easily prepared, and subsequent DDQ‐mediated oxidations stereoselectively afford the corresponding azacycles efficiently. Furthermore, the one‐pot aza‐Michael/oxidative Mannich process gave benzo[a]quinolizidines, thus providing a metal‐free and practical synthetic route to N‐heterocyclic building blocks.
Lipase‐Powered Mesoporous Silica Nanomotors for Triglyceride Degradation
Authors: Wang Lei , Hortelão Ana C. , Huang Xin , Sánchez Samuel 
Published: April 2019

AbstractWe report lipase‐based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets that mimic “blood lipids”. We achieved about 40 min of enhanced diffusion of lipase‐modified mesoporous silica nanoparticles (MSNPs) through a biocatalytic reaction between lipase and its corresponding water‐soluble oil substrate (triacetin) as fuel, which resulted in an enhanced diffusion coefficient (ca. 50 % increase) at low triacetin concentration (<10 mm). Lipase not only serves as the power engine but also as a highly efficient cleaner for the triglyceride droplets (e.g., tributyrin) in PBS solution, which could yield potential biomedical applications, for example, for dealing with diseases related to the accumulation of triglycerides, or for environmental remediation, for example, for the degradation of oil spills.
Geochemical Sources and Availability of Amidophosphates on the Early Earth
Authors: Gibard Clémentine , Gorrell Ian B. , Jiménez Eddy I. , Kee Terence P. , Pasek Matthew A. , Krishnamurthy Ramanarayanan 
Published: April 2019

AbstractPhosphorylation of (pre)biotically relevant molecules in aqueous medium has recently been demonstrated using water‐soluble diamidophosphate (DAP). Questions arise relating to the prebiotic availability of DAP and other amidophosphosphorus species on the early earth. Herein, we demonstrate that DAP and other amino‐derivatives of phosphates/phosphite are generated when Fe3P (proxy for mineral schreibersite), condensed phosphates, and reduced oxidation state phosphorus compounds, which could have been available on early earth, are exposed to aqueous ammonia solutions. DAP is shown to remain in aqueous solution under conditions where phosphate is precipitated out by divalent metals. These results show that nitrogenated analogues of phosphate and reduced phosphite species can be produced and remain in solution, overcoming the thermodynamic barrier for phosphorylation in water, increasing the possibility that abiotic phosphorylation reactions occurred in aqueous environments on early earth.
Facile Preparation of Spirolactones by an Alkoxycarbonyl Radical Cyclization–Cross‐Coupling Cascade
Authors: Weires Nicholas A. , Slutskyy Yuriy , Overman Larry E. 
Published: April 2019

AbstractAn alkoxycarbonyl radical cyclization–cross‐coupling cascade has been developed that allows functionalized γ‐butyrolactones to be prepared in one step from simple tertiary alcohol‐derived homoallylic oxalate precursors. The reaction succeeds with aryl and vinyl electrophiles and is compatible with heterocyclic fragments in both coupling partners. This chemistry allows for the rapid construction of spirolactones, which are of interest in drug discovery endeavors.
Synthesis, Properties, and Application of Tetrakis(pentafluoroethyl)gallate, [Ga(C2F5)4]−
Authors: Niemann Mark , Neumann Beate , Stammler Hans‐Georg , Hoge Berthold 
Published: April 2019

AbstractWeakly coordinating anions (WCAs) are important for academic reasons as well as for technical applications. Tetrakis(pentafluoroethyl)gallate, [Ga(C2F5)4]−, a new WCA, is accessible by treatment of [GaCl3(dmap)] (dmap=4‐dimethylaminopyridine) with LiC2F5. The anion [Ga(C2F5)4]− proved to be reluctant towards deterioration by aqueous hydrochloric acid or lithium hydroxide. Various salts of [Ga(C2F5)4]− were synthesized with cations such as [PPh4]+, [CPh3]+, [(O2H5)2(OH2)2]2+, and [Li(dec)2]+ (dec=diethyl carbonate). Thermolysis of [(O2H5)2(OH2)2][Ga(C2F5)4]2 gives rise to a dihydrate of tris(pentafluoroethyl)gallane, [Ga(C2F5)3(OH2)2]. All products were characterized by NMR and IR spectroscopy, mass spectrometry, X‐ray diffraction, and elemental analysis. Furthermore, an outlook for the application of [Li(dec)2][Ga(C2F5)4] as a conducting salt in lithium‐ion batteries is presented.
Anatomical Assessment of the Adult Skeleton of Zebrafish Reared Under Different Thyroid Hormone Profiles
Authors: Keer Stephanie , Cohen Karly , May Catherine , Hu Yinan , McMenamin Sarah , Hernandez Luz Patricia 
Published: April 2019

ABSTRACTThyroid hormone (TH) directs the growth and maintenance of tissues throughout the body during development and into adulthood, and plays a particularly important role in proper ossification and homeostasis of the skeleton. To better understand the roles of TH in the skeletogenesis of a vertebrate model, and to define areas of the skeleton that are particularly sensitive to developmental TH, we examined the effects of hypo‐ and hyperthyroidism on skeletal development in zebrafish. Performing a bone‐by‐bone anatomical assessment on the entire skeleton of adult fish, we found that TH is required for proper ossification, growth, morphogenesis, and fusion of numerous bones. We showed that the pectoral girdle, dermatocranium, Weberian apparatus, and dentary are particularly sensitive to TH, and that TH affects development of skeletal element regardless of bone type and developmental origin. Indeed, the hormone does not universally promote ossification: we found that developmental TH prevents ectopic ossification in multiple thin bones and within connective tissue of the jaw. In all, we found that TH regulates proper morphogenesis and ossification in the majority of zebrafish bones, and that the requirement for the hormone extends across bone types and developmental profiles. Anat Rec, 302:1754–1769, 2019. © 2019 American Association for Anatomy
Design, synthesis, in silico ADMET profile and GABA‐A docking of novel phthalazines as potent anticonvulsants
Authors: El‐Helby Abdel‐Ghany A. , Ayyad Rezk R. A. , Zayed Mohamed F. , Abulkhair Hamada S. , Elkady Hazem , El‐Adl Khaled 
Published: April 2019

AbstractA new series of 2‐substituted‐2,3‐dihydrophthalazine‐1,4‐diones (2‒9) were designed and synthesized to evaluate their anticonvulsant activity. The neurotoxicity was assessed using the rotarod test. Molecular docking was performed for the synthesized compounds to assess their binding affinities as γ‐aminobutyric acid A (GABA‐A) receptor agonists as a possible mechanism of their anticonvulsant action, to rationalize their anticonvulsant activity in a qualitative way. The data obtained from the molecular modeling was strongly matched with that obtained from the biological screening, which revealed that compounds5a,9b, and9hshowed the highest binding affinities toward the GABA‐A receptor and also showed the highest anticonvulsant activities with relative potencies of 1.66, 1.63, and 1.61, respectively, compared with diazepam. The most active compounds5a,9b, and9hwere further tested against maximal electroshock seizures. Compounds5aand9bshowed 100% protection at a dose level of 125 µg/kg, while compound9hexhibited 83.33% protection at the same dose level. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and to explain the possible mechanism for their anticonvulsant action. These agents exerted low neurotoxicity and a high safety margin compared with valproate as a reference drug. Most of our designed compounds exhibited a good ADMET profile.
Porphyrin‐containing Polyimide with Enhanced Light Absorption and Photocatalysis Activity
Authors: Cui Zhiwei , Zhou Jun , Liu Teng , Wang Yicong , Hu Yue , Wang Ying , Zou Zhigang 
Published: April 2019

AbstractA series of porphyrin‐containing polyimide (PI) photocatalysts were synthesized by a one‐step solvothermal method. Characterization results revealed that porphyrin was uniformly coupled into the PI framework through covalent bonding and the visible‐light absorption was greatly improved. The photodegradation activity of porphyrin‐containing PIs for methyl orange (MO) under visible light was enhanced significantly, with the highest pseudo‐first‐order rate constant 35 times higher than that of neat porphyrin and 10 times higher than that of porphyrin‐free PI. The enhancement is mainly attributed to an increased light harvesting accompanied by a varied HOMO level, which was clarified by control experiments, characterizations and theoretical calculations. This work provides an insight into multiple effects of dye molecules in dye‐containing heterogeneous photocatalysts.
Coexisting Cooperative Cognitive Micro‐/Nanorobots
Authors: Chang Xiaocong , Tang Wentian , Feng Yiwen , Yu Hao , Wu Zhiguang , Xu Tailin , Dong Huijuan , Li Tianlong 
Published: April 2019

AbstractInteraction behaviors are a crucial, distinctive feature of organisms in ecological systems. Inspired by nature, micro‐/nanorobots also show interaction behaviors with a significant number of novel and advanced functionalities. The micro‐/nanoscale size and self‐driven abilities of micro‐/nanorobots have attracted considerable attention for potential applications. The mission of micro‐/nanorobots has evolved from basic mechanical transfer or assistance to a diverse range of complex tasks, such as targeted drug delivery, biosensing, and environmental remediation. Herein, we focus on the interaction behavior of coexisting cooperative cognitive (Tri‐Co) micro‐/nanorobots, summarize recent research, and classify the interactions into three broad types: with the environment, with robot peers, and with human external control.
A case–control analysis of maternal diet and risk of neural tube defects in Bangladesh
Authors: Obrycki John F. , Lee Jane J. , Kapur Kush , Paul Ligi , Hasan Md Omar Sharif Ibne , Mia Selim , Quamruzzaman Quazi , Christiani David C. , Mazumdar Maitreyi 
Published: April 2019

AbstractObjectivesMothers need a nutrient‐rich diet for healthy neural tube development. Neural tube defect risk can be reduced through fortifying grain products with folic acid and taking folic acid supplements. Fortification is not required in Bangladesh. Maternal supplement use rates are low, similar to other countries. This study evaluates maternal dietary intake during pregnancy to identify possible interventions.MethodsA food frequency questionnaire (FFQ) assessed maternal diet. The primary aim compared dietary intake (calories, fat, carbohydrate, protein, fiber, vitamins, and minerals) between mothers of infants with myelomeningocele (cases) and mothers of controls. Secondary aims included (i) comparing foods consumed and (ii) evaluating if rice intake correlated with arsenic exposure. Pairedt‐tests, Wilcoxon signed rank tests, McNemar's chi‐squared test, and linear regression were used.ResultsThis study included 110 matched mother–infant pairs (55 cases/55 controls). Mothers of cases and mothers of controls had similar caloric intake [median 2406 kcal/day vs. 2196 kcal/day (p = 0.071)]. Mothers in both groups consumed less than half the daily recommended 600 μg of folate. Diets were potentially deficient in vitamins A, D, E, potassium, sodium, and iron. Steamed rice was the primary food consumed for both groups, and this rice intake was not associated with toenail arsenic.ConclusionsDietary interventions should increase folate, vitamins A, D, E, potassium, sodium, and iron intake in Bangladeshi mothers. Folic acid fortification of grain products maybe the only viable strategy to achieve adequate folate intake for mothers. Given the central role of rice to the Bangladeshi diet, fortifying rice may be a viable option.