bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small‐Molecule Inhibitors of Shp2 Phosphatase as Potential Chemotherapeutic Agents for Glioblastoma: A Minireview
Authors: Mitra Rangan , Ayyannan Senthil R. 
Published: November 2020

AbstractGlioblastoma multiforme (GBM) is a dreadful cancer characterised by poor prognosis, low survival rate and difficult clinical correlations. Several signalling pathways and molecular mediators are known to precipitate GBM, and small‐molecular targets of these mediators have become a favoured thrust area for researchers to develop potent anti‐GBM drugs. Shp2, an important phosphatase of the nonreceptor type protein tyrosine phosphatase (PTPN) subfamily is responsible for master regulation of several such signalling pathways in normal and glioma cells. Thus, inhibition of Shp2 is a logical strategy for the design and development of anti‐neoplastic drugs against GBM. Though tapping the full potential of Shp2 binding sites has been challenging, nevertheless, many synthetic and natural scaffolds have been documented as possessing potent and selective anti‐Shp2 activities in biochemical and cellular assays, through either active‐site or allosteric binding. Most of these scaffolds share a few common pharmacophoric features, a thorough study of which is useful in paving the way for the design and development of improved Shp2 inhibitors. This minireview summarizes the current scenario of potent small‐molecule Shp2 inhibitors and emphasizes the anti‐GBM potential of some important scaffolds that have shown promising GBM‐specific activity in in vitro and in vivo models, thus proving their efficacy in GBM therapy. This review could guide researchers to design new and improved anti‐Shp2 pharmacophores and develop them as anti‐GBM agents by employing GBM‐centric drug‐discovery protocols.
Bioengineering of Anti‐Inflammatory Natural Products
Authors: Winand Lea , Sester Angela , Nett Markus 
Published: November 2020

AbstractInflammatory processes occur as a generic response of the immune system and can be triggered by various factors, such as infection with pathogenic microorganisms or damaged tissue. Due to the complexity of the inflammation process and its role in common diseases like asthma, cancer, skin disorders or Alzheimer's disease, anti‐inflammatory drugs are of high pharmaceutical interest. Nature is a rich source for compounds with anti‐inflammatory properties. Several studies have focused on the structural optimization of natural products to improve their pharmacological properties. As derivatization through total synthesis is often laborious with low yields and limited stereoselectivity, the use of biosynthetic, enzyme‐driven reactions is an attractive alternative for synthesizing and modifying complex bioactive molecules. In this minireview, we present an outline of the biotechnological methods used to derivatize anti‐inflammatory natural products, including precursor‐directed biosynthesis, mutasynthesis, combinatorial biosynthesis, as well as whole‐cell and in vitro biotransformation.
Photophysics of Fluorescent Contact Sensors Based on the Dicyanodihydrofuran Motif
Authors: Suhina Tomislav , Bonn Daniel , Weber Bart , Brouwer Albert M. 
Published: November 2020

AbstractFluorescent molecular rotors have been used for measurements of local mobility on molecular length scales, for example to determine viscosity, and for the visualization of contact between two surfaces. In the present work, we deepen our insight into the excited‐state deactivation kinetics and mechanics of dicyanodihydrofuran‐based molecular rotors. We extend the scope of the use of this class of rotors for contact sensing with a red‐shifted member of the family. This allows for contact detection with a range of excitation wavelengths up to ∼600 nm. Steady‐state fluorescence shows that the fluorescence quantum yield of these rotors depends not only on the rigidity of their environment, but – under certain conditions – also on its polarity. While excited state decay via rotation about the exocyclic double bond is rapid in nonpolar solvents and twisting of a single bond allows for fast decay in polar solvents, the barriers for both processes are significant in solvents of intermediate polarity. This effect may also occur in other molecular rotors, and it should be considered when applying such molecules as local mobility probes.
COVIDOSE: A Phase II Clinical Trial of Low‐Dose Tocilizumab in the Treatment of Noncritical COVID‐19 Pneumonia
Authors: Strohbehn Garth W. , Heiss Brian L. , Rouhani Sherin J. , Trujillo Jonathan A. , Yu Jovian , Kacew Alec J. , Higgs Emily F. , Bloodworth Jeffrey C. , Cabanov Alexandra , Wright Rachel C. , Koziol Adriana K. , Weiss Alexandra , Danahey Keith , Karrison Theodore G. , Edens Cuoghi C. , Bauer Ventura Iazsmin , Pettit Natasha N. , Patel Bhakti K. , Pisano Jennifer , Strek Mary E. , Gajewski Thomas F. , Ratain Mark J. , Reid Pankti D. 
Published: November 2020

Interleukin‐6 (IL‐6)–mediated hyperinflammation may contribute to the mortality of coronavirus disease 2019 (COVID‐19). The IL‐6 receptor–blocking monoclonal antibody tocilizumab has been repurposed for COVID‐19, but prospective trials and dose‐finding studies in COVID‐19 have not yet fully reported. We conducted a single‐arm phase II trial of low‐dose tocilizumab in nonintubated hospitalized adult patients with COVID‐19, radiographic pulmonary infiltrate, fever, and C‐reactive protein (CRP) ≥ 40 mg/L. We hypothesized that doses significantly lower than the emerging standards of 400 mg or 8 mg/kg would resolve clinical and laboratory indicators of hyperinflammation. A dose range from 40 to 200 mg was evaluated, with allowance for one repeat dose at 24 to 48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Thirty‐two patients received low‐dose tocilizumab, with the majority experiencing fever resolution (75%) and CRP decline consistent with IL‐6 pathway abrogation (86%) in the 24–48 hours following drug administration. There was no evidence of a relationship between dose and fever resolution or CRP decline over the dose range of 40–200 mg. Within the 28‐day follow‐up, 5 (16%) patients died. For patients who recovered, median time to clinical recovery was 3 days (interquartile range, 2–5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (16%) patients. Low‐dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with COVID‐19. Results of this trial provide rationale for a randomized, controlled trial of low‐dose tocilizumab in COVID‐19.
Antibacterial effect of nanocurcumin inside the implant fixture: An in vitro study
Authors: Negahdari Ramin , Ghavimi Mohammad Ali , Barzegar Ali , Memar Mohammad Yousef , Balazadeh Ladan , Bohlouli Sepideh , Sharifi Simin , Maleki Dizaj Solmaz 
Published: November 2020

AbstractObjectivesInfections after implant placement are the main reasons for the failure of implant treatments. The present study aimed to evaluate the antibacterial effects of nanocurcumin inside the implant fixture against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis.Materials and MethodsTwenty seven implants were classified in three groups for testing the antibacterial effect of nanocurcumin, chlorhexidine (as negative control), and distilled water (as negative control). Each group was then divided into three subgroups to study the effect of the applied torque on the antimicrobial effect of nanocurcumin. All implant abutment assemblies were submerged in bacteria suspension and were incubated at 37°C for 24 hours. The contents of each implant were removed to count the colony of bacteria on the surface of plates containing nutrient agar.ResultsResults indicated that the inhibitory rate of bacteria by nanocurcumin was above 99% in all bacteria. Besides, by increasing the amount of applied torque from 10 to 35 N.cm, the CFU of bacteria in exposure to nanocurcumin significantly were decreased (p‐value < 0.01).ConclusionThe results of this study revealed that nanocurcumin can be used inside the implant fixture in order to use antimicrobial effects and further stabilization and success of the implant.
A multispecies approach to manage effects of land cover and weather on upland game birds
Authors: Schindler Alexander R. , Haukos David A. , Hagen Christian A. , Ross Beth E. 
Published: November 2020

AbstractLoss and degradation of grasslands in the Great Plains region have resulted in major declines in abundance of grassland bird species. To ensure future viability of grassland bird populations, it is crucial to evaluate specific effects of environmental factors among species to determine drivers of population decline and develop effective conservation strategies. We used threshold models to quantify the effects of land cover and weather changes in "lesser prairie‐chicken" and "greater prairie‐chicken" (Tympanuchus pallidicinctus and T. cupido, respectively), northern bobwhites (Colinus virginianus), and ring‐necked pheasants (Phasianus colchicus). We demonstrated a novel approach for estimating landscape conditions needed to optimize abundance across multiple species at a variety of spatial scales. Abundance of all four species was highest following wet summers and dry winters. Prairie chicken and ring‐necked pheasant abundance was highest following cool winters, while northern bobwhite abundance was highest following warm winters. Greater prairie chicken and northern bobwhite abundance was also highest following cooler summers. Optimal abundance of each species occurred in landscapes that represented a grassland and cropland mosaic, though prairie chicken abundance was optimized in landscapes with more grassland and less edge habitat than northern bobwhites and ring‐necked pheasants. Because these effects differed among species, managing for an optimal landscape for multiple species may not be the optimal scenario for any one species.
Genetic structure and life history are key factors in species distribution models of spiny lobsters
Authors: Singh Sohana P. , Groeneveld Johan C. , Willows‐Munro Sandi 
Published: November 2020

AbstractAimWe incorporated genetic structure and life history phase in species distribution models (SDMs) constructed for a widespread spiny lobster, to reveal local adaptations specific to individual subspecies and predict future range shifts under the RCP 8.5 climate change scenario.LocationIndo‐West Pacific.MethodsMaxEnt was used to construct present‐day SDMs for the spiny lobster Panulirus homarus and individually for the three genetically distinct subspecies of which it comprises. SDMs incorporated both sea surface and benthic (seafloor) climate layers to recreate discrete influences of these habitats during the drifting larval and benthic juvenile and adult life history phases. Principle component analysis (PCA) was used to infer environmental variables to which individual subspecies were adapted. SDM projections of present‐day habitat suitability were compared with predictions for the year 2,100, under the RCP 8.5 climate change scenario.ResultsIn the PCA, salinity best explained P. h. megasculptus habitat suitability, compared with current velocity in P. h. rubellus and sea surface temperature in P. h. homarus. Drifting and benthic life history phases were adapted to different combinations of sea surface and benthic environmental variables considered. Highly suitable habitats for benthic phases were spatially enveloped within more extensive sea surface habitats suitable for drifting larvae. SDMs predicted that present‐day highly suitable habitats for P. homarus will decrease by the year 2,100.Main conclusionsIncorporating genetic structure in SDMs showed that individual spiny lobster subspecies had unique adaptations, which could not be resolved in species‐level models. The use of sea surface and benthic climate layers revealed the relative importance of environmental variables during drifting and benthic life history phases. SDMs that included genetic structure and life history were more informative in predictive models of climate change effects.
Morning glory species co-occurrence is associated with asymmetrically decreased and cascading reproductive isolation
Authors: Ostevik Kate L. , Rifkin Joanna L. , Xia Hanhan , Rausher Mark D 
Published: November 2020

AbstractHybridization between species can affect the strength of the reproductive barriers that separate those species. Two extensions of this effect are (1) the expectation that asymmetric hybridization or gene flow will have asymmetric effects on reproductive barrier strength and (2) the expectation that local hybridization will affect only local reproductive barrier strength and could therefore alter within-species compatibility. We tested these hypotheses in a pair of morning glory species that exhibit asymmetric gene flow from highly selfing Ipomoea lacunosa into mixed-mating Ipomoea cordatotriloba in regions where they co-occur. Because of the direction of this gene flow, we predicted that reproductive barrier strength would be more strongly affected in I. cordatotriloba than I. lacunosa. We also predicted that changes to reproductive barriers in sympatric I. cordatotriloba populations would affect compatibility with allopatric populations of that species. We tested these predictions by measuring the strength of a reproductive barrier to seed set across the species’ ranges. Consistent with our first prediction, we found that sympatric and allopatric I. lacunosa produce the same number of seeds in crosses with I. cordatotriloba, whereas crosses between sympatric I. cordatotriloba and I. lacunosa are more successful than crosses between allopatric I. cordatotriloba and I. lacunosa. This difference in compatibility appears to reflect an asymmetric decrease in the strength of the barrier to seed set in sympatric I. cordatotriloba, which could be caused by I. lacunosa alleles that have introgressed into I. cordatotriloba. We further demonstrated that changes to sympatric I. cordatotriloba have decreased its ability to produce seeds with allopatric populations of the same species, in line with our second prediction. Thus, in a manner analogous to cascade reinforcement, we suggest that introgression associated with hybridization not only influences between-species isolation but can also contribute to isolation within a species.
Sixty years of research on technology and human resource management: Looking back and looking forward
Authors: Kim Sunghoon , Wang Ying , Boon Corine 
Published: November 2020

AbstractTechnology has changed the way we work and how companies manage their employees. This article reviews 60 years of research on the relationship between technology and human resource management, as represented in Human Resource Management. Based on 154 articles, we identify recurring and evolving patterns of research on technology across three time periods (separated by the advent of the personal computer in 1977 and by the popularization of consumer internet services in 1997), three perspectives on technology (tool, proxy, and ensemble view of technology), and three thematic streams (the impact of technology on jobs and organizations, the utilization of technology in HR activities, and the management of technology workers). Drawing on patterns of research that emerged in the past, we provide suggestions for future HR research on newly arriving technology.
Is the risk of childhood leukaemia associated with socioeconomic measures in Denmark? A nationwide register‐based case‐control study
Authors: Erdmann Friederike , Hvidtfeldt Ulla Arthur , Feychting Maria , Sørensen Mette , Raaschou‐Nielsen Ole 
Published: November 2020

AbstractThe aetiology of childhood leukaemia is poorly understood. Knowledge about differences in risk by socioeconomic status (SES) may enhance etiologic insights. We conducted a nationwide register‐based case‐control study to evaluate socioeconomic differences in the risk of childhood leukaemia in Denmark and to access whether associations varied by different measures of SES, time point of assessment, leukaemia type and age at diagnosis. We identified all cases of leukaemia in children aged 0 to 19 years, born and diagnosed between 1980 and 2013 from the Danish Cancer Registry (N = 1336) and sampled four individually matched controls per case (N = 5330). We used conditional logistic regression models for analysis. Medium and high level of parental education was associated with a higher risk of acute myeloid leukaemia (AML) in the offspring, mainly driven by children diagnosed at ages 0 to 4 years [odds ratio (OR) for high maternal education = 3.07; 95% confidence interval (CI): 1.44‐6.55]. We also observed a modestly increased risk for lymphoid leukaemia (LL) in association with higher level of parental education, but only in children diagnosed at ages 5 to 19 years. Higher parental income was associated with an increased risk of LL but not AML among children aged 5 to 19 years at diagnosis (OR for high maternal income = 2.78; 95% CI: 1.32‐5.89). Results for neighbourhood SES measures indicated null associations. Bias or under‐ascertainment of cases among families with low income or basic education are unlikely to explain the observed socioeconomic differences. Future research addressing explicitly the underlying mechanisms of our results may help to enhance etiologic insights of the disease.
Ring opening of 2,6‐diaryl‐3,5‐diphenyl piperidine‐4‐one by acetic acid: Structural studies and Hirshfeld surface analysis of (E)‐4‐aryl‐1,3‐diphenylbut‐3‐en‐2‐ones
Authors: Vengatesh Gopal , Sundaravadivelu Manthiram , Muthusubramanian Shanmugam 
Published: November 2020

AbstractSix α,β‐unsaturated carbonyl compounds have been obtained from 2,6‐diaryl‐3,5‐diphenylpiperidine‐4‐one by the treatment with acetic acid. A plausible mechanism for the ring opening of 2,6‐diaryl‐3,5‐diphenyl piperidin‐4‐ones is proposed. The resultant (E)‐4‐aryl‐1,3‐diphenylbut‐3‐en‐2‐ones have been characterized by 1H and 13C nuclear magnetic resonance (NMR) spectral studies. One of the compounds was completely characterized by 2D NMR techniques, and structure of the compound is further proved by single‐crystal X‐ray diffraction (XRD) analysis. The crystal structure, three‐dimensional framework of crystal, and Hirshfeld surface analysis of two of the compounds have been discussed. In the crystals, molecules are mainly linked by CH···O hydrogen bonding interactions, and this interaction forms an inversion dimer with R21(6) and R21(10) ring motifs in one of the compounds. Hirshfeld surface indicates the dominance of H···H contacts on the overall surface.
Opioid Usage and Prescribing Predictors Following Transoral Robotic Surgery for Oropharyngeal Cancer
Authors: Abt Nicholas B. , Holcomb Andrew J. , Feng Allen L. , Suresh Krish , Mokhtari Tara E. , McHugh Christopher I. , Parikh Anuraag S. , Faden Daniel L. , Deschler Daniel G. , Varvares Mark A. , Lin Derrick T. , Richmon Jeremy D. 
Published: November 2020

Objective/HypothesisPain management following transoral robotic surgery (TORS) varies widely. We aim to quantify opioid usage following TORS for oropharyngeal squamous cell carcinoma (OPSCC) and identify prescribing predictors.Study DesignRetrospective cohort study.MethodsA consecutive series of 138 patients undergoing TORS for OPSCC were reviewed from 2016 to 2019. Opioid usage (standardized to morphine milligram equivalents [MME]) was gathered for 12 months post‐surgery via prescribing record cross‐check with the Massachusetts Prescription Awareness Tool.ResultsOf 138 OPSCC TORS patients, 92.8% were human papillomavirus (HPV) positive. Adjuvant therapy included radiation (XRT;67.4%) and chemoradiation (cXRT;6.5%). Total MME usage from start of treatment averaged 1395.7 MMEs with 76.4% receiving three prescriptions or less. Categorical analysis showed age <65, male sex, overweight BMI, lower frailty, former smokers, HPV+, higher T stage, and BOT subsite to be associated with increased MMEs. Adjuvant therapy significantly increased MMEs (TORS+XRT:1646.2; TORS+cXRT:2385.0; TORS alone:554.7 [P < .001]) and 12‐month opioid prescription totals (TORS+XRT:3.2; TORS+cXRT:5.5; TORS alone:1.6 [P < .001]). Adjuvant therapy increased time to taper (total MME in TORS alone versus TORS+XRT/cXRT: 0 to 3 months:428.2 versus 845.5, 4 to 6 months:46.8 versus 541.8, 7 to 9 months:12.4 versus 178.6, 10 to 12 months:11.0 versus 4.4,[P < .001]). Positive predictors of opioid prescribing at the 4‐ to 6‐month and 4‐ to 12‐month intervals included adjuvant therapy (odds ratio [OR]:5.56 and 4.51) and mFI‐5 score ≥3 (OR:36.67 and 31.94). Following TORS at 6‐, 9‐, and 12‐month, 15.7%, 6.6%, and 4.1% were still using opioids.ConclusionsIn OPSCC treated with TORS, opioid use tapers faster for surgery alone versus with adjuvant therapy. Opioid prescribing risks include adjuvant therapy and higher frailty index.Level of Evidence4 Laryngoscope, 131:E1888–E1894, 2021
Nonconjugated Biocompatible Macromolecular Luminogens for Sensing and Removals of Fe(III) and Cu(II): DFT Studies on Selective Coordination(s) and On‐Off Sensing
Authors: Dutta Arnab , Mahapatra Manas , Deb Mousumi , Ghosh Narendra Nath , Chattopadhyay Pijush Kanti , Singha Nayan Ranjan 
Published: November 2020

AbstractThis work reports the design and synthesis of two nonaromatic biocompatible macromolecular luminogens, i.e., 2‐(dimethylamino)ethyl methacrylate‐co‐2‐(dimethylamino)ethyl 3‐(N‐(methylol)acrylamido)‐2‐methylpropanoate‐co‐N‐(methylol)acrylamide/DMAEMA‐co‐DMAENMAMP‐co‐NMA (P1) and methacrylic acid‐co‐3‐(N‐(methylol)acrylamido)‐2‐methylpropanoic acid‐co‐N‐(methylol)acrylamide/MEA‐co‐NMAMPA‐co‐NMA (P2), prepared through in situ anchored acrylamido‐ester/DMAENMAMP and acrylamido‐acid/NMAMPA third comonomers, respectively, in a facile polymerization of two non‐luminous monomers in water medium to circumvent the drawbacks related to aggregation‐caused quenching of aromatic luminogens. The structures of P1/P2, in situ anchored comonomers, fluorophores, N‐branching associated n–π* interactions, and hydrogen bonding assisted aggregation‐enhanced emissions are comprehended by nuclear magnetic resonance, Fourier transform infrared (FTIR), X‐ray photoelectron spectroscopy (XPS), ultraviolet‐visible, thermogravimetric analysis (TGA), dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence lifetime, and fluorescence imaging. P1 and P2 are appropriate for sensitive detections/exclusions of Fe(III)/Cu(II) and cell‐imaging. The intrinsic fluorescence, on‐off sensing, selective coordinations of Fe(III) and Cu(II) with fluorophores, emission quenching mechanisms, and removals of Fe(III) and Cu(II) are investigated by DFT/NTO analyses of P1/P2 and Fe(III)‐P1 and Cu(II)‐P2 complexes, XPS, and isotherms and kinetics parameters. The excellent biocompatibilities, comparable limit of detections, i.e., 1.70 × 10−7 and 1.59 × 10−7 [m], and higher adsorption capacities, i.e., 77.25 and 154.13 mg g−1, at low ppm; 303 K; and pH = 7 compel P1/P2 to be acceptable for multipurpose applications.