bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards Imaging Pt Chemoresistance Using Gd(III)‐Pt(II) Theranostic MR Contrast Agents
Authors: Adams Casey J. , Meade Thomas J. 
Published: August 2021

AbstractCisplatin and related Pt(II) chemotherapeutics are indispensable tools for the treatment of various solid tumors. Despite their widespread clinical use in approximately 50 % of chemotherapy regimens, they are hindered by issues with off‐target toxicity and chemoresistance, both innate and acquired. To date, there is no effective way to predict the outcome of Pt(II) chemotherapy because the genes associated with resistance are not completely known or understood. Instead, patients undergo weeks to months of potentially harmful therapy before knowing if it is effective. Here we report two Gd(III)‐Pt(II) theranostic MR contrast agents that contain cisplatin and carboplatin‐based moieties respectively. We used these agents to demonstrate that accumulation differences in Pt(II) sensitive and resistant cells, a dominant factor in chemoresistance, can be imaged by MR. Both theranostic agents bind to DNA, are cytotoxic, and enhance the intracellular T1‐weighted MR contrast of multiple cell lines. Most importantly, the cisplatin‐based agent accumulates less in Pt(II) resistant cells in vitro and in vivo, resulting in decreased MR contrast enhancement compared to the parent Pt(II) sensitive cell line. This straightforward method to image a key factor of Pt(II) resistance using MRI is an important first step towards the ultimate goals of predicting response to Pt(II) chemotherapy and monitoring for the onset of chemoresistance – a critical unmet need in medicine that could significantly improve patient outcomes.
Direct, Late‐Stage Mono‐N‐arylation of Pentamidine: Method Development, Mechanistic Insight, and Expedient Access to Novel Antiparastitics against Diamidine‐Resistant Parasites
Authors: Robertson Jack , Ungogo Marzuq A. , Aldfer Mustafa M. , Lemgruber Leandro , McWhinnie Fergus S. , Bode Bela E. , Jones Katherine L. , Watson Allan J. B. , de Koning Harry P. , Burley Glenn A. 
Published: August 2021

AbstractA selective mono‐N‐arylation strategy of amidines under Chan‐Lam conditions is described. During the reaction optimization phase, the isolation of a mononuclear Cu(II) complex provided unique mechanistic insight into the operation of Chan‐Lam mono‐N‐arylation. The scope of the process is demonstrated, and then applied to access the first mono‐N‐arylated analogues of pentamidine. Sub‐micromolar activity against kinetoplastid parasites was observed for several analogues with no cross‐resistance in pentamidine and diminazene‐resistant trypanosome strains and against Leishmania mexicana. A fluorescent mono‐N‐arylated pentamidine analogue revealed rapid cellular uptake, accumulating in parasite nuclei and the kinetoplasts. The DNA binding capability of the mono‐N‐arylated pentamidine series was confirmed by UV‐melt measurements using AT‐rich DNA. This work highlights the potential to use Chan‐Lam mono‐N‐arylation to develop therapeutic leads against diamidine‐resistant trypanosomiasis and leishmaniasis.
Determinants of patient‐reported xerostomia among long‐term oropharyngeal cancer survivors
Authors: Aggarwal Puja , Hutcheson Katherine A. , Garden Adam S. , Mott Frank E. , Lu Charles , Goepfert Ryan P. , Fuller Clifton D. , Lai Stephen Y. , Gunn G. Brandon , Chambers Mark S. , Sturgis Erich M. , Hanna Ehab Y. , Shete Sanjay 
Published: August 2021

BackgroundThis study was conducted to identify clinicodemographic risk factors for xerostomia among long‐term oropharyngeal cancer (OPC) survivors.MethodsThis cross‐sectional study included 906 disease‐free, adult OPC survivors with a median survival duration at the time of survey of 6 years (range, 1‐16 years); self‐reported xerostomia scores were available for 877 participants. Study participants had completed curative treatment between January 2000 and December 2013 and responded to a survey administered from September 2015 to July 2016. The primary outcome variable was cancer patient–reported xerostomia measured with the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified via multivariable logistic regression.ResultsModerate to severe xerostomia was reported by 343 of the respondents (39.1%). Female sex (odds ratio [OR], 1.82; 95% CI, 1.22‐2.71; P = .003; Bayesian false‐discovery probability [BFDP] = 0.568), high school or lower education (OR, 1.73; 95% CI, 1.19‐2.52; P = .004; BFDP = 0.636), and current cigarette smoking at the time of survey (OR, 2.56; 95% CI, 1.19‐5.47; P = .016; BFDP = 0.800) were risk factors for moderate to severe xerostomia, and bilateral intensity‐modulated radiotherapy (IMRT) combined with proton therapy and ipsilateral IMRT were protective.ConclusionsIn this large xerostomia study, modern radiotherapy was a protective factor, and continued cigarette smoking at the time of survey, female sex, and high school or lower education were identified as other contributing risk factors associated with moderate to severe xerostomia. Importantly, these findings need to be confirmed in prospective studies. These results can inform future research and targeted patient‐centered interventions to monitor and manage radiation therapy–associated xerostomia and preserve quality of life among patients with OPC.
Spectral spatial joint feature based convolution neural network for hyperspectral image classification
Authors: Kumar Pathak Diganta , Kumar Kalita Sanjib , Kumar Bhattacharya Dhruba 
Published: August 2021

AbstractHyperspectral sensor generates huge datasets which conveys abundance of information. However, it poses many challenges in the analysis and interpretation of these data. Deep networks like VGG16, VGG19 are difficult to directly apply for hyperspectral image (HSI) classification because of its higher number of layers which in turn requires high level of system resources. This article suggests a novel framework with lesser number of layers for hyperspectral image classification (HSIC) that takes into account spectral‐spatial context sensitivity of HSI, which focuses on enhancing the discriminating capability of HSIC. The model uses available spectral feature as well as spatial contexts of HSI and consecutively learn the distinctive features. A small training set has been used to optimize the network parameters while the overfitting problem is alleviated using the validation set. Regularization has been performed using batch normalization (BN) layer after each convolution layer. The cost of the model is measured in terms of training and testing time duration under the same platform, which has further been compared with some ensemble learning methods, SVM and other three recent state‐of‐the‐art methods. Experimental results establish that the proposed model performs very well with the three benchmark datasets: Indian Pines, Salinas and University of Pavia, which mostly contain land cover of agriculture, forest, soil, rural, and urban area.
Early Divergence in Misfolding Pathways of Amyloid‐Beta Peptides
Authors: Mamone Salvatore , Glöggler Stefan , Becker Stefan , Rezaei‐Ghaleh Nasrollah 
Published: August 2021

AbstractThe amyloid cascade hypothesis proposes that amyloid‐beta (Aβ) aggregation is the initial triggering event in Alzheimer's disease. Here, we utilize NMR spectroscopy and monitor the structural dynamics of two variants of Aβ, Aβ40 and Aβ42, as a function of temperature. Despite having identical amino acid sequence except for the two additional C‐terminal residues, Aβ42 has higher aggregation propensity than Aβ40. As revealed by the NMR data on dynamics, including backbone chemical shifts, intra‐methyl cross‐correlated relaxation rates and glycine‐based singlet‐states, the C‐terminal region of Aβ, especially the G33‐L34‐M35 segment, plays a particular role in the early steps of temperature‐induced Aβ aggregation. In Aβ42, the distinct dynamical behaviour of C‐terminal residues at higher temperatures is accompanied with marked changes in the backbone dynamics of residues V24‐K28. The distinctive role of the C‐terminal region of Aβ42 in the initiation of aggregation defines a target for the rational design of Aβ42 aggregation inhibitors.
Historical biogeography of the genusRhadinaea(Squamata: Dipsadinae)
Authors: García‐Sotelo Uriel A. , García‐Vázquez Uri O. , Espinosa David 
Published: August 2021

AbstractMultiple geological and climatic events have created geographical or ecological barriers associated with speciation events, playing a role in biological diversification in North and Central America. Here, we evaluate the influence of the Neogene and Quaternary geological events, as well as the climatic changes in the diversification of the colubrid snake genusRhadinaeausing molecular dating and ancestral area reconstruction. A multilocus sequence dataset was generated for 37 individuals ofRhadinaeafrom most of the biogeographical provinces where the genus is distributed, representing 19 of the 21 currently recognized species, and two undescribed species. Our analyses show that the majority of theRhadinaeaspecies nest in two main clades, herein identified as “Eastern” and “Southern”. These clades probably diverged from each other in the early Miocene, and their divergence was followed by 11 divergences during the middle to late Miocene, three divergences during the Pliocene, and six divergences in the Pleistocene. The ancestral distribution ofRhadinaeawas reconstructed across the Sierra Madre del Sur. Our phylogenetic analyses do not support the monophyly ofRhadinaea. The Miocene and Pliocene geomorphology, perhaps in conjunction with climate change, appears to have triggered the diversification of the genus, while the climatic changes during the Miocene probably induced the diversification ofRhadinaeain the Sierra Madre del Sur. Our analysis suggests that the uplifting of the Trans‐Mexican Volcanic Belt and Chiapan–Guatemalan highlands in this same period resulted in northward and southward colonization events. This was followed by more recent, independent colonization events in the Pliocene and Pleistocene involving the Balsas Basin, Chihuahuan Desert, Pacific Coast, Sierra Madre Occidental, Sierra Madre Oriental, Sierra Madre del Sur, Trans‐Mexican Volcanic Belt, and Veracruz provinces, probably driven by the climatic fluctuations of the time.
The cost of evolved constitutive lac gene expression is usually, but not always, maintained during evolution of generalist populations
Authors: Phillips Kelly N. , Cooper Tim F. 
Published: August 2021

AbstractBeneficial mutations can become costly following an environmental change. Compensatory mutations can relieve these costs, while not affecting the selected function, so that the benefits are retained if the environment shifts back to be similar to the one in which the beneficial mutation was originally selected. Compensatory mutations have been extensively studied in the context of antibiotic resistance, responses to specific genetic perturbations, and in the determination of interacting gene network components. Few studies have focused on the role of compensatory mutations during more general adaptation, especially as the result of selection in fluctuating environments where adaptations to different environment components may often involve trade‐offs. We examine whether costs of a mutation in lacI, which deregulated the expression of the lac operon in evolving populations of Escherichia coli bacteria, were compensated. This mutation occurred in multiple replicate populations selected in environments that fluctuated between growth on lactose, where the mutation was beneficial, and on glucose, where it was deleterious. We found that compensation for the cost of the lacI mutation was rare, but, when it did occur, it did not negatively affect the selected benefit. Compensation was not more likely to occur in a particular evolution environment. Compensation has the potential to remove pleiotropic costs of adaptation, but its rarity indicates that the circumstances to bring about the phenomenon may be peculiar to each individual or impeded by other selected mutations.
Weighing the predictors: host traits and coinfecting species both explain variation in parasitism of Rock Ptarmigan
Authors: Morrill André , Nielsen Ó. K. , Stenkewitz U. , Pálsdóttir G. R. , Forbes M. R. , Skírnisson K. 
Published: August 2021

AbstractTesting hypotheses in ecological and evolutionary parasitology can require testing whether host traits or coinfecting parasites explain variation in parasitism by focal species. However, when host traits and coinfecting parasites are considered separately, relations between either and parasitism by focal species can be spurious—a problem that is addressed when both are considered together. We assessed whether abundances of focal parasites related to host age/sex and coinfecting parasites for three endoparasites and nine ectoparasites of Icelandic Rock Ptarmigan (Lagopus muta) collected over 12 yr (2006–2017), and quantified the variation in focal parasitism explained by these predictors. Host traits and coinfecting parasites explained significant variation in abundance of all nine focal parasite species for which models converged, when those models were based on groups of parasites sharing tissue tropism and/or transmission pathways and included year as a random effect. We found a single spurious relation: a host age–sex interaction effect that was removed once concurrent parasitism was considered. When considering focal parasites within groups of coinfecting parasites, we found cases of positive, negative, and lacks of correlations. The amount of variation in focal parasite abundance explained by host traits versus coinfecting parasites depended on the focal parasite and its group. Overall variation explained was both related to the prevalence of the focal parasite, possibly due to underlying parasite aggregation, and similar to variation explained in other models in ecology and evolution. We conclude that host traits and coinfecting parasites often combine to determine infection by focal species. Future studies should also explore the mechanisms underlying parasite–parasite relations and their potential impacts on host demography for this and other study associations, and assess relative effects of host traits and coinfecting parasites on focal parasitism.
[11C]HCN Radiochemistry: Recent Progress and Future Perspectives
Authors: Xu Youwen , Qu Wenchao 
Published: August 2021

AbstractPositron emission tomography (PET) is a unique non‐invasive imaging tool for studying in vivo biological processes. It utilizes short‐lived positron emitter labeled organic molecules to study biological events in real‐time. To incorporate the positron emitter into a molecule of biological interest, radioactive synthons are developed to facilitate radiolabeling chemistry. In addition to 11C‐methylation with [11C]CH3I/[11C]CH3OTf, 11C‐carbonylation with [11C]CO, and 11C‐carboxylation of organometallic reagents with [11C]CO2, 11C‐cyanation with [11C]HCN is another frequently used 11C‐labeling methodology. It can lead to the generation of [11C]organo‐nitriles, [carbonyl‐11C]carboxylic acids, [carbonyl‐11C]aldehydes, [carbonyl‐11C]amides, [11C]alkyl amines, [tetrazoyl‐11C]tetrazoles, [11C]CN‐containing heterocycles, etc. This review recognizes the important roles of 11C‐cyanation reactions with the emphasis of recent advances, along with the discussion of molar activities (Am) of [11C]HCN based radiotracers and prompts for future potential [11C]cyanide based radiotracer development.
DTBP‐Mediated Cascade Spirocyclization and Dearomatization of Biaryl Ynones: Facile Access to Spiro[5.5]trienones through C(sp3)−H Bond Functionalization
Authors: Zhang Ming‐Ming , Shen Liu‐Yu , Dong Sa , Li Bing , Meng Fei , Si Wei‐Jie , Yang Wen‐Chao 
Published: August 2021

AbstractOxidative radical cascade spirocyclization and dearomatization of biary ynones with a variety of hydrocarbons including toluenes, ethers, ketones, and alkanes has been developed to construct alkyl substituted spiro[5.5]trienones.
Segmentation‐based analysis of single‐cell immunoblots
Authors: Gopal Anjali , Herr Amy E. 
Published: August 2021

AbstractFrom genomics to transcriptomics to proteomics, microfluidic tools underpin recent advances in single‐cell biology. Detection of specific proteoforms—with single‐cell resolution—presents challenges in detection specificity and sensitivity. Miniaturization of protein immunoblots to single‐cell resolution mitigates these challenges. For example, in microfluidic western blotting, protein targets are separated by electrophoresis and subsequently detected using fluorescently labeled antibody probes. To quantify the expression level of each protein target, the fluorescent protein bands are fit to Gaussians; yet, this method is difficult to use with noisy, low‐abundance, or low‐SNR protein bands, and with significant band skew or dispersion. In this study, we investigate segmentation‐based approaches to robustly quantify protein bands from single‐cell protein immunoblots. As compared to a Gaussian fitting pipeline, the segmentation pipeline detects >1.5× more protein bands for downstream quantification as well as more of the low‐abundance protein bands (i.e., with SNR ∼3). Utilizing deep learning‐based segmentation approaches increases the recovery of low‐SNR protein bands by an additional 50%. However, we find that segmentation‐based approaches are less robust at quantifying poorly resolved protein bands (separation resolution, Rs < 0.6). With burgeoning needs for more single‐cell protein analysis tools, we see microfluidic separations as benefitting substantially from segmentation‐based analysis approaches.
Elucidating active sites and decomposition mechanisms for oxythiomolybdate clusters (Mo2O2Sx, x = 6;8) as catalyzers for hydrogen evolution reactions
Authors: Bertolini Samuel , Jacob Timo 
Published: August 2021

AbstractWe investigated the decomposition mechanism of Mo3S13 (chalcogenides) and Mo2O2Sx(x = 6,8) through Density Functional Theory, in particular Mo2O2Sx. Oxythiomolybdates are more stable than chalcogenides, and decompose through cathodic reactions, while chalcogenides decompose also through anodic reactions. The solvent acts on the polymerization mechanism of Mo2O2S6, blocking or reducing the polymerization between Mo2O2S6 clusters. The electrons’ excess is responsible for the catalyst decomposition and, also induces absorption of hydrogen on terminal oxygen. Moreover, Mo2O2S6 absorbs two hydrogens on each terminal disulfide without absorbing electrons. The Mo2O2S4 can absorb one hydrogen and catalyze hydrogen evolution reactions (HER), however, decomposition still occurs. Ab initio molecular dynamics shows the explicit absorption of hydrogen in Mo2O2S6 by adding electrons to the system, in which hydrogen can be absorbed in a disulfide or in an oxygen terminal. Heyrovsky mechanism tends to dominate HER, and hydrogen absorption can also remove oxygen from Mo2O2S6 and produce water.
Formic acid reduction and CO2 activation at Mo2C: The important role of surface oxide
Authors: Winkler Daniel , Dietrich Valentin , Griesser Christoph , Nia Niusha Shakibi , Wernig Eva‐Maria , Tollinger Martin , Kunze‐Liebhäuser Julia 
Published: August 2021

AbstractSmall organic acids, such as formic or acetic acid, which are well‐known products of the electrochemical CO2 reduction reaction, are often not further reduceable to their respective alcohols. Alcohols are well‐desired chemicals and useful as fuels, since they can be easily purified and provide a high energy density. Here, we present a combined electrochemical, differential electrochemical mass spectrometry (DEMS), and nuclear magnetic resonance spectroscopy (NMR) study, providing insight in the electro‐reduction of formic acid on Mo2C electrodes, and the corresponding formation of notable amounts of methanol, with a Faraday efficiency of ∼27 % at a high steady state current density of –0.3 mA/cm2 compared to other formic acid electroreduction catalysts, such as Pb or Sn. Intriguingly, we find that formic and acetic acid readily form on native oxide covered Mo2C surfaces in air and especially in humid CO2 atmosphere. We realize that the thin native oxide layer that is ubiquitously present on these electrodes is the key factor for the activation of CO2 and the corresponding formation of formic and acetic acid at the solid/gas interface. Subsequent electrochemical reduction of these two acids at the solid/liquid interface proceeds through direct formation of their respective alcohols. The activity toward organic acid reduction on Mo2C catalysts can therefore be enhanced by their adsorption properties at the surface and not necessarily through inhibition of the HER, which is exceptional and points to a general strength of compound catalysts for organic acid reduction and CO2 activation.
A review on binder‐free NiO‐Ni foam as anode of high performance lithium‐ion batteries
Authors: Rahman Md. Arafat , Rahman Md. Mizanur , Song Guangsheng 
Published: August 2021

AbstractIn recent times, lithium‐ion batteries (LIBs) are widely used in the fields of small electronic devices, wearable electronic devices, and automobiles. In the light of some current research on LIBs investigated on replacing commercial carbonaceous anode materials with transition metal oxides such as NiO due to its high theoretical capacity of 718 mAh g−1. However, NiO still suffers from low cycling stability, low coulombic efficiency, and low rate capability resulting from large volume expansion and poor electrical conductivity which greatly limits the development of large‐capacity LIBs. To overcome these barriers, various NiO electrodes with different morphologies and physical structures are developed. In this review, we introduce and summarize the electrochemical performances of binder‐free NiO‐Ni foam as anode of LIBs.
Kudzu isoflavone C‐glycosides: Analysis, biological activities, and metabolism
Authors: Prasain Jeevan K. , Barnes Stephen , Wyss J. Michael 
Published: August 2021

AbstractRadix Pueraria (the root of kudzu Pueraria lobota) is a popular traditional Chinese medicine used in dietary supplements in Western markets and has potential health benefits. Kudzu roots are rich in isoflavones C‐ and O‐glycosides, of which puerarin (daidzein 8‐C‐glucoside) is the most abundant isoflavone. Puerarin is a unique isoflavone that it is resistant to intestinal hydrolysis and has a wide range of effects in preventing metabolic diseases. Our previous studies indicate that chronic exposure to a diet enriched in puerarin significantly reduces serum total cholesterol, arterial blood pressure, insulin resistance and hyperglycemia in ovariectomized, stroke‐prone spontaneously hypertensive rats (SP‐SHR), a model of metabolic syndrome. Further, our studies demonstrate that puerarin is absorbed as the intact glucoside and acutely improves glucose tolerance, indicating that it has potential for the prevention and treatment of diabetes. This paper reviews recent progress in the understanding of biological activities and metabolism and in the analysis of puerarin in kudzu root extracts or supplements.