bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and molecular characterization of patients with hereditary hemorrhagic telangiectasia: Experience from an HHT Center of Excellence
Authors: Latif Muhammad A. , Sobreira Nara Lygia D. , Guthrie Kelsey S. , Motaghi Mina , Robinson Gina M. , Shafaat Omid , Gong Anna J. , Weiss Clifford R. 
Published: March 2021

AbstractIn this retrospective single‐center study, we evaluated whether/how pathogenic/likely pathogenic variants of three hereditary hemorrhagic telangiectasia (HHT)–associated genes (ENG, ACVRL1, and SMAD4) are associated with specific clinical presentations of HHT. We also characterized the morphological features of pulmonary arteriovenous malformations (AVMs) in patients with these variants. Pathogenic or likely pathogenic variants were detected in 64 patients. Using nonparametric statistical tests, we compared the type and prevalence of specific HHT diagnostic features associated with these three variants. Pathogenic variants in these genes resulted in gene‐specific HHT clinical presentations. Epistaxis was present in 93%, 94%, and 100% of patients with ENG, ACVRL1, and SMAD4 variants, respectively (p = 0.79). Pulmonary AVMs were more common in patients with the ENG variant (p = 0.034) compared with other subgroups. ACVRL1 variant was associated with the lowest frequency of pulmonary AVMs (p = 0.034) but the highest frequency of hepatic AVMs (p = 0.015). Patients with the ACVRL1 variant did not have significantly more pancreatic AVMs compared with the other groups (p = 0.72). ENG, ACVRL1, and SMAD4 pathogenic or likely pathogenic variants are associated with gene‐specific HHT presentations, which is consistent with results from other HHT centers.
Stereoselective Directed Cationic Cascades Enabled by Molecular Anchoring in Terpene Cyclases
Authors: Schneider Andreas , Jegl Philipp , Hauer Bernhard 
Published: March 2021

AbstractCascade reactions appeared as a cutting‐edge strategy to streamline the assembly of complex structural scaffolds from naturally available precursors in an atom‐, as well as time, labor‐ and cost‐efficient way. We herein report a strategy to control cationic cyclization cascades by exploiting the ability of anchoring dynamic substrates in the active site of terpene cyclases via designed hydrogen bonding. Thereby, it is possible to induce “directed” cyclizations in contrast to established “non‐stop” cyclizations (99:1) and predestinate cascade termination at otherwise catalytically barely accessible intermediates. As a result, we are able to provide efficient access to naturally widely occurring apocarotenoids, value‐added flavors and fragrances in gram‐scale by replacing multi‐stage synthetic routes to a single step with unprecedented selectivity (>99.5 % ee) and high yields (up to 89 %).
Study on polyurethane‐acrylate/cerium dioxide modified by 3‐(Methylacryloxyl)propyltrimethoxy silane and its UV absorption property
Authors: Yu Xiaochen , Zheng Jia , Zhou Zhaoxi , Chen Qihui , Hong Maochun , Fu Heqing 
Published: March 2021

AbstractFirstly, cerium dioxide(CeO2) was modified by 3‐(Methylacryloxyl)propyltrimethoxy silane (KH‐570), and modified CeO2 (mCeO2) was prepared. Then poly (urethane‐acrylate) was modified by mCeO2, and poly (urethane‐acrylate)/modified CeO2 (PUA/mCeO2) composites with ultraviolet absorption property were prepared. The morphology, thermal hydrophobicity, mechanical properties, optical properties, and UV‐absorption properties of PUA/mCeO2 composites were studied. XRD and SEM analysis showed that the modified CeO2 had better dispersion in the matrix than that of pure CeO2. Ultraviolet–visible spectrum and thermogravimetric analysis were used to characterize the optical properties and thermal stability of PUA/mCeO2 composites. The results showed that with the increasing of the mCeO2 content, the UV‐absorption property of PUA/mCeO2 composites was improved gradually. When the content of mCeO2 is 3%, the absorption of ultraviolet of PUA/mCeO2 composites is about 5 times of pure PUA film, and the absorption band is mainly in the UVA section. The thermal stability of PUA/mCeO2 composites was improved with the adding of mCeO2. With the increasing of mCeO2 content, the contact angle of PUA/mCeO2 composites increased significantly. And the UV‐absorption mechanism of PUA/mCeO2 Composites was studied. UV‐curable PUA/mCeO2 composites have good UV absorption property and water resistance. They will be used in the sun screen and protect people's skin.
Anthropogenic influence on the intensity of extreme precipitation in the Asian‐Australian monsoon region in HadGEM3‐A‐N216
Authors: Liu Jieyu , Qiao Shaobo , Li Chao , Tang Shankai , Chen Dong , Feng Guolin 
Published: March 2021

AbstractThe Asian‐Australian monsoon (AAM) region is characterized as abundant summer monsoon rainfall, which provides fresh water resources for high‐density population there. The research uses HadGEM3‐A‐N216 model simulations to compare the change of extreme rainfall intensity in the AAM region with and without anthropogenic influences. Although the anthropogenic forcing exerts a weak impact on the climatological mean distribution of the extreme precipitation, it significantly increases the extreme precipitation intensity at each degree in most parts of the AAM region, especially for the northern East Asia, the Bay of Bengal, and Australia. As the extreme degree increases from the 50–98%, the extreme precipitation intensity in the northern East Asia, the Bay of Bengal, and the Australia increase more and more rapidly, while that in the southern East Asia changes from a decreasing trend to an increasing trend. Overall, the stronger extreme precipitation is accompanied by a stronger growth trend under the anthropogenic forcing.
Autocorrelation and estimates of treatment effect size for single‐case experimental design data
Authors: Barnard‐Brak Lucy , Watkins Laci , Richman David M. 
Published: March 2021

AbstractWe examined the degree of autocorrelation among single‐case design data with six measures used to estimate treatment effect size. The most commonly used measures of effect size for single‐case data over the last 5 years published in peer‐reviewed journals were selected for comparison. The overall mean degree of autocorrelation was 0.46 (SD = 0.33) across the 304 data paths, which represents a moderate degree of autocorrelation. Overall, it appears that non‐parametric measures of effect size (i.e., percent of non‐overlapping data [PND], non‐overlap of all pairs [NAP], and improvement rate difference [IRD] values) were substantially and significantly more influenced by the degree of autocorrelation. Tau‐U effect size estimate was the non‐parametric exception as it was not significantly influenced by the degree of autocorrelation. Parametric measures of effect sizes such as standardized mean difference (SMD) and log response ratio (LRR) values did not appear to be significantly influenced by the degree of autocorrelation. For SMD, LRR, and Tau‐U values, the correlation between the effect size value and the degree of autocorrelation was minimal. For NAP, IRD, and PND values, the correlation between the effect size value and the degree of autocorrelation was moderate, indicating that these estimates of effect size should be avoided as the degree of autocorrelation between data points increases.
Cerebral glucose metabolism in bipolar disorder: A voxel‐based meta‐analysis of positron emission tomography studies
Authors: Wu Chujun , Ren Chutong , Teng Ziwei , Li Sujuan , Silva Floyd , Wu Haishan , Chen Jindong 
Published: March 2021

AbstractBackgroundPrevious positron emission tomography studies have reported the changes of cerebral glucose metabolism in bipolar disorder. However, the findings across studies remain controversial, containing differing results.MethodsA systematic literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted. We conducted a voxel‐wide meta‐analysis of cerebral glucose metabolism studies, using the seed‐based mapping approach, in patients with bipolar disorder (BD).ResultsWe identified 7 studies suitable for inclusion, which included a total of 126 individuals with BD and 160 healthy controls. The most consistent and robust findings were an increase in cerebral glucose metabolism in the right precentral gyrus and a decrease in the left superior temporal gyrus, left middle temporal gyrus, and cerebellum. Additionally, the sex distribution and illness duration had significant moderating effects on cerebral glucose metabolism alterations.ConclusionsCerebral glucose metabolism alterations in these brain regions are likely to reflect the disease‐related functional abnormalities such as emotion and cognition. These findings contribute to a better understanding of the neurobiological underpinnings of bipolar disorder.Limitations.This study was done at a study level and cannot be addressed at the patient level. Subgroup analysis of BD I and BD II is not possible due to limited literature data.
Hyperandrogenism, oligomenorrhea, and erythrocytosis caused by an ovarian Leydig cell tumor: A case report
Authors: Mendonça Fernando , Souto Selma , Magalhães Daniela , Portugal Raquel , Coelho Ana Rita , Fernandes Ana Sofia , Falcão Vera , Tavares Sara , Portugal Inês , Beires Jorge , Carvalho Davide 
Published: March 2021

AbstractLeydig cell tumors are rare ovarian neoplasms. Affected individuals typically present with amenorrhea/oligomenorrhea and rapidly progressive features of virilization. Erythrocytosis can also occur as a result of high testosterone levels.
Circularly Polarized Fluorescent Helicene‐Boranils: Synthesis, Photophysical and Chiroptical Properties
Authors: Macé Aurélie , Hamrouni Khaoula , Gauthier Etienne S. , Jean Marion , Vanthuyne Nicolas , Frédéric Lucas , Pieters Grégory , Caytan Elsa , Roisnel Thierry , Aloui Faouzi , Srebro‐Hooper Monika , Carboni Bertrand , Berrée Fabienne , Crassous Jeanne 
Published: March 2021

AbstractMono‐ and di‐boranil‐substituted helicenes were prepared by BF2‐borylation of the corresponding anils, readily synthesized by condensation of 2‐amino‐ and 2,15‐diamino‐helicenes with 4‐(diethylamino)salicylaldehyde. After enantiomeric resolution using HPLC, their chiroptical properties including circularly polarized fluorescence in solution and in PMMA films were investigated and rationalized with the help of NMR, X‐ray and quantum‐chemical calculations.
Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
Authors: Cabrero Cristina , Martín‐Pintado Nerea , Mazzini Stefania , Gargallo Raimundo , Eritja Ramon , Aviñó Anna , González Carlos 
Published: March 2021

AbstractWe report the structural effect of 2'‐deoxy‐2',2'‐difluorocytidine (dFdC) insertions in the DNA strand of a DNA : RNA hybrid duplex and in a self‐complementary DNA : DNA duplex. In both cases, the modification slightly destabilizes the duplex and provokes minor local distortions that are more pronounced in the case of the DNA : RNA hybrid. Analysis of the solution structures determined by NMR methods show that dFdC is an adaptable derivative that adopts North type sugar conformation when inserted in pure DNA, or a South sugar conformation in the context of DNA : RNA hybrids. In this latter context, South sugar pucker favors the formation of a 2'F⋅⋅H8 attractive interaction with a neighboring purine, which compensates the destabilizing effect of base pair distortions. These interactions share some features with pseudohydrogen bonds described previously in other nucleic acids structures with fluorine modified sugars.
Transition‐Metal‐Free α Csp3−H Cyanation of Sulfonamides
Authors: Zhou Liejin , Wei Siqi , Lei Ziran , Zhu Gangguo , Zhang Zuxiao 
Published: March 2021

AbstractThis report describes the site‐selective α‐functionalization of sulfonylamide derivatives through the in‐situ generation of imine intermediates. The N−F sulfonylamides, which could facilitate the elimination to generate imines, are coupled with TBACN to efficiently and mildly afford α‐amino cyanides. Comparing with Strecker reaction, this transformation offers a complementary strategy to efficiently construct α‐amino cyanides from direct α C−H functionalization of sulfonylamindes. The reaction is also characterized by broad substrate scope and flash chromatography column free workup. More importantly, the new two‐electron pathway to generate imines through manipulation of the leaving group allows us to achieve excellent α site‐selectivity.
[As3M(As3Pb3)]3− (M = Nb, Ta): Ternary Heterometallic Clusters with Early Transition Metal Atoms and Aromatic [Pb3]2−
Authors: Shu Cong‐Cong , Qiao Lei , Muñoz‐Castro Alvaro , Sun Zhong‐Ming 
Published: March 2021

Main observation and conclusionTwo ternary clusters, [As3Nb(As3Pb3)]3− 1 and [As3Ta(As3Pb3)]3− 2, were directly extracted from “K8NbPbAs5” and “K8TaPbAs5” intermetallic solid in the presence of ethylenediamine and 2.2.2‐crypt, respectively. Both 1 and 2, comprising an electron‐poor early transition metal‐atom Nb or Ta coordinated to a As3 triangle and a bowl‐like As3Pb3, were characterized by single crystal X‐ray diffraction, energy dispersive X‐ray (EDX) and electrospray ionization mass‐spectrometry (ESI‐MS). They also represent the first examples of the Pb‐As hybrid in solution‐based Zintl anion chemistry and DFT calculations revealed a σ‐aromaticity of the [Pb3]2− unit.
Identification of NTRK gene fusions in lung adenocarcinomas in the Chinese population
Authors: Zhao Ruiying , Yao Feng , Xiang Chan , Zhao Jikai , Shang Zhanxian , Guo Lianying , Ding Wenjie , Ma Shengji , Yu Anbo , Shao Jinchen , Zhu Lei , Han Yuchen 
Published: March 2021

AbstractThe molecular profile of neurotrophic tyrosine kinase receptor (NTRK) gene fusions in lung adenocarcinoma (LUAD) is not fully understood. Next‐generation sequencing (NGS) and pan‐tyrosine kinase receptor (TRK) immunohistochemistry (IHC) are powerful tools for NTRK fusion detection. In this study, a total of 4,619 LUAD formalin‐fixed, paraffin‐embedded tissues were collected from patients who underwent biopsy or resection at the Shanghai Chest Hospital during 2017–2019. All specimens were screened for NTRK1 rearrangements using DNA‐based NGS. Thereafter, the cases with NTRK1 rearrangements and cases negative for common driver mutations were analyzed for NTRK1/2/3 fusions using total nucleic acid (TNA)‐based NGS and pan‐TRK IHC. Overall, four NTRK1/2 fusion events were identified, representing 0.087% of the original sample set. At the DNA level, seven NTRK1 rearrangements were identified, while only two TPM3‐NTRK1 fusions were confirmed on TNA‐based NGS as functional. In addition, two NTRK2 fusions (SQSTM1‐NTRK2 and KIF5B‐NTRK2) were identified by TNA‐based NGS in 350 ‘pan‐negative’ cases. Two patients harboring NTRK1/2 fusions were diagnosed with invasive adenocarcinoma, while the other two were diagnosed with adenocarcinoma in situ and minimally invasive adenocarcinoma. All four samples with NTRK fusions were positive for the expression of pan‐TRK. The two samples with NTRK2 fusions showed cytoplasmic staining alone, while the other two samples with NTRK1 fusions exhibited both cytoplasmic and membranous staining. In summary, functional NTRK fusions are found in early‐stage LUAD; however, they are extremely rare. According to this study's results, they are independent oncogenic drivers, mutually exclusive with other driver mutations. We demonstrated that NTRK rearrangement analysis using a DNA‐based approach should be verified with an RNA‐based assay.
Intelligent implementation of residential demand response using multiagent system and deep neural networks
Authors: Saeed Faisal , Paul Anand , Ahmed Muhammad Jamal , Gul Malik Junaid Jami , Hong Won‐Hwa , Seo Hyuncheol 
Published: March 2021

AbstractA successful implementation of demand response (DR) always depends on proper policy and their empower technologies. This article proposed an intelligent multiagent system to idealize the residential DR in distributed network. In our model, the primary stakeholders (smart homes and retailers) are demonstrated as a multifunctional intelligent agent. Home agents (HAs) are able to predict and schedule the energy load and retailer agents (RAs) predicts wholesale market price, sells energy to HAs. Both HAs and RAs are modeled to predict the real‐time pricing. Deep neural networks, that is, long short‐term memory network and hybrid CNN‐LSTM are used to predict the electricity load and energy price. Simulation results present good accuracy. Proposed work is compared with existing model w.r.t RMSE, MSE, and MAE. Comparison shows our model outperformed the existing models.
Systematic evaluation of a panel of 30 synthetic cannabinoid receptor agonists structurally related to MMB‐4en‐PICA, MDMB‐4en‐PINACA, ADB‐4en‐PINACA, and MMB‐4CN‐BUTINACA using a combination of binding and different CB1 receptor activation assays—Part II: Structure activity relationship assessment via a β‐arrestin recruitment assay
Authors: Grafinger Katharina Elisabeth , Cannaert Annelies , Ametovski Adam , Sparkes Eric , Cairns Elizabeth , Banister Samuel D. , Auwärter Volker , Stove Christophe P. 
Published: March 2021

AbstractSynthetic cannabinoid receptor agonists (SCRAs) are the second largest class of new psychoactive substances (NPS) and are associated with serious adverse effects and even death. Despite this, little pharmacological data are available for many of the most recent SCRAs. This study consists of three different parts, aiming to systematically evaluate a panel of 30 SCRAs using binding and different in vitro human cannabinoid 1 receptor (CB1) activation assays. The present Part II investigated the SCRA analogs for their CB1 activation via a β‐arrestin recruitment assay. The panel was systematically designed to include key structural sub‐features of recent SCRAs. Thus, the 4‐pentenyl tail of MMB‐4en‐PICA and MDMB‐4en‐PINACA was retained while incorporating varying head groups from other prevalent SCRAs, including amides and esters of L‐valine, L‐tert‐leucine, and L‐phenylalanine, and adamantyl and cumyl moieties. All 30 SCRAs activated CB1, with indazoles generally showing the greatest potency (EC50 = 1.88–281 nM), followed by indoles (EC50 = 11.5–2293 nM), and the corresponding 7‐azaindoles (EC50 = 62.4–9251 nM). Several subunit‐linked structure–activity relationships were identified: (i) tert‐leucine‐functionalized SCRAs were more potent than the corresponding valine derivatives; (ii) no major difference in potency or efficacy was observed between tert‐leucine/valine‐derived amides and the corresponding methyl esters; however, phenylalanine analogs were affected by this change; and (iii) minor structural changes to the 4‐pentenyl substituent had little influence on activity. These findings elucidate structural features that modulate the CB1 activation potential of currently prevalent SCRAs and a systematic panel of analogs, some of which may appear in NPS markets in future.
When are hypotheses useful in ecology and evolution?
Authors: Betts Matthew G. , Hadley Adam S. , Frey David W. , Frey Sarah J. K. , Gannon Dusty , Harris Scott H. , Kim Hankyu , Kormann Urs G. , Leimberger Kara , Moriarty Katie , Northrup Joseph M. , Phalan Ben , Rousseau Josée S. , Stokely Thomas D. , Valente Jonathon J. , Wolf Chris , Zárrate‐Charry Diego 
Published: March 2021

AbstractResearch hypotheses have been a cornerstone of science since before Galileo. Many have argued that hypotheses (1) encourage discovery of mechanisms, and (2) reduce bias—both features that should increase transferability and reproducibility. However, we are entering a new era of big data and highly predictive models where some argue the hypothesis is outmoded. We hypothesized that hypothesis use has declined in ecology and evolution since the 1990s, given the substantial advancement of tools further facilitating descriptive, correlative research. Alternatively, hypothesis use may have become more frequent due to the strong recommendation by some journals and funding agencies that submissions have hypothesis statements. Using a detailed literature analysis (N = 268 articles), we found prevalence of hypotheses in eco–evo research is very low (6.7%–26%) and static from 1990–2015, a pattern mirrored in an extensive literature search (N = 302,558 articles). Our literature review also indicates that neither grant success nor citation rates were related to the inclusion of hypotheses, which may provide disincentive for hypothesis formulation. Here, we review common justifications for avoiding hypotheses and present new arguments based on benefits to the individual researcher. We argue that stating multiple alternative hypotheses increases research clarity and precision, and is more likely to address the mechanisms for observed patterns in nature. Although hypotheses are not always necessary, we expect their continued and increased use will help our fields move toward greater understanding, reproducibility, prediction, and effective conservation of nature.
Asymmetric Organocatalytic Synthesis of aza‐Spirocyclic Compounds from Isothiocyanates and Isocyanides
Authors: Laviós Adrián , Sanz‐Marco Amparo , Vila Carlos , Blay Gonzalo , Pedro José R. 
Published: March 2021

AbstractThe spirocyclic motif is present in natural products, chiral ligands, and compounds of pharmacological interest. Isothiocyanates as well as isocyanides bearing electron‐withdrawing groups in the α‐position can be deprotonated and react as formal dipoles on account of the presence of a nucleophilic carbanion and an electrophilic atom in the isothiocyanate or isocyanide functional groups. In the last years a number of procedures involving the formal [3+2] cycloaddition reaction of isothiocyanates or isocyanides with cyclic compounds bearing electrophilic exocyclic double bonds have been developed for the enantioselective synthesis of aza‐spirocyclic compounds. Among them, organocatalysis has played a predominant role in the development of asymmetric versions for these reactions. The synthesis of spirooxindoles by using this methodology has received especial attention, although other spirocyclic scaffolds are available depending on the structure of the dipolarophiles and the formal isothiocyanate and isocyanide dipoles.
Facile Synthesis of Spirocyclic Lactams via [3+2] and [3+3] Aza‐Annulation Reactions
Authors: Hayrapetyan Davit , Stepanova Valeriya 
Published: March 2021

AbstractSpirocyclic pyrrolidones and piperidones were synthesized starting from readily available α‐ketolactones and α‐ketolactams employing [3+2]‐ and [3+3]‐aza‐annulation reactions. Annulation reactions proceeded with good yields and further reduction of the exocyclic C=C double bond of the enamide moiety proceeded with excellent diastereoselectivity. Overall, one C−C and two C−N bonds, as well as three new stereocenters were created in a diastereoselective manner resulting in a fast upbuild of molecular complexity.
Para‐Functionalization of N‐Substituted 4‐amino[2.2]paracyclophanes by Regioselective Formylation
Authors: Felder Simon , Micouin Laurent , Benedetti Erica 
Published: March 2021

AbstractHerein, we report a simple and convenient procedure to prepare para‐disubstituted [2.2]paracyclophanes in a straightforward manner. Our approach relies on a regioselective formylation of N‐substituted 4‐amino[2.2]paracyclophanes, which allows an easy access to a series of products incorporating a reactive aldehyde function para to the electron‐donating group. These compounds can be engaged in a variety of orthogonal late‐stage derivatization processes involving either the carbonyl group or the amine function, and can serve as precursors to rapidly access more complex paracyclophane derivatives. Control of planar chirality is also possible by performing a kinetic resolution of key racemic intermediates through asymmetric transfer hydrogenation. The formylation can be run on a synthetically useful scale, thus confirming the practical applicability of our method.