bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vinyl Groups Containing Tetraphenylethylene Derivatives as Fluorescent Probes Specific for Palladium and the Quenching Mechanism†
Authors: Liu Xiaoqing , Shang Yuxuan , Chen Zhong‐Ren 
Published: February 2021

Main observation and conclusionWe previously reported that a series of tetraphenylethylene (TPE)‐containing all‐hydrocarbon conjugated polymers exhibited a specific fluorescence quenching by palladium ions (Pd2+). To understand the quenching mechanism, herein we investigate the quenching behaviors of three TPE derivatives in the presence of Pd2+. Each TPE derivative, consisting of TPE unit and terminal vinyl groups, shows an aggregation‐induced emission (AIE) and its fluorescence turns off specifically to Pd2+. The sensitivity is enhanced with increasing numbers of vinyl groups in the molecules. By time‐resolved fluorescence measurement, a dynamic quenching is observed where the fluorescence lifetime is reduced with Pd2+. Specifically, the quenching occurs via the electron transfer in the excited states, as suggested by the disappearance of the stimulated emission band in transient absorption spectra. A theoretical calculation on the excited states identifies intermolecular electron transfer from TPE derivatives to Pd, especially for electron–rich TPE derivative. The mechanism can be general for the design of novel AIE active chemosensors.
Triple‐marker immunohistochemical assessment of muscle‐invasive bladder cancer: Is there prognostic significance?
Authors: Labban Muhieddine , Najdi Jad , Mukherji Deborah , Abou‐Kheir Wassim , Tabbarah Abeer , El‐Hajj Albert 
Published: February 2021

AbstractBackgroundBladder cancer is the ninth most common cancer worldwide, and the third most common cancer in Lebanon. Immunohistochemistry (IHC) has been used to stratify muscle‐invasive bladder cancer (MIBC) into different subtypes. However, to our knowledge, there exists no study that investigates the use of this low‐cost technique to predict prognosis in bladder cancer patients in our region.AimTo examine the feasibility of low‐cost triple‐marker IHC assessment for MIBC subtyping in order to predict patients' survival and cisplatin sensitivity.Methods and resultsWe collected the specimens of deceased patients diagnosed with MIBC on pathology at our institution. For each case, tumor tissue blocks were retrieved and stained for hematoxylin and eosin in addition to three molecular markers by IHC: cytokeratin 5/6, cytokeratin 14 staining basal BC, and GATA3 staining luminal BC. A cut‐off of ≥20% was set as positive. Kaplan‐Meier curves were built, factored by BC subtype, to predict overall survival (OS), disease‐specific survival (DSS), and progression‐free survival (PFS). Hazard ratios in Cox regression were also created accounting for oncological factors and BC subtype.We categorized specimens as either luminal (GATA3 positive only) (n = 21; 56.7%) or as double‐positive (GATA3 and basal cytokeratin 5/6 or cytokeratin 14 positive) (n = 16; 43.3%). The overall median survival was similar between the two categories (27.0 ± 4.82 months). Numbers favored luminal disease for PFS (Breslow P = .032). After adjusting for covariates, luminal molecular expression predicted PFS (0.28; [0.09‐0.94]). Yet, the Cox model was not able to identify any predictors of OS or DSS.ConclusionSpecimens enriched with only a luminal molecular profile were more likely to exhibit cisplatin sensitivity. Despite the absence of guidelines recommending the utilization of molecular profiling in clinic practice, triple‐marker IHC could serve as a potential low‐cost prognostic indicator to identify patients at high risk of progression.
Trajectories of depression in psychotherapy: How client characteristics predict clinical improvement
Authors: Lin Tao , Farber Barry A. 
Published: February 2021

AbstractObjectiveThe current study aims to ascertain the trajectories of psychotherapy clients’ symptom change and identify client factors that predict treatment outcome.MethodWe conducted a latent growth mixture model (LGMM) to identify the change trajectories of 44 clients’ depression scores during psychotherapy. Client characteristics were then explored to determine whether any were associated with change trajectories. We examined whether the number of physician visits and/or client self‐concealment scores predict 63 clients’ improvement after controlling for initial symptom severity.ResultsTwo trajectories of clients’ symptom change were identified: nonimprovers (52.3%) and improvers (47.7%). Nonimprovers had higher levels of self‐concealment and baseline depression than improvers. The number of physician visits was associated with higher depression scores at baseline and greater clinical improvement during psychotherapy.ConclusionClients showed distinct trajectories of symptom change in psychotherapy. Early identification of clients at risk for treatment failure may increase the probability of therapeutic success.
DVHnet: A deep learning‐based prediction of patient‐specific dose volume histograms for radiotherapy planning
Authors: Chen Xinyuan , Men Kuo , Zhu Ji , Yang Bining , Li Minghui , Liu Zhiqiang , Yan Xuena , Yi Junlin , Dai Jianrong 
Published: February 2021

PurposeTo develop a deep learning method to predict patient‐specific dose volume histograms (DVHs) for radiotherapy planning.MethodsPatient data included 180 cases with nasopharyngeal cancer, of which 153 cases were used for training and 27 for testing. A network (named “DVHnet”) based on a convolutional neural network (CNN) was designed for directly predicting DVHs of organs at risk (OARs). Two‐channel images with contoured structures were generated as the inputs for training the model. A one‐dimensional array consisting of 256 continuous volume percentages on a DVH curve for each slice was calculated as the corresponding output. The combined DVH was then calculated. Sixteen OARs were modeled in the study. Prediction accuracy was evaluated against the corresponding DVH curve of ground truth (GT) plans. A global DVH analysis and critical dosimetry metrics for each OAR were calculated for quantitative evaluation. The performance of DVHnet also was evaluated against two baselines: DosemapNet (developed by our research group) and commercial RapidPlan software.ResultsThe predicted mean difference in average dose of all OARs using DVHnet was 0.30 ± 0.95 Gy. And the predicted differences in D2% and D50 can be control within 2.32 and 0.69 Gy. For most OARs, there were no obvious differences between the dosimetric metrics of the predicted and GT values for both DVHnet and DosemapNet (P ≥ 0.05). Only the predicted D2% of the optic organs for DVHnet, and of brain stem PRV for DosemapNet displayed statistically significant differences. Except for the optic organs, DVHnet performs better than or comparably with RapidPlan. The mean difference in proportion of points of interest was 3.59% ± 7.78%.ConclusionsA deep learning network model was developed to automatically extract useful features for accurate prediction of patient‐specific DVH curves directly. The performance of DVHnet was comparable to DosemapNet and RapidPlan.
Iron(III)‐tCDTA derivatives as MRI contrast agents: Increased T1 relaxivities at higher magnetic field strength and pH sensing
Authors: Xie Jing , Haeckel Akvile , Hauptmann Ralf , Ray Iweta Pryjomska , Limberg Christian , Kulak Nora , Hamm Bernd , Schellenberger Eyk 
Published: February 2021

PurposeLow molecular weight iron(III) complex‐based contrast agents (IBCA) including iron(III) trans‐cyclohexane diamine tetraacetic acid [Fe(tCDTA)]− could serve as alternatives to gadolinium‐based contrast agents in MRI. In search for IBCA with enhanced properties, we synthesized derivatives of [Fe(tCDTA)]− and compared their contrast effects.MethodsTrans‐cyclohexane diamine tetraacetic acid (tCDTA) was chemically modified in 2 steps: first the monoanhydride of Trans‐cyclohexane diamine tetraacetic acid was generated, and then it was coupled to amines in the second step. After purification, the chelators were analyzed by high‐performance liquid chromatography, mass spectrometry, and NMR spectrometry. The chelators were complexed with iron(III), and the relaxivities of the complexes were measured at 0.94, 1.5, 3, and 7 Tesla. Kinetic stabilities of the complexes were analyzed spectrophotometrically and the redox properties by cyclic voltammetry.ResultsUsing ethylenediamine (en) and trans‐1,4‐diaminocyclohexane, we generated monomers and dimers of tCDTA: en‐tCDTA, en‐tCDTA‐dimer, trans‐1,4‐diaminocyclohexane‐tCDTA, and trans‐1,4‐diaminocyclohexane‐tCDTA‐dimer. The iron(III) complexes of these derivatives had similarly high stabilities as [Fe(tCDTA)]−. The iron(III) complexes of the trans‐1,4‐diaminocyclohexane derivatives had higher T1 relaxivities than [Fe(tCDTA)]− that increased with increasing magnetic field strengths and were highest at 6.8 L·mmol−1·s−1 per molecule for the dimer. Remarkably, the relaxivity of [Fe(en‐tCDTA)]+ had a threefold increase from neutral pH toward pH6.ConclusionFour iron(III) complexes with similar stability in comparison to [Fe(tCDTA)]− were synthesized. The relaxivities of trans‐1,4‐diaminocyclohexane‐tCDTA and trans‐1,4‐diaminocyclohexane‐tCDTA‐dimer complexes were in the same range as gadolinium‐based contrast agents at 3 Tesla. The [Fe(en‐tCDTA)]+ complex is a pH sensor at weakly acidic pH levels, which are typical for various cancer types.
Pharmaceutical co‐crystal: An alternative strategy for enhanced physicochemical properties and drug synergy
Authors: Ngilirabanga Jean Baptiste , Samsodien Halima 
Published: February 2021

AbstractA growing number of co‐crystals in the literature are proof of how significant the co‐crystallization concept has become. Co‐crystallization enhances physicochemical properties through the formation of intermolecular interactions between a drug and a co‐former. A co‐crystal is a single crystalline material consisting of at least two molecular components solid at room temperature and present in a definite stoichiometric ratio. Pharmaceutical co‐crystals consist of the active pharmaceutical ingredient and the co‐former selected from generally regarded as safe (GRAS) list of the United State Food and Drug Administration. Co‐crystal formation requires an understanding of a drug target, a proper choice of a co‐former and is only achieved experimentally after several trials. Other beneficial co‐crystallization outcomes include binary eutectics, solid dispersions, amorphous forms, etc. Several key issues including design strategies, co‐former selection, and co‐crystallization methods; tradition and newly synthetic methods that are more efficient and suitable for large scale have been briefly described. The co‐crystal preference is demonstrated with a particular emphasis on multidrug co‐crystals and their contribution to the drug combination strategies used for the treatment and management of drug resistance and adverse side effects in serious medical conditions that require the administration of high doses such as HIV/AIDS, tuberculosis, and others.
Seaweed‐derived polymer‐based blue‐emitting C‐dots: synthesis, characterization and evaluation for iron sensing
Authors: Kholiya Faisal , Jauhari Smita , Meena Ramavatar 
Published: February 2021

AbstractIn recent times green and economical processes as well as sources have been in demand for the synthesis of carbon dots (C‐dots). This study demonstrates the smart utilization of seaweed‐derived polysaccharide as a green precursor for the synthesis of blue‐emitting fluorescent C‐dots using a simple, eco‐friendly and green method in an aqueous medium. The C‐dots prepared in this study were characterized using various techniques. The results confirmed that the prepared C‐dots have a cluster size of 100 nm with particle sizes in the range 5–10 nm. Prepared C‐dots emit blue photoluminescence with a good quantum yield ofca12%. Additionally, strong fluorescence quenching of C‐dots is observed in aqueous solution containing iron ions, and a selective decrease in fluorescence intensity makes it possible to determine iron in water samples in the range 0.025 to 30 ppm. Results of this work encourage us that abundantly available seaweed‐derived polysaccharides with no other commercial value could be used as green sources for the sustainable production of fluorescent, water‐soluble and biocompatible nanocarbon for selective iron sensing in aqueous solutions. © 2021 Society of Chemical Industry
Beyond history and “on a roll”: The list of the most well‐studied human protein structures and overall trends in the protein data bank
Authors: Li Zhen‐lu , Buck Matthias 
Published: February 2021

AbstractOf the roughly 20,000 canonical human protein sequences, as of January 20, 2021, 7,077 proteins have had their full or partial, medium‐ to high‐resolution structures determined by x‐ray crystallography or other methods. Which of these proteins dominate the protein data bank (the PDB) and why? In this paper, we list the 273 top human protein structures based on the number of their PDB entries. This set of proteins accounts for more than 40% of all available human PDB entries and represent past trends as well as current status for protein structural biology. We briefly discuss the relationship which some of the prominent protein structures have with protein research as a whole and mention their relevance to human diseases. The top‐10 soluble and membrane proteins are all well‐known (most of their first structures being deposited more than 30 years ago). Overall, there is no dramatic change in recent trends in the PDB. Remarkably, the number of structure depositions has grown nearly exponentially over the last 10 or more years (with a doubling time of 7 years for proteins, obtained from any organism). Growth in human protein structures is slightly faster (at 5.9 years). The information in this paper may be informative to senior scientists but also inspire researchers who are new to protein science, providing the year 2021 snap‐shot for the state of protein structural biology.
A detailed mapping of the readily accessible disulphide bonds in the cortex of wool fibres
Authors: Plowman Jeffrey E. , Miller Rachel E. , Thomas Ancy , Grosvenor Anita J. , Harland Duane P. , Deb‐Choudhury Santanu 
Published: February 2021

AbstractTrichocyte keratin intermediate filament proteins (keratins) and keratin associated proteins (KAPs) differ from their epithelial equivalents by having significantly more cysteine residues. Interactions between these cysteine residues within a mammalian fiber, and the putative regular organization of interactions are likely important for defining fiber mechanical properties, and thus biological functionality of hairs. Here we extend a previous study of cysteine accessibility under different levels of exposure to reducing compounds to detect a greater resolution of statistically non‐random interactions between individual residues from keratins and KAPs. We found that most of the cysteines with this non‐random accessibility in the KAPs were close to either the N‐ or C‐ terminal domains of these proteins. The most accessible non‐random cysteines in keratins were present in the head or tail domains, indicating the likely function of cysteine residues in these regions is in readily forming intermolecular bonds with KAPs. Some of the less accessible non‐random cysteines in keratins were discovered either close to or within the rod region in positions previously identified in human epithelial keratins as involved in crosslinking between the heterodimers of the tetramer. Our present study therefore provides a deeper understanding of the accessibility of disulfides in both keratins and KAPs and thus proves that there is some specificity to the disulfide bond interactions leading to these inter‐ and intra‐molecular bonds stabilizing the fiber structure. Furthermore, these suggest potential sites of interaction between keratins and KAPs as well as keratin‐keratin interactions in the trichocyte intermediate filament.
Protein dynamics analysis identifies candidate cancer driver genes and mutations inTCGAdata
Authors: Sayılgan Jan Fehmi , Haliloğlu Türkan , Gönen Mehmet 
Published: February 2021

AbstractRecently, it has been showed that cancer missense mutations selectively target the neighborhood of hinge residues, which are key sites in protein dynamics. Here, we show that this approach can be extended to find previously unknown candidate mutations and genes. To this aim, we developed a computational pipeline to detect significantly enriched three‐dimensional (3D) clustering of missense mutations around hinge residues. The hinge residues were detected by applying a Gaussian network model. By systematically analyzing the PanCancer compendium of somatic mutations in nearly 10 000 tumors from the Cancer Genome Atlas, we identified candidate genes and mutations in addition to well known ones. For instance, we found significantly enriched 3D clustering of missense mutations in known cancer genes including CDK4, CDKN2A, TCL1A, and MAPK1. Beside these known genes, we also identified significantly enriched 3D clustering of missense mutations around hinge residues in PLA2G4A, which may lead to excessive phosphorylation of the extracellular signal‐regulated kinases. Furthermore, we demonstrated that hinge‐based features improves pathogenicity prediction for missense mutations. Our results show that the consideration of clustering around hinge residues can help us explain the functional role of the mutations in known cancer genes and identify candidate genes.
Oxidation shuts down an auto‐inhibitory mechanism of von Willebrand factor
Authors: Tsai Rachel , Interlandi Gianluca 
Published: February 2021

AbstractThe blood protein von Willebrand factor (VWF) is a key link between inflammation and pathological thrombus formation. In particular, oxidation of methionine residues in specific domains of VWF due to the release of oxidants in inflammatory conditions has been linked to an increased platelet‐binding activity. However, the atomistic details of how methionine oxidation activates VWF have not been elucidated to date. Yet understanding the activation mechanism of VWF under oxidizing conditions can lead to the development of novel therapeutics that target VWF selectively under inflammatory conditions in order to reduce its thrombotic activity while maintaining its haemostatic function. In this manuscript, we used a combination of a dynamic flow assay and molecular dynamics (MD) simulations to investigate how methionine oxidation removes an auto‐inhibitory mechanism of VWF. Results from the dynamic flow assay revealed that oxidation does not directly activate the A1 domain, which is the domain in VWF that contains the binding site to the platelet surface receptor glycoprotein Ibα (GpIbα), but rather removes the inhibitory function of the neighboring A2 and A3 domains. Furthermore, the MD simulations combined with free energy perturbation calculations suggested that methionine oxidation may destabilize the binding interface between the A1 and A2 domains leading to unmasking of the GpIbα‐binding site in the A1 domain.
A survey of human histone H1 subtypes interaction networks: Implications for histones H1 functioning
Authors: Kowalski Andrzej 
Published: February 2021

AbstractTo show a spectrum of histone H1 subtypes (H1.1‐H1.5) activity realized through the protein‐protein interactions, data selected from APID resources were processed with sequence‐based bioinformatics approaches. Histone H1 subtypes participate in over half a thousand interactions with nuclear and cytosolic proteins (ComPPI database) engaged in the enzymatic activity and binding of nucleic acids and proteins (SIFTER tool). Small‐scale networks of H1 subtypes (STRING network) have similar topological parameters (P > .05) which are, however, different for networks hubs between subtype H1.1 and H1.4 and subtype H1.3 and H1.5 (P < .05) (Cytoscape software). Based on enriched GO terms (g:Profiler toolset) of interacting proteins, molecular function and biological process of networks hubs is related to RNA binding and ribosome biogenesis (subtype H1.1 and H1.4), cell cycle and cell division (subtype H1.3 and H1.5) and protein ubiquitination and degradation (subtype H1.2). The residue propensity (BIPSPI predictor) and secondary structures of interacting surfaces (GOR algorithm) as well as a value of equilibrium dissociation constant (ISLAND predictor) indicate that a type of H1 subtypes interactions is transient in term of the stability and medium‐strong in relation to the strength of binding. Histone H1 subtypes bind interacting partners in the intrinsic disorder‐dependent mode (FoldIndex, PrDOS predictor), according to the coupled folding and binding and mutual synergistic folding mechanism. These results evidence that multifunctional H1 subtypes operate via protein interactions in the networks of crucial cellular processes and, therefore, confirm a new histone H1 paradigm relating to its functioning in the protein‐protein interaction networks.
Policy for innovative entrepreneurship: Institutions, interventions, and societal challenges
Authors: Bradley Steven W. , Kim Phillip H. , Klein Peter G. , McMullen Jeffery S. , Wennberg Karl 
Published: February 2021

AbstractResearch SummaryInnovative entrepreneurship, defined as the creation of new products, services, production methods, or business models, is critical for firm, industry, and economic growth and a key determinant of societal well‐being. This special issue explores the roles of institutions and government policies in promoting or impeding innovative entrepreneurship. In this introductory editorial, we review theory and evidence on entrepreneurship at the macro‐institutional and micro‐policy levels, highlighting costs and benefits of alternative institutional environments and targeted policy interventions, as well as interactions within and across levels. We summarize the six papers in the special issue, discuss their contributions to the literature, and suggest how future work can build upon these and other papers to advance our understanding of the conditions and mechanisms underlying successful entrepreneurial innovation.Managerial SummaryInnovation and entrepreneurship bring new products and services to market, help firms and industries to grow, and generate improvements in social and economic life. The papers in this special issue explore the background conditions—laws, political processes, regulations, tax policy, subsidies, training programs, and more—that make entrepreneurship and innovation successful. Both “macro” and “micro” policies can stimulate successful entrepreneurial and innovative outcomes, but can also become politicized, be ineffective, and generate unintended consequences. The papers offer lessons to researchers, policymakers, and practitioners about making entrepreneurship and innovation more successful.