bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in Asymmetric Di‐and Trifluoromethylthiolation, and Di‐ and Trifluoromethoxylation Reactions
Authors: Hardy Melissa A. , Chachignon Hélène , Cahard Dominique 
Published: February 2019

AbstractMethods to introduce fluorine atoms or fluoroalkyl groups are highly valuable to the design and development of biologically active compounds. To date, majority of fluorinated pharmaceuticals and agrochemicals bear a fluorine atom or CF3 group at a non‐stereogenic center. The development of methods for the construction of new, emerging fluorinated motifs, in particular those combining a heteroatom and a fluorocarbon moiety have witnessed tremendous advancement in recent years; however, a challenging problem is the stereocontrol of a carbon center featuring such fluorinated motifs. This review aims to summarize the advancement in the asymmetric construction of trifluoromethylthio‐ and trifluoromethoxy compounds as well as their difluoromethyl analogues. Both the direct installation of the O−Rf and S−Rf groups (Rf=CF3, CF2H) and the exploitation of building blocks featuring these groups are detailed.
Variation in SIPA1L2 is correlated with phenotype modification in Charcot– Marie– Tooth disease type 1A
Authors: Tao Feifei , Beecham Gary W. , Rebelo Adriana P. , Svaren John , Blanton Susan H. , Moran John J. , Lopez‐Anido Camila , Morrow Jasper M. , Abreu Lisa , Rizzo Devon , Kirk Callyn A. , Wu Xingyao , Feely Shawna , Verhamme Camiel , Saporta Mario A. , Herrmann David N. , Day John W. , Sumner Charlotte J. , Lloyd Thomas E. , Li Jun , Yum Sabrina W. , Taroni Franco , Baas Frank , Choi Byung‐Ok , Pareyson Davide , Scherer Steven S. , Reilly Mary M. , Shy Michael E. , Züchner Stephan ,   for the Inherited Neuropathy Consortium
Published: February 2019

ObjectiveGenetic modifiers in rare disease have long been suspected to contribute to the considerable variance in disease expression, including Charcot–Marie–Tooth disease type 1A (CMT1A). To address this question, the Inherited Neuropathy Consortium collected a large standardized sample of such rare CMT1A patients over a period of 8 years. CMT1A is caused in most patients by a uniformly sized 1.5 Mb duplication event involving the gene PMP22.MethodsWe genotyped DNA samples from 971 CMT1A patients on Illumina BeadChips. Genome‐wide analysis was performed in a subset of 330 of these patients, who expressed the extremes of a hallmark symptom: mild and severe foot dorsiflexion strength impairment. SIPA1L2 (signal‐induced proliferation‐associated 1 like 2), the top identified candidate modifier gene, was expressed in the peripheral nerve, and our functional studies identified and confirmed interacting proteins using coimmunoprecipitation analysis, mass spectrometry, and immunocytochemistry. Chromatin immunoprecipitation and in vitro siRNA experiments were used to analyze gene regulation.ResultsWe identified significant association of 4 single nucleotide polymorphisms (rs10910527, rs7536385, rs4649265, rs1547740) in SIPA1L2 with foot dorsiflexion strength (p < 1 × 10−7). Coimmunoprecipitation and mass spectroscopy studies identified β‐actin and MYH9 as SIPA1L2 binding partners. Furthermore, we show that SIPA1L2 is part of a myelination‐associated coexpressed network regulated by the master transcription factor SOX10. Importantly, in vitro knockdown of SIPA1L2 in Schwannoma cells led to a significant reduction of PMP22 expression, hinting at a potential strategy for drug development.Interpretation
SIPA1L2 is a potential genetic modifier of CMT1A phenotypic expressions and offers a new pathway to therapeutic interventions. ANN NEUROL 2019;85:316–330.
Mechanism study of the conversion of esters to high‐octane‐number aromatics over HZSM‐5
Authors: Habibi Navid , Dabbagh Hossein A. 
Published: February 2019

A study of the mechanism of the catalytic transformation of mixed ethyl acetate (EA) + methyl acetate (MA) (50:50 v/v) to hydrocarbons over HZSM‐5 (Si/Al ratio of 9) catalyst was conducted. The reaction was carried out in a continuous fixed‐bed reactor under atmospheric pressure and in the temperature range 250–390°C and with weight hourly space velocity of 3.2 and 4.6 h−1. The distribution of products including monoaromatics, fused ring aromatics and oxygenates was determined using GC‐MS. The product distribution was controlled by temperature. The oxygenate components (kinetically controlled products) were transformed into aromatics (thermodynamically controlled products) with an increase in temperature. The effluents were benzene‐free or with low content of benzene and toluene. Two intermediates were proposed for this conversion to hydrocarbons over HZSM‐5: cyclobutane‐1,3‐dione and/or acetic acid (AA) as ketene source. Furthermore, AA and mesityl oxide (MO) were selected as potential intermediates in the transformation of mixed EA + MA into hydrocarbons over HZSM‐5. It is suggested that ketene dimerization, the phenolic pool and the condensation reaction between ketene and MO are the probable mechanism routes for AA conversion. Aldol condensation, Michael addition, cracking, isomerization and ketene formation are the presumable pathways for MO conversion over HZSM‐5.
MAO‐free and extremely active catalytic system for ethylene tetramerization
Authors: Kim Tae Hee , Lee Hyun Mo , Park Hee Soo , Kim Sung Dong , Kwon Su Jin , Tahara Atsushi , Nagashima Hideo , Lee Bun Yeoul 
Published: February 2019

The original Sasol catalytic system for ethylene tetramerization is composed of a Cr source, a PNP ligand, and MAO (methylaluminoxane). The use of expensive MAO in excess has been a critical concern in commercial operation. Many efforts have been made to replace MAO with non‐coordinating anions (e.g., [B(C6F5)4]−); however, most of such attempts were unsuccessful. Herein, an extremely active catalytic system that avoids the use of MAO is presented. The successive addition of two equivalent [H(OEt2)2]+[B(C6F5)4]− and one equivalent CrCl3(THF)3 to (acac)AlEt2 and subsequent treatment with a PNP ligand [CH3(CH2)16]2C(H)N(PPh2)2 (1) yielded a complex presumably formulated as [1‐CrAl (acac)Cl3(THF)]2+[B(C6F5)4]−2, which exhibited high activity when combined with iBu3Al (1120 kg/g‐Cr/h; ~4 times that of the original Sasol system composed of Cr (acac)3, iPrN(PPh2)2, and MAO). Via the introduction of bulky trialkylsilyl substituents such as –SiMe3, –Si(nBu)3, or –SiMe2(CH2)7CH3 at the para‐position of phenyl groups in 1 (i.e., by using [CH3(CH2)16]2C(H)N[P(C6H4‐p‐SiR3)2]2 instead of 1), the activities were dramatically improved, i.e., tripled (2960–3340 kg/g‐Cr/h; more than 10 times that of the original Sasol system). The generation of significantly less PE (<0.2 wt%) even at a high temperature is another advantage achieved by the introduction of bulky trialkylsilyl substituents. NMR studies and DFT calculations suggest that increase of the steric bulkiness on the alkyl‐N and P‐aryl moieties restrict the free rotation around (alkyl)N–P (aryl) bonds, which may cause the generation of more robust active species in higher proportion, leading to extremely high activity along with the generation of a smaller amount of PE.
Controlled isoprene polymerization mediated by iminopyridine‐iron (II) acetylacetonate pre‐catalysts
Authors: Zhao Mengmeng , Wang Liang , Mahmood Qaiser , Jing Chuyang , Zhu Guangqian , Zhang Xianhui , Wang Xiaowu , Wang Qinggang 
Published: February 2019

A ligand controlled stereoselective polymerization of isoprene has been developed. A series of (aryl/alkyl)‐iminopyridine iron (II) acetylacetonate complexes: (aryl = Ph Fe1; alkyl = CH2Ph Fe2, CH (Ph)2 Fe3, CH (Me)2 Fe4, C (Me)3 Fe5, C (Me)2CH2C(Me)3 Fe6), has been prepared in which steric and electronic substituents systematically modified to investigate their influences for isoprene polymerization. The molecular structure of representative complex Fe2 was confirmed by single crystal X‐ray diffraction and, revealed a distorted octahedral geometry at iron center. On treatment with methylaluminoxane (MAO), Fe1–Fe6 displayed low (Fe5 & Fe6) to high activities (Fe1–Fe4) with quantitative monomer conversion (>99%) for isoprene polymerization producing polyisoprene of high molecular weight (up to 2.0 × 105 g/mol) and unimodal molecular weight distribution (1.4–3.3). Specifically, complex Fe2 (alkyl = CH2Ph) displayed the highest activity of 7.0 × 106 g (mol of Fe)−1 h−1 with 85% conversion of monomer over run time of 10 min at 25 °C. While, Fe6 catalyzed polyisoprene possessed high content of trans‐1,4 unit (up to 87%). Furthermore, the influence of the reaction parameters and the nature of the ligands on the catalytic activities and microstructural properties of the polymer were investigated in detail.
Mode hunting through active information
Authors: Díaz‐Pachón Daniel Andrés , Sáenz Juan Pablo , Rao J. Sunil , Dazard Jean‐Eudes 
Published: February 2019

AbstractWe propose a new method to find modes based on active information. We develop an algorithm called active information mode hunting (AIMH) that, when applied to the whole space, will say whether there are any modes present and where they are. We show AIMH is consistent and, given that information increases where probability decreases, it helps to overcome issues with the curse of dimensionality. The AIMH also reduces the dimensionality with no resource to principal components. We illustrate the method in three ways: with a theoretical example (showing how it performs better than other mode hunting strategies), a real dataset business application, and a simulation.
Impact of visceral pleural invasion on the association of extent of lymphadenectomy and survival in stage I non‐small cell lung cancer
Authors: Wo Yang , Zhao Yandong , Qiu Tong , Li Shicheng , Wang Yuanyong , Lu Tong , Qin Yi , Song Guisong , Miao Shuncheng , Sun Xiao , Liu Ao , Kong Dezhi , Dong Yanting , Leng Xiaoliang , Du Wenxing , Jiao Wenjie 
Published: February 2019

AbstractVisceral pleural invasion (VPI) has been identified as an adverse prognostic factor for non‐small cell lung cancer (NSCLC). Accurate nodal staging for NSCLC correlates with improved survival, but it is unclear whether tumors with VPI require a more extensive lymph nodes (LNs) dissection to optimize survival. We aimed to evaluate the impact of VPI status on the optimal extent of LNs dissection in stage I NSCLC, using the Surveillance, Epidemiology, and End Results (SEER) database. We identified 9297 surgically treated T1‐2aN0M0 NSCLC patients with at least one examined LNs. Propensity score matching was conducted to balance the baseline clinicopathologic characteristics between the VPI group and non‐VPI group. Log‐rank tests along with Cox proportional hazards regression methods were performed to evaluate the impact of extent of LNs dissection on survival. VPI was correlated with a significant worse survival, but there was no significant difference in survival rate between PL1 and PL2. Patients who underwent sublobectomy had slightly decreased survival than those who underwent lobectomy. Pathologic LNs examination was significantly correlated with survival. Examination of 7‐8 LNs and 14‐16 LNs conferred the lowest hazard ratio for T1‐sized/non‐VPI tumors (stage IA) and T1‐sized/VPI tumors (stage IB), respectively. The optimal extent of LNs dissection varied by VPI status, with T1‐sized/VPI tumors (stage IB) requiring a more extensive LNs dissection than T1‐sized/non‐VPI tumors (stage IA). These results might provide guidelines for surgical procedure in early stage NSCLC.
Crusted (Norwegian) scabies as a strong marker of adult T‐cell leukemia/lymphoma in HTLV‐1 infection
Authors: Bimbi César , Brzezinski Piotr , Sokolowska‐Wojdylo Malgorzata 
Published: February 2019

Key Clinical MessageWe present a rare case of crusted scabies in an human T‐cell lymphotropic virus type 1 (HTLV‐1) infected woman prior to onset of adult T‐cell leukemia/lymphoma (ATL). We highlight the importance of this rare form of scabies as a prediagnostic sign of ATL, requiring high suspicion and monitoring of possible symptoms for early detection of ATL.
Ultrasound and Sonochemistry for Radical Polymerization: Sound Synthesis
Authors: McKenzie Thomas G. , Karimi Fatemeh , Ashokkumar Muthupandian , Qiao Greg G. 
Published: February 2019

AbstractThe use of ultrasound as an external stimulus for promoting polymerization reactions has received increasing attention in recent years. In this Review article, the fundamental processes that can lead to either the homolytic cleavage of polymer chains, or the sonolysis of solvent (or other) small molecules, under the application of ultrasound are described. These reactions promote the production of reactive radicals, which can be utilized in chain‐growth radical polymerizations under the right conditions. A full historical overview of the development of ultrasound‐assisted radical polymerization is provided, with special attention given to the recently described systems that are “controlled” by methods of reversible (radical) deactivation. Perspectives are shared on what challenges still remain in polymer sonochemistry, as well as new areas that are yet to be explored.
The rationale, design, and methods of a randomized, controlled trial to evaluate the efficacy and safety of an active strategy for the diagnosis and treatment of acute pulmonary embolism during exacerbations of chronic obstructive pulmonary disease
Authors: Jiménez David , Agustí Alvar , Monreal Manuel , Otero Remedios , Huisman Menno V. , Lobo José L. , Quezada Andrés , Jara‐Palomares Luis , Hernando Ascensión , Tabernero Eva , Marcos Pedro , Ruiz‐Artacho Pedro , Ballaz Aitor , Bertoletti Laurent , Couturaud Francis , Yusen Roger ,   on behalf of the SLICE investigators
Published: February 2019

IntroductionSome previous studies have suggested a high prevalence of pulmonary embolism (PE) during exacerbations of chronic obstructive pulmonary disease (ECOPD). The SLICE trial aims to assess the efficacy and safety of an active strategy for the diagnosis and treatment of PE (vs usual care) in patients hospitalized because of ECOPD.MethodsSLICE is a phase III, prospective, international, multicenter, randomized, open‐label, and parallel‐group trial. A total of 746 patients hospitalized because of ECOPD will be randomized in a 1:1 fashion to receive either an active strategy for the diagnosis and anticoagulant treatment of PE or usual care (ie, standard care without any diagnostic test for diagnosing PE). The primary outcome is a composite of all‐cause death, non‐fatal (recurrent) venous thromboembolism (VTE), or readmission for ECOPD within 90 days after enrollment. Secondary outcomes are (a) death from any cause within 90 days after enrollment, (b) non‐fatal (recurrent) VTE within 90 days after enrollment, (c) readmission within 90 days after enrollment, and (d) length of hospital stay.ResultsEnrollment started in September 2014 and is expected to proceed until 2020. Median age of the first 443 patients was 71 years (interquartile range, 64‐78), and 26% were female.ConclusionsThis multicenter trial will determine the value of detecting PEs in patients with ECOPD. This has implications for COPD patient morbidity and mortality.
Trial registration number: NCT02238639.
A randomized study to improve care for young women with breast cancer at community and academic medical oncology practices in the United States: The Young and Strong study
Authors: Partridge Ann H. , Ruddy Kathryn J. , Barry William T. , Greaney Mary L. , Ligibel Jennifer A. , Sprunck‐Harrild Kim M. , Rosenberg Shoshana M. , Baker Emily L. , Hoverman J. Russell , Emmons Karen M. 
Published: February 2019

BackgroundThe authors conducted a cluster randomized study to determine the effect of an exportable educational intervention for young women with breast cancer (YWI) on improving care.MethodsSites were randomized 1:1 to the YWI or a contact time control physical activity intervention (PAI) stratified by academic or community site. Up to 15 women aged ≤45 years with newly diagnosed breast cancer were enrolled at each of 14 academic sites and 10 were enrolled at each of 40 community sites. The primary endpoint, attention to fertility, was ascertained by medical record review. Statistical inferences concerning the effect of the intervention used general estimating equations for clustered data.ResultsA total of 467 patients across 54 sites were enrolled between July 2012 and December 2013. The median age of the patients at the time of diagnosis was 40 years (range, 22‐45 years). Attention to fertility by 3 months was observed in 55% of patients in the YWI and 58% of patients in the PAI (P = .88). Rates were found to be strongly correlated with age (P < .0001), and were highest in patients aged <30 years. Attention to genetics was similar (80% in the YWI and 81% in the PAI), whereas attention to emotional health was higher in patients in the YWI (87% vs 76%; estimated odds ratio, 2.63 [95% confidence interval, 1.20‐5.76; P = .016]). Patients rated both interventions as valuable in providing education (64% in the YWI and 63% in the PAI).ConclusionsThe current study failed to demonstrate differences in attention to fertility with an intervention to improve care for women with breast cancer, although attention to fertility was found to be higher than expected in both groups and emotional health was improved in the YWI group. Greater attention to young women with breast cancer in general may promote more comprehensive care for this population.
Use of Population Pharmacokinetic Analyses Among FDA‐Approved Biologics
Authors: Ogasawara Ken , Alexander G. Caleb 
Published: February 2019

AbstractBiologics, especially monoclonal antibodies, are increasingly important in the pharmaceutical marketplace. Population pharmacokinetic (PK) analyses could be useful to guide the need for dose adjustments among special populations, yet it is unknown how commonly such analyses are performed during biologics development. We summarized the characteristics of population PK models of biologics and examined their role in informing the drug labels. To do so, we extracted relevant characteristics of 86 biologics approved by the U.S. Food and Drug Administration's Center for Drug Evaluation and Research between 2003 and 2017. Ninety‐four percent of monoclonal antibodies (51 of 54 biologics), 75% of fusion proteins with Fc receptor (6 of 8 biologics), and 33% of other proteins (8 of 24 biologics) included population PK analyses. Of these analyses, approximately half (45%) used a 2‐compartment model with linear clearance as the base model structure. Body size was the most frequently included covariate in the final models (included in 94% of the 64 biologics in which covariate analysis was performed), although age (11%), sex (35%), race (26%), and renal function (27%) were also included in some models. In 70% to 90% of cases in which the effect of these covariates was examined, information regarding the effect of these on PK was included in the label. These results suggest that population PK analyses provide important information about the impact of intrinsic factors on the PK in the label of biologics by the U.S. Food and Drug Administration.
Using Xenopus laevis Oocytes to Functionally Characterize Plant Transporters
Authors: Pike Sharon , Matthes Michaela S. , McSteen Paula , Gassmann Walter 
Published: February 2019

AbstractFunctionally characterizing plant membrane transport proteins is challenging. Typically, heterologous systems are used to study them. Immature eggs (oocytes) of the South African clawed frog Xenopus laevis are considered an ideal expression system for such studies. These large oocytes have a low number of endogenous transport systems in their plasma membranes and highly express foreign mRNA; the oocyte plasma membrane is the default destination of integral membrane proteins that lack recognized organellar sorting signals. These features facilitate almost background‐free characterization of putative plant membrane transporters. Here we describe how to isolate Xenopus laevis oocytes, prepare capped sense RNA (cRNA) of the maize boron importer TASSEL‐LESS1 (TLS1) as an example, microinject the cRNA into the isolated oocytes, and functionally assess the boron import capabilities of TLS1 in an oocyte swelling assay. These protocols can be easily adapted to study other plant and non‐plant transporters with putative import function. © 2019 by John Wiley & Sons, Inc.
Tandem Affinity Purification and Mass Spectrometry (TAP‐MS) for the Analysis of Protein Complexes
Authors: Adelmant Guillaume , Garg Brijesh K. , Tavares Maria , Card Joseph D. , Marto Jarrod A. 
Published: February 2019

AbstractAffinity purification followed by mass spectrometry has become the technique of choice to identify binding partners in biochemical complexes isolated from a physiologic cellular context. In this report we detail our protocol for tandem affinity purification (TAP) primarily based on the use of the FLAG and HA peptide epitopes, with a particular emphasis on factors affecting yield and specificity, as well as steps to implement an automated version of the TAP procedure. © 2019 by John Wiley & Sons, Inc.
Study on the salivation effect of encapsulated food products containing Sichuan pepper oil
Authors: Ryo Koufuchi , Kaneko Mie , Takahashi Kei , Ono Hiroyuki , Ogasawara Tomohiko , Abe Michiro , Saito Ichiro 
Published: February 2019

AbstractSichuan pepper is a plant belonging to the genus Zanthoxylum and family rue. To evaluate whether Sichuan pepper oil boosts saliva secretion using an encapsulated food product containing the oil in subjects presenting with mouth dryness. We evaluated subjective symptoms that changed with a decrease in salivary secretion in the subjects by evaluating the number of Candida colonies and by conducting interviews. The study results demonstrated that salivary secretion increased by 39.4% ± 37.6% after single ingestion of the product, and an additional 8.7% ± 13.2% and 6.3% ± 31.2% following continuous ingestion over 2 and 4 weeks, respectively. These findings suggested that the product rapidly promotes and maintains salivation. Regarding the proliferation of Candida colonies in subjects with mouth dryness, a negative correlation was observed between Candida colony number and salivary secretion quantity. Additionally, interviews revealed that subjective symptoms, such as mouth dryness, discomfort and pain in the mouth, difficulty swallowing the saliva, and feeling of stickiness in the mouth, improved shortly after single ingestion of the product, and mouth dryness was reduced by continuous consumption of the product. These findings indicated that the product studied promotes rapid salivary secretion, is effective in reducing the number of oral Candida colonies, and improves subjective symptoms such as mouth dryness.