bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Asymmetric Anchoring Groups on Electronic Transport in Hybrid Metal/Molecule/Graphene Single Molecule Junctions
Authors: He Chunhui , Zhang Qian , Fan Yinqi , Zhao Cezhou , Zhao Chun , Ye Jingyao , Dappe Yannick J. , Nichols Richard J. , Yang Li
Published: May 2019

A combined experimental and theoretical study on molecular junctions with asymmetry in both the electrode type and in the anchoring group type is presented. A scanning tunnelling microscope is used to create the “asymmetric” Au‐S‐(CH2)n‐COOH‐graphene molecular junctions and determine their conductance. The measurements are combined with electron transport calculations based on density functional theory (DFT) to analyze the electrical conductance and its length attenuation factor from a series of junctions of different molecular length (n). These results show an unexpected trend with a rather high conductance and a smaller attenuation factor for the Au‐S‐(CH2)n‐COOH‐graphene configuration compared to the equivalent junction with the “symmetrical” COOH contacting using the HOOC‐(CH2)n‐COOH series. Owing to the effect of the graphene electrode, the attenuation factor is also smaller than the one obtained for Au/Au electrodes. These results are interpreted through the relative molecule/electrode couplings and molecular level alignments as determined with DFT calculations. In an asymmetric junction, the electrical current flows through the less resistive conductance channel, similarly to what is observed in the macroscopic regime.
Clopidogrel Drug Interactions and Serious Bleeding: Generating Real‐World Evidence via Automated High‐Throughput Pharmacoepidemiologic Screening
Authors: Leonard Charles E. , Zhou Meijia , Brensinger Colleen M. , Bilker Warren B. , Soprano Samantha E. , Pham Nguyen Thanh Phuong , Nam Young Hee , Cohen Jordana B. , Hennessy Sean
Published: May 2019

Few population‐based studies have examined bleeding associated with clopidogrel drug–drug interactions (DDIs). We sought to identify precipitant drugs taken concomitantly with clopidogrel (an object drug) that increased serious bleeding rates. We screened 2000–2015 Optum commercial health insurance claims to identify DDI signals. We performed self‐controlled case series studies for clopidogrel plus precipitant pairs, examining associations with gastrointestinal bleeding or intracranial hemorrhage. To distinguish native bleeding effects of a precipitant, we reexamined associations using pravastatin as a negative control object drug. Among 431 analyses, 28 clopidogrel plus precipitant pairs were statistically significantly positively associated with serious bleeding. Ratios of rate ratios ranged from 1.13–3.94. Among these pairs, 13 were expected given precipitant drugs alone increased and/or were harbingers of serious bleeding. The remaining 15 pairs constituted new DDI signals, none of which are currently listed in two major DDI knowledge bases.
LED‐Illuminated NMR Spectroscopy: A Practical Tool for Mechanistic Studies of Photochemical Reactions
Authors: Ji Yining , DiRocco Daniel A. , Kind Jonas , Thiele Christina M. , Gschwind Ruth M. , Reibarkh Mikhail
Published: May 2019

This Concept article highlights the development of a novel analytical tool, LED‐NMR (a combination of in situ light illumination using a light‐emitting diode and NMR spectroscopy) and its variant UVNMR (LED‐NMR coupled with UV/Vis absorption spectroscopy), as well as their applications in the mechanistic investigation of light‐induced transformations. The utility of these new tools has been demonstrated by providing rich kinetic and structural data of reaction species offering mechanistic insights into photochemical and photocatalytic reactions. Furthermore, NMR actinometry has been recently developed as a practical and simple method for quantum yield measurements. Quantum yield is an important parameter in photo‐induced processes, but is rarely measured in practice because of the barriers associated with traditional actinometry. These new tools and techniques streamline measurements of the quantum efficiency while affording informative mechanistic insights into photochemical reactions. We anticipate these techniques will enable chemists to further advance the rapidly emerging photochemistry field.
Conformational Control and Photophysical Properties of Methylene‐Tethered Bis[(naphthalene‐2‐yl)vinyl]benzenes
Authors: Watanabe Shoya , Yamanishi Katsunori , Tsuji Hayato
Published: May 2019

We have synthesized and isolated three planar dibenzo‐fused oligo(phenylenevinylene) isomers (l‐DBCOPV2, u‐DBCOPV2, and b‐DBCOPV2), which serve as model compounds for rotational conformers of bis[(naphthalene‐2‐yl)vinyl]benzene. Their photophysical properties were examined by UV/Vis absorption and emission spectroscopy, revealing that their emission colors changed from sky‐blue to green depending on the conformation. We have also measured their fluorescence lifetimes and carried out DFT calculations. These investigations revealed a more detailed conformation‐dependent character for l‐DBCOPV2, u‐DBCOPV2, and b‐DBCOPV2: The UV/Vis absorption and emission bands showed bathochromic shifts that increased in the order l‐DBCOPV2<u‐DBCOPV2<b‐DBCOPV2, whereas the extinction coefficients of the absorption decreased in the same order, suggesting a difference in the orbital interactions between the divinylbenzene core and the naphthalene components.
Aerobic Acyloxylation of Allylic C−H Bonds Initiated by a Pd0 Precatalyst with 4,5‐Diazafluoren‐9‐one as an Ancillary Ligand
Authors: Kozack Caitlin V. , Sowin Jennifer A. , Jaworski Jonathan N. , Iosub Andrei V. , Stahl Shannon S.
Published: May 2019

Palladium‐catalyzed allylic C−H oxidation has been widely studied, but most precedents use acetic acid as the coupling partner. In this study, a method compatible with diverse carboxylic acid partners has been developed. Use of a Pd0 precatalyst under aerobic reaction conditions leads to oxidation of Pd0 by O2 in the presence of the desired carboxylic acid to generate a PdII dicarboxylate that promotes acyloxylation of the allylic C−H bond. Good‐to‐excellent yields are obtained with a roughly 1:1 ratio of the alkene and carboxylic acid reagents. Optimized reaction conditions employ 4,5‐diazafluoren‐9‐one (DAF) as a ligand, in combination with a quinone/iron phthalocyanine cocatalyst system to support aerobic catalytic turnover.
Bismuth‐Based Photocatalysts for Solar Photocatalytic Carbon Dioxide Conversion
Authors: Ye Liqun , Deng Yu , Wang Li , Xie Haiquan , Su Fengyun
Published: May 2019

Photocatalytic CO2 conversion into solar fuels is an effective means for simultaneously solving both the greenhouse effect and energy crisis. In the past ten years, bismuth‐based photocatalysts for environmental remediation have experienced a golden period of development. However, solar photocatalytic CO2 conversion has only been developed over the past five years and, until now, no reviews have been published on bismuth‐based photocatalysts for the photocatalytic conversion of CO2. For the first time, solar photocatalytic CO2 conversion systems are reviewed herein. Synthetic methods and photocatalytic CO2 performances of bismuth‐based photocatalysts, including Sillén‐structured BiOX (X=Cl, Br, I); Aurivillius‐structured Bi2MO6 (M=Mo, W); and Scheelite‐structured BiVO4, Bi2S3, BiYO3, and BiOIO3, are summarized. In addition, activity‐enhancing strategies for this photocatalyst family, including oxygen vacancies, bismuth‐rich strategy, facet control, conventional type II heterojunction, Z‐scheme heterojunction, and cocatalyst deposition, are reviewed. Finally, the main mechanistic research methods, such as in situ FTIR spectroscopy and theoretical calculations, are presented. Challenges and research trends reported in studies of bismuth‐based photocatalysts for photocatalytic CO2 conversion are discussed and summarized.
Give students with disabilities a full campus experience
Authors: Hope Joan
Published: May 2019

The University of Iowa REACH Program serves students with disabilities such as autism, intellectual disabilities, and learning disabilities as they transition to adulthood. Director Bill Loyd shared what makes the certificate program a success. “The university puts a premium on diversity, and our students add to that,” he said.
In vitro Phase I metabolism of indazole carboxamide synthetic cannabinoid MDMB‐CHMINACA via human liver microsome incubation and high‐resolution mass spectrometry
Authors: Presley Brandon C. , Logan Barry K. , Jansen‐Varnum Susan A.
Published: May 2019

Synthetic cannabinoids have proliferated over the last decade and have become a major public health and analytical challenge, critically impacting the clinical and forensic communities. Indazole carboxamide class synthetic cannabinoids have been particularly rampant, and exhibit severe toxic effects upon consumption due to their high binding affinity and potency at the cannabinoid receptors (CB1 and CB2). MDMB‐CHMINACA, methyl 2‐[1‐(cyclohexylmethyl)‐1H‐indazole‐3‐carboxamido]‐3,3‐dimethylbutanoate, a compound of this chemical class, has been identified in forensic casework and is structurally related to several other synthetic cannabinoids. This study presents the first extensive report on the Phase I metabolic profile of MDMB‐CHMINACA, a potent synthetic cannabinoid. The in vitro metabolism of MDMB‐CHMINACA was determined via incubation with human liver microsomes and high‐resolution mass spectrometry. The accurate masses of precursor and fragments, mass error (ppm), and chemical formula were obtained for each metabolite. Twenty‐seven metabolites were identified, encompassing twelve metabolite types. The major biotransformations observed were hydroxylation and ester hydrolysis. Hydroxylations were located predominantly on the cyclohexylmethyl (CHM) moiety. Ester hydrolysis was followed by additional biotransformations, including dehydrogenation; mono‐ and dihydroxylation and ketone formation, each with dehydrogenation. Minor metabolites were identified and reported. The authors propose that CHM‐monohydroxylated metabolites specific to MDMB‐CHMINACA are the most suitable candidates for implementation into bioanalytical assays to demonstrate consumption of this synthetic cannabinoid. Due to the structural similarity of MDMB‐CHMINACA and currently trending synthetic cannabinoids whose metabolic profiles have not been reported, the results of this study can be used as a guide to predict their metabolic pathways.
Sub‐micrometer insights into the cytoskeletal dynamics and ultrastructural diversity of butterfly wing scales
Authors: Day Christopher R. , Hanly Joseph J. , Ren Anna , Martin Arnaud
Published: May 2019

Background

The color patterns that adorn lepidopteran wings are ideal for studying cell type diversity using a phenomics approach. Color patterns are made of chitinous scales that are each the product of a single precursor cell, offering a 2D system where phenotypic diversity can be studied cell by cell, both within and between species. Those scales reveal complex ultrastructures in the sub‐micrometer range that are often connected to a photonic function, including iridescent blues and greens, highly reflective whites, or light‐trapping blacks.

Results

We found that during scale development, Fascin immunostainings reveal punctate distributions consistent with a role in the control of actin patterning. We quantified the cytoskeleton regularity as well as its relationship to chitin deposition sites, and confirmed a role in the patterning of the ultrastructures of the adults scales. Then, in an attempt to characterize the range and variation in lepidopteran scale ultrastructures, we devised a high‐throughput method to quickly derive multiple morphological measurements from fluorescence images and scanning electron micrographs. We imaged a multicolor eyespot element from the butterfly Vanessa cardui (V. cardui), taking approximately 200 000 individual measurements from 1161 scales. Principal component analyses revealed that scale structural features cluster by color type, and detected the divergence of non‐reflective scales characterized by tighter cross‐rib distances and increased orderedness.

Conclusion

We developed descriptive methods that advance the potential of butterfly wing scales as a model system for studying how a single cell type can differentiate into a multifaceted spectrum of complex morphologies. Our data suggest that specific color scales undergo a tight regulation of their ultrastructures, and that this involves cytoskeletal dynamics during scale growth.
Burden or Opportunity? Parent Experiences When Approached for Research in a Pediatric Intensive Care Unit
Authors: Paquette Erin , Shukla Avani , Davidson Jacob , Rychlik Karen , Davis Matthew
Published: May 2019

Despite an ongoing need for pediatric research, low study enrollment may impede study completion, particularly in critical care. We conducted a prospective cross‐sectional survey and chart review study to assess parent experiences with research in a pediatric intensive care unit (PICU). Of the 80 parents who completed the study survey, 54% were approached to participate in a research study in the PICU, and 93% agreed to participate. Motivators included altruism, low burden, low risk, and research that would benefit the child. Barriers included risks to the child, the child's being too sick to participate, feeling overwhelmed, not having enough time to participate, the research's being burdensome, and the research's not being explained well. PICU parents had mostly favorable attitudes toward research participation. Compared with non‐Hispanic survey respondents, respondents of Hispanic ethnicity less often reported having been approached for research, which further evidences the need to track research recruitment processes to help avoid underinclusion of members of minority populations.
The Role of Inclusion Benefits in Ethics Committee Assessment of Research Studies
Authors: Rennie Stuart , Day Suzanne , Mathews Allison , Gilbertson Adam , Luseno Winfred K. , Tucker Joseph D. , Henderson Gail E.
Published: May 2019

The relationship between risks and benefits is central to the ethics of research involving human participants. Traditionally, to be ethically justifiable, risks should be reasonable in relation to anticipated benefits (if any) to subjects and to the potential social benefits resulting from research. This calculus is being further complicated by findings from an increasing number of social science studies that reveal that prospective and actual research participants frequently describe various types of inclusion benefits (for example, personal benefits such as access to or improved health care, increased knowledge about their disease or condition, and greater solidarity with the local community) as important to them. What is the ethical significance of such inclusion benefits, particularly those nonmedical in nature, for research ethics committees' risk‐benefit assessment of research studies? We argue that, unless participants are clearly mistaken in their perceptions, ethics committees should take these types of inclusion benefits into account, and we suggest a few ways this might look in practice.
Species‐specific responses to habitat conversion across scales synergistically restructure Neotropical bird communities
Authors: Frishkoff Luke O. , Karp Daniel S.
Published: May 2019

Ecologists are increasingly exploring methods for preserving biodiversity in agricultural landscapes. Yet because species vary in how they respond to habitat conversion, ecological communities in agriculture and more natural habitats are often distinct. Unpacking the heterogeneity in species responses to habitat conversion will be essential for predicting and mitigating community shifts. Here, we analyze two years of bird censuses at 150 sites across gradients of local land cover, landscape forest amount and configuration, and regional precipitation in Costa Rica to holistically characterize species responses to habitat conversion. Specifically, we used Poisson‐binomial mixture models to (1) delineate groups of species that respond similarly to environmental gradients, (2) explore the relative importance of local vs. landscape‐level habitat conversion, and (3) determine how landscape context influences species’ local habitat preferences. We found that species fell into six groups: habitat generalists, abundant and rare forest specialists, and three groups of agricultural specialists that differed in their responses to landscape forest cover, fragmentation, and regional precipitation. Birds were most sensitive to local forest cover, but responses were contingent on landscape context. Specifically, forest specialists benefitted most when local forest cover increased in forested landscapes, while habitat generalists exhibited compensatory dynamics, peaking at sites with either local or landscape‐level forest, but not both. Our study demonstrates that species responses to habitat conversion are complex but predictable. Characterizing species‐level responses to environmental gradients represents a viable approach for forecasting the winners and losers of global change and designing interventions to minimize the ongoing restructuring of Earth's biota.
Predicting species distributions: unifying model selection and scale optimization for multi‐scale occupancy models
Authors: Stevens Bryan S. , Conway Courtney J.
Published: May 2019

Geographic distributions are a basic component of a species’ ecology, and predicting distributions is a fundamental task of conservation and resource management. Reliable prediction depends on identification of appropriate scales of effect for environmental data, and scale‐optimization techniques are thus desirable to identify optimal scales for predictor variables. Recent statistical developments have also advanced methods of model selection based explicitly on predictive ability, which differ from commonly used methods that regulate model structures via anticipated predictive performance. Such methods are beginning to permeate into species distribution models (SDMs), yet there remains no consensus methodology for developing optimally predictive multi‐scale SDMs when covariate data are collected over a range of scales. Thus, we compared the performance of common approaches for scale optimization and model selection in terms of their ability to produce optimally predictive multi‐scale Bayesian occupancy models for predicting a species distribution, using models of the breeding distribution for King Rails (Rallus elegans) as a case study. Our results demonstrate sizable gains in predictive performance for hierarchical occupancy models selected via their ability to predict out‐of‐sample data using the logarithmic scoring rule, as compared to models selected using information criteria (deviance information criteria [DIC] and Watanabe information criteria [WAIC]). Information criteria commonly selected individual covariates, as well as scales of effect for those covariates, with suboptimal predictive performance. Performance of models selected using the logarithmic scoring rule was also robust across the method of scale optimization, which was not true for models selected using DIC and WAIC. Thus, we demonstrate empirical benefits of study designs and statistical tools that enable covariate and scale selection based explicitly on predictive ability. Our results also imply that more careful consideration of what constitutes an optimal scale is warranted in many ecological applications, as the meaning of optimal is not independent of the technique used for scale selection.
Divergent memory responses driven by adenoviral vectors are impacted by epitope competition
Authors: Colston Julia M , Hutchings Claire , Chinnakannan Senthil , Highton Andrew , Perez‐Shibayama Christian , Ludewig Burkhard , Klenerman Paul
Published: May 2019

Adenoviral vectors induce robust epitope‐specific CD8+ T cell responses. Within the repertoire of responses generated both conventional memory evolution and the phenomenon of memory inflation are seen. The rules governing which epitopes inflate are not fully known, but may include a role for both antigen processing and competition. To investigate this, we looked at memory generated from vectors targeting the Gp33‐41 (KAVYNFATC/K9C) epitope from the gp of lymphocytic choriomeningitis virus (LCMV) in mice. This well‐described epitope has both the Gp33‐41 and Gp34‐41 epitopes embedded within it. Vaccination with a full‐length gp or a minigene Ad‐Gp33/K9C vector‐induced conventional memory responses against the immunodominant Gp33/K9C epitope but a strong inflationary response against the Gp34/A8C epitope. These responses showed sustained in vivo function, with complete protection against LCMV infectious challenge. Given the unexpected competition between epitopes seen in the minigene model, we further tested epitope competition using the full‐length Ad‐LacZ (β‐galactosidase) model. Generation of an Ad‐LacZ vector with a single amino acid disruption of the inflationary β‐gal96‐103/D8V epitope transformed the β‐gal497‐504/I8V epitope from conventional to inflationary memory. This work collectively demonstrates the importance of epitope competition within adenoviral vector inserts and is of relevance to future studies using adenoviral vectored immunogens.
Antioxidant Properties of Adrenaline in the Presence of Ge‐132
Authors: Filonova Galina E. , Nikolaevskaya Elena N. , Kansuzyan Artem V. , Krylova Irina V. , Egorov Mikhail P. , Jouikov Viatcheslav V. , Syroeshkin Mikhail A.
Published: May 2019

Using cyclic voltammetry, UV and 1H NMR spectroscopy, we have investigated the effect of 2‐carboxyethylgermanium (Ge‐132), the most common germanium‐containing dietary supplement, on the antioxidant activity of adrenaline in aqueous solutions. The complex formed by adrenaline and Ge‐132 is oxidizable at 400 mV more positive potentials compared to non‐coordinated adrenaline which corresponds to its 9 kcal/mol more difficult oxidation. An equilibrium constant of the complex formation was estimated (1300 m–1). It was shown that at the concentrations <10–3 m the complex Ge‐132‐adrenaline is mostly dissociated to the initial compounds, and the influence of Ge‐132 on the antioxidant properties of adrenaline becomes significant only when the former is in excess. Considering that such concentrations are typical for physiological conditions, this fact can be significant in identifying the mechanism of the biological action of Ge‐132 and its interference with the biological catechols.
Regioselective Synthesis of 2‐Arylindoles via Palladium‐Catalyzed Cyclization of Phenylglyoxal and 2‐Anilinoacetophenones with Anilines
Authors: Benitez‐Medina G. Eliad , Ortiz‐Soto Sofía , Cabrera Armando , Amézquita‐Valencia Manuel
Published: May 2019

A versatile route has been developed for the synthesis of 2‐arylindoles using a Pd‐catalyzed tandem process. Under reductive conditions, different 2‐arylindoles were synthesized from phenylglyoxal and aniline. This synthetic methodology involves a tandem reaction of four steps with high regioselectivity. Alternatively, 2‐anilinoacetophenones intermediates also can be using to give access to the corresponding 2‐arylindoles.
Stereoselective Synthesis of Z‐Vinyl Selenides Through the Reaction of Sodium Selenide with Organic Halides and Alkynes
Authors: Pistoia Renan P. , Back Davi F. , Zeni Gilson
Published: May 2019

A practical synthetic approach to the stereoselective synthesis of Z‐vinyl selenides is described through the reaction of sodium selenide with organic halides, followed by the addition to alkynes. The reaction conditions were also successfully applied to the synthesis of selenochromones through the intramolecular version of this methodology by the reaction of 2‐chlorophenylynones with sodium selenide. The synthetic utility of vinyl selenides prepared was proven through the reaction with Kumada, Negishi and Suzuki substrates, giving the corresponding cross‐coupled products in good yields.
Stereoselective Reduction of α‐Fluoro‐β‐keto Esters by NADH and NADPH‐Dependent Ketoreductases
Authors: Green Thomas K. , Damarancha Anil , Vanagel Matthew , Showalter Brandon , Kolberg Sandra , Thompson Alexander
Published: May 2019

Racemic α‐fluoro‐β‐keto esters were stereoselectively transformed to α‐fluoro‐β‐hydroxy esters through dynamic reductive kinetic resolution (DYRKR) using commercially available NAD(P)H‐dependent ketoreductases. Aromatic, alkenyl, and alkyl substrates were all reduced in high optical purities and yields. For most substrates, either anti or syn diastereomers could be produced with high enantiomeric excess, depending on the enzyme employed. The enzyme reactions with ethyl α‐fluoroacetoacetate were conveniently monitored in real time by in situ 19F NMR spectroscopy. These commercially available enzymes provide convenient access to stereoisomers of α‐fluoro‐β‐hydroxy esters from easily accessible racemic substrates.
Communicate the value of study abroad for community college students
Authors: Sutton Halley
Published: May 2019

LOS ANGELES — The benefits of higher education extend beyond what is learned in the classroom. The opportunity to study abroad during their time in college can be a memorable experience for students, one that broadens their horizons. Community colleges might not be the institutions that come to most people's minds when thinking about rich study abroad experiences, but, in fact, community colleges often offer students many options for an international experience.
New statistical methods for the comparison and characterization of particle shape
Authors: Graham David J. , Gadsden Richard J.
Published: May 2019

This paper presents novel methods for robust statistical testing of particle shape data. Shape (the relative lengths of three orthogonal axes) is a key property of sedimentary particles, providing information on provenance, transport history and depositional environment. However, the usefulness of shape data, including the ability to make robust comparisons between samples, has been constrained by the absence of a satisfactory definition of the mean shape for a sample of particles. Such a definition is proposed and used to develop confidence regions for the population mean shape using both parametric (theoretical) and computational (bootstrap) methods. These techniques are based on a transform that permits multivariate statistical methods for the analysis of compositional data to be extended to shape. These techniques are validated with reference to a dataset of 169 clast samples and found to perform well. A statistical test on the mean – using the multivariate extension of Student's t‐test, Hotelling's T2 – is presented. The benefits of the methods presented are demonstrated with reference to a case study. © 2019 John Wiley & Sons, Ltd.
Microglia suppress the secondary progression of autoimmune encephalomyelitis
Authors: Tanabe Shogo , Saitoh Shohei , Miyajima Hisao , Itokazu Takahide , Yamashita Toshihide
Published: May 2019

Secondary progressive multiple sclerosis (SPMS) is an autoimmune disease of the central nervous system (CNS) characterized by progressive motor dysfunction, sensory deficits, and visual problems. The pathological mechanism of SPMS remains poorly understood. In this study, we investigated the role of microglia, immune cells in the CNS, in a secondary progressive form of experimental autoimmune encephalomyelitis (EAE), the mouse model of SPMS. We induced EAE in nonobese diabetic mice and treated the EAE mice with PLX3397, an antagonist of colony stimulating factor‐1 receptor, during secondary progression in order to deplete microglia. The results showed that PLX3397 treatment significantly exacerbated secondary progression of EAE and increased mortality rates. Additionally, histological analysis showed that PLX3397 treatment significantly promoted inflammation, demyelination, and axonal degeneration. Moreover, the number of CD4+ T cells in the spinal cord of EAE mice was expanded due to PLX3397‐mediated proliferation. These results suggest that microglia suppressed secondary progression of EAE by inhibiting the proliferation of CD4+ T cells in the CNS.
Patterns of care and survival impact of adjuvant chemoradiotherapy for oropharyngeal cancer with intermediate‐risk features
Authors: Goel Alexander N. , Sangar Sophia , Mukdad Laith , Heaton Chase M. , Ryan William R. , Wang Marilene B. , Long Jennifer L. , St. John Maie A.
Published: May 2019

Background

Survival outcomes for adjuvant chemoradiotherapy (aCRT) and adjuvant radiotherapy (aRT) were compared in patients with oropharyngeal squamous cell carcinoma (OPSCC) with intermediate‐risk features.

Methods

We identified 2164 patients with OPSCC in the National Cancer Database without positive margins or extracapsular extension and with at least one intermediate‐risk feature: pT3‐T4 disease, ≥two positive lymph nodes, level IV/V nodal disease, and/or lymphovascular invasion. We assessed predictors of aCRT use and covariables impacting overall survival.

Results

aCRT was commonly used for both human papillomavirus (HPV)‐positive (62.0%) and HPV‐negative (64.3%) patients with OPSCC. Higher N stage, level IV/V neck disease, and younger age strongly predicted aCRT utilization. There was no significant survival benefit associated with aCRT vs aRT in HPV‐positive (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.62‐1.38; P = .71) or HPV‐negative (HR, 0.75; 95% CI, 0.51‐1.10; P = .15) disease.

Conclusions

Despite high rates of utilization, aCRT is not associated with better survival vs aRT for OPSCC with intermediate‐risk features, including HPV‐negative tumors.
Quality Measures, All‐Cause Mortality, and Health Care Use in a National Cohort of Veterans With Cirrhosis
Authors: Serper Marina , Kaplan David E. , Shults Justine , Reese Peter P. , Beste Lauren A. , Taddei Tamar H. , Werner Rachel M.
Published: May 2019

Decompensated cirrhosis is associated with high morbidity and mortality. However, no standardized quality measures (QMs) have yet been adopted widely. The Veterans Affairs (VA) Advanced Liver Disease Technical Advisory Group recently developed a set of six internal QMs to guide quality improvement efforts in cirrhosis in the domains of access to care, hepatocellular carcinoma surveillance, variceal surveillance, quality of inpatient care for upper gastrointestinal bleeding, and cirrhosis‐related rehospitalizations. We aimed to (1) quantify adherence to cirrhosis QMs and (2) determine whether adherence was associated with all‐cause mortality and health care use within a large national cohort of veterans with cirrhosis. We performed a retrospective study using data from the Veterans Outcomes and Costs Asociated with Liver Disease cohort of 121,129 patients newly diagnosed with cirrhosis from January 1, 2008, to December 31, 2016, at 128 VA facilities. The mean follow‐up time was 2.7 years (interquartile range, 1.1‐5.1 years). Adherence to outpatient access to specialty care was 71%, variceal surveillance was 32%, and early postdischarge care was 54%. In adjusted analyses, outpatient access to specialty care (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.78‐0.82), hepatocellular carcinoma surveillance (HR, 0.92; 95% CI, 0.90‐0.95), variceal surveillance (HR, 0.93; 95% CI, 0.89‐0.99), and early postdischarge care (HR, 0.57; 95% CI, 0.54‐0.60) were associated with lower all‐cause mortality. Readmissions after 30 days (HR, 1.53; 1.46‐1.60) and 90 days (HR, 1.88; 95% CI, 1.54‐1.70) were associated with higher all‐cause mortality. Higher adherence to QMs was also associated with lower inpatient health care use. Conclusion: Five of the six proposed VA cirrhosis QMs were measurable using existing data sources, associated with mortality and health care use, and may be used to guide future quality improvement efforts in cirrhosis.
Using sediment rating parameters to evaluate the changes in sediment transport regimes in the middle Yellow River basin, China
Authors: Zhang Shiyan , Chen Dong , Chen Li , Chen Xiaobing , He Li
Published: May 2019

This study analyses the changes in sediment transport regimes in the middle Yellow River basin (MYRB) using sediment rating parameters. Daily streamflow and suspended sediment concentration data were collected at 35 hydrological stations from the 1950s to 2016, which can be divided into three periods based on the type and intensity of human activities: the base stage before 1970, the restraining stage from 1971 to 1989, and the restoration stage after 2002. Data within each period were fitted by log‐linear sediment rating curves and the sediment rating parameters were utilized to analyse the spatial and temporal variations in sediment transport regimes. The results show that sediment rating parameters are indicative of sediment transport regimes. In the base stage and the restraining stage, the hydrological stations can be categorized into four groups based on their locations on the rating parameter plot. The stations with small drainage basins were characterized by the highest sediment transport regime, followed by those located in the coarse‐particle zone, the loess zone, and the mountainous/forest zone. In the restoration stage, the difference in sediment transport regimes between different geomorphic zones became less distinguishable than in previous stages. During the transition from the base stage to the restraining stage, sediment rating parameters showed no significant changes in sediment transport regimes in all four geomorphic groups. During the transition from the restraining stage to the restoration stage, significant changes were observed in the coarse‐particle zone and the mountain/forest zone, indicating that the revegetation programme and large reservoirs imposed a stronger influence on sediment transport regimes in these two zones than in the rest of the MYRB. This study provides theoretical support for evaluating sediment transport regimes with sediment rating parameters.
More options for adjuvant treatment of HER2‐positive breast cancer: How to choose wisely?
Authors: Trapani Dario , Rajasekar Arun K.A. , Mathew Aju
Published: May 2019

Human epidermal growth factor receptor 2‐positivity (HER2) has a prognostic and predictive role in breast cancer. Trastuzumab, an anti‐HER2 therapy, has a crucial role in a curative setting in Stage I, II and III breast cancer. In recent years, more anti‐HER2 agents have been tested in clinical trials. Newer dosing strategies and combination approaches give us a plethora of options to treat a patient with early‐stage and locally advanced breast cancer. It has led to the possibility of providing a risk‐adapted treatment for patients with HER2‐positive breast cancer. In order to reduce overtreatment and protect patients from adverse effects, a deescalation framework can be used in patients at lower risk for recurrence. Similarly, in those with greater risk for recurrence, escalation of therapy can be considered with the goal of achieving a cure. In this narrative review, we aim to provide a critical appraisal of the recent research findings in the management of early‐stage and locally advanced breast cancer.
Wnt/IL‐1β/IL‐8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5
Authors: Milosevic Vladan , Kopecka Joanna , Salaroglio Iris C. , Libener Roberta , Napoli Francesca , Izzo Stefania , Orecchia Sara , Ananthanarayanan Preeta , Bironzo Paolo , Grosso Federica , Tabbò Fabrizio , Comunanza Valentina , Alexa‐Stratulat Teodora , Bussolino Federico , Righi Luisella , Novello Silvia , Scagliotti Giorgio V. , Riganti Chiara
Published: May 2019

Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM‐initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness‐related pathways determine chemoresistance. Moreover, there are no predictive markers of IC‐associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness‐related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo‐sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5‐knocked‐out (KO) IC clones were resensitized to the drugs in vitro and in patient‐derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β‐catenin/c‐myc axis that also increased IL‐8 and IL‐1β production. IL‐8 and IL‐1β‐KO IC clones reduced the c‐myc‐driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5‐KO clones had lower IL‐8 and IL‐1β secretion, and c‐myc transcriptional activity, suggesting that either Wnt/GSK3β/β‐catenin and IL‐8/IL‐1β signaling drive c‐myc‐mediated transcription of ABCB5. ABCB5 correlated with lower time‐to‐progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first‐line chemotherapy in MPM patients.
Quantum Dots Based Photocatalytic Hydrogen Evolution
Authors: Fan Xiang‐Bing , Yu Shan , Hou Bo , Kim Jong Min
Published: May 2019

Photocatalytic production of hydrogen from water can directly convert solar energy into chemical energy storage, which has significant advantages and great promise. As an emerging photosensitizer, the efficiency of quantum dots (QDs) based artificial photosynthetic system have made breakthroughs. In this review, we will give a summary of the development of QDs based photocatalytic hydrogen evolution in these years. First, we highlight different types of hydrogen evolution catalyst combined with QDs; then we focus on the surface modification and heterostructure formation of QDs to improve the photocatalytic efficiency, respectively. In the end, we will propose some Cd‐free QDs and future development of photocatalytic hydrogen evolution.
Elevated BMP and Mechanical Signaling Through YAP1/RhoA Poises FOP Mesenchymal Progenitors for Osteogenesis
Authors: Stanley Alexandra , Heo Su-jin , Mauck Robert L , Mourkioti Foteini , Shore Eileen M
Published: May 2019

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by the formation of extraskeletal bone, or heterotopic ossification (HO), in soft connective tissues such as skeletal muscle. All familial and sporadic cases with a classic clinical presentation of FOP carry a gain-of-function mutation (R206H; c.617 G > A) in ACVR1, a cell surface receptor that mediates bone morphogenetic protein (BMP) signaling. The BMP signaling pathway is recognized for its chondro/osteogenic-induction potential, and HO in FOP patients forms ectopic but qualitatively normal endochondral bone tissue through misdirected cell fate decisions by tissue-resident mesenchymal stem cells. In addition to biochemical ligand-receptor signaling, mechanical cues from the physical environment are transduced to activate intracellular signaling, a process known as mechanotransduction, and can influence cell fates. Utilizing an established mesenchymal stem cell model of mouse embryonic fibroblasts (MEFs) from the Acvr1R206H/+ mouse model that mimics the human disease, we demonstrated that activation of the mechanotransductive effectors Rho/ROCK and YAP1 are increased in Acvr1R206H/+ cells. We show that on softer substrates, a condition associated with low mechanical signaling, the morphology of Acvr1R206H/+ cells is similar to the morphology of control Acvr1+/+ cells on stiffer substrates, a condition that activates mechanotransduction. We further determined that Acvr1R206H/+ cells are poised for osteogenic differentiation, expressing increased levels of chondro/osteogenic markers compared with Acvr1+/+ cells. We also identified increased YAP1 nuclear localization in Acvr1R206H/+ cells, which can be rescued by either BMP inhibition or Rho antagonism. Our results establish RhoA and YAP1 signaling as modulators of mechanotransduction in FOP and suggest that aberrant mechanical signals, combined with and as a result of the increased BMP pathway signaling through mutant ACVR1, lead to misinterpretation of the cellular microenvironment and a heightened sensitivity to mechanical stimuli that promotes commitment of Acvr1R206H/+ progenitor cells to chondro/osteogenic lineages.
Effect of microRNA‐27a‐5p on apoptosis and inflammatory response of pancreatic acinar cells in acute pancreatitis by targeting PTEN
Authors: Kong Lei , Wu Qinghua , Zhao Liangchao , Ye Jinhua , Li Nengping , Yang Huali
Published: May 2019

To investigate the apoptosis and inflammatory response of microRNA‐27a‐5p (miR‐27a‐5p) in pancreatic acinar cells of acute pancreatitis (AP) and its related mechanisms. Rat pancreatic acinar cell line AR42J was treated with caerulein (10nmol/L) to construct an acute pancreatitis cell model. Quantitative real‐time polymerase chain reaction was performed to measure the expression of miR‐27a‐5p; The miR‐27a‐5p mimic was transfected into cell, and the apoptosis rate of the cells was detected by flow cytometry; The levels of TNF‐α, IL‐1, and IL‐6 in the culture supernatant were determined by enzyme‐linked immunosorbent assay; TargetScans database predicted and dual luciferase reporter gene assay verified the relationship between miR‐27a‐5p and the phosphatase and tensin homolog deleted on chromosome 10 (PTEN); The recovery experiment explored the apoptosis and the effects of inflammatory responses. The expression of miR‐27a‐5p decreased gradually (P < 0.05) and the expression of PTEN increased gradually (P < 0.05) with the prolongation of acting time. Upregulation of miR‐27a‐5p significantly promoted cell apoptosis (P < 0.05) and inhibited inflammatory response (P < 0.05); The TargetScans database predicted that the 3'UTR of PTEN contains a base complementary to the miR‐27a‐5p seed region. Cotransfection of wild‐type vector (PTEN‐WT) with miR‐27a‐5p mimic or miR‐27a‐5p inhibitor significantly affected the relative activity of luciferase (P < 0.05), and no significant impact was observed in mutant PTEN‐MUT. Compared with miR‐27a‐5p + pcDNA group, transfection of miR‐27a‐5p mimic and pcDNA‐PTEN significantly increased the expression of PTEN (P < 0.05), decreased the apoptotic rate (P < 0.05), and increased the inflammatory response (P < 0.05). miR‐27a‐5p induced apoptosis and inhibited the inflammatory response of pancreatic acinar cells in AP by targeting PTEN.
Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel
Authors: Zhao Weijia , Chen Zonghan , Guan Meng
Published: May 2019

Despite improvements in the prognosis of osteosarcoma patients, chemotherapy fails in a considerable number of cases due to drug resistance. The development of novel agents may enhance chemosensitivity. This study explored the anticancer function of polydatin and its ability—in combination with paclitaxel—to overcome drug resistance in human osteosarcoma U‐2OS and MG‐63 cell lines. A cell proliferation assay (celll counting kit‐8), a cell‐cycle assay, an apoptosis assay (annexin V‐fluorescein isothiocyanate/propidium iodide), and a cell migration assay (Transwell) were used to analyze cell activity. Western blot analysis and quantitative reverse‐transcription polymerase chain reaction were performed to examine function‐related mRNA and protein levels. Treatment with polydatin suppressed cell growth and migration in both cell lines. Moreover, polydatin induced cell apoptosis in both parental and paclitaxel‐resistant cells, and cell‐cycle arrest in the S phase. Furthermore, it altered the expression of various proteins associated with cell growth (Ki67, p21, cyclin A, cyclin E, and cyclin‐dependent kinase 2), migration (matrix metalloproteinase‐2 [MMP‐2], MMP‐9, and tissue inhibitor of metalloproteinase‐1), apoptosis (poly[ADP‐ribose] polymerase 1 and caspase 3), and drug resistance (p‐glycoprotein 1, lung resistance‐related protein 1, growth arrest and DNA damage‐45α, glutathione S‐transferase π, and heat shock protein 27) in paclitaxel‐resistant osteosarcoma cells. Cells transfected with myr‐Akt caused obvious upregulation and activation of Akt, which were significantly attenuated via polydatin treatment. In conclusion, polydatin may enhance the chemosensitivity of osteosarcoma cells to paclitaxel.
Whole transcriptome analysis of diabetic nephropathy in the db/db mouse model of type 2 diabetes
Authors: Wen Li , Zhang Zheng , Peng Rui , Zhang Luyu , Liu Handeng , Peng Huimin , Sun Yan
Published: May 2019

Whole‐transcriptome analysis using RNA sequencing (RNA‐seq) affords broader insights about gene expression regulatory networks in diabetic nephropathy (DN). To better explore the molecular basis of DN, kidney tissue from db/db DN model mice and control mice were submitted to RNA‐seq analysis. Thousands of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) were found to be significantly differentially expressed in the DN group relative to the control group. To research the regulatory mechanism of these lncRNAs and mRNAs, the integrated co‐expression networks were constructed for 322 mRNAs and 27 lncRNAs that revealed significantly correlated expression patterns in DN. The potential roles of these co‐expressed mRNAs were classified by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The co‐expression networks involved 27 lncRNAs interacting with 38 key mRNAs related to metabolic processes, including ND4/4L, Ndufa2/5, Ndufb4/7, Ndufs3, Uqcrc1, Aco2, Alad, Alas1, Alpl, Atp5j2, Coq5, Coq6, Cth, and CytB, all of which are highly related to encoding subunits of the mitochondrial complexes. Thus, mitochondrial dysfunction could result in renal function decline in DN. Seven dysregulated lncRNAs and nine dysregulated mRNAs in the DN model were confirmed by quantitative real‐time polymerase chain reaction. The lncRNA‐mRNA co‐expression network provides novel evidence to support the contention that metabolic changes are associated with metabolic reprogramming in the kidneys, and that these changes play a critical role during the progression of DN.
Silencing microRNA‐221/222 cluster suppresses glioblastoma angiogenesis by suppressor of cytokine signaling‐3‐dependent JAK/STAT pathway
Authors: Xu Chun‐Hua , Liu Yue , Xiao Li‐Min , Chen Li‐Ke , Zheng Su‐Yue , Zeng Er‐Ming , Li Dong‐Hai , Li You‐Ping
Published: May 2019

Angiogenesis is a major pathologic characteristic of glioblastoma, which is one aggressive primary brain tumor. MicroRNA‐221/222 (miR‐221/222) cluster has been previously reported to function importantly in malignant glioma biological process. The current study aims at evaluating the effects of miR‐221/222 cluster on angiogenesis of glioblastoma cells. Microarray data were analyzed to select glioblastoma‐associated differentially expressed genes, and dual‐luciferase reporter assay was performed to assess targeting correlation between miR‐221/222 cluster and suppressor of cytokine signaling‐3 (SOCS3). Subsequently, the expression patterns of miR‐221 and miR‐222 in glioblastoma cells were identified. miR‐221 and miR‐222 were overexpressed or silenced in glioblastoma cells to identify the effect of miR‐221/222 cluster in cell invasion, migration, proliferation, and angiogenesis. To define downstream pathway of miR‐221/222 cluster or SOCS3 in glioblastoma, levels of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway‐related proteins were assessed. Additionally, the functions of miR‐221/222 on glioblastoma cell angiogenesis were measured in vivo with microvessel density assayed. miR‐221 and miR‐222 were expressed at a high level and SOCS3 was at a low level in glioblastoma. Downregulation of the miR‐221/222 cluster diminished the invasion, migration, proliferation, and angiogenesis with reduced protein levels of matrix metalloproteinase‐2 (MMP‐2), MMP‐9, and vascular endothelial growth factor in glioblastoma cells. Also, silencing miR‐221/222 cluster reduced p‐JAK2/JAK2 and p‐STAT3/STAT3. Consistently, the inhibitory role of silencing miR‐221/222 cluster on tumorigenesis of glioblastoma cells was confirmed in vivo. Collectively, the inhibition of miR‐221/222 cluster could attenuate the glioblastoma angiogenesis through inactivation of the JAK/STAT pathway by upregulating SOCS3.