bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dinuclear ZnII Complexes Exhibiting Thermally Activated Delayed Fluorescence and Luminescence Polymorphism
Authors: Xiong Jinfan , Li Kai , Teng Teng , Chang Xiaoyong , Wei Yaxiong , Wu Chao , Yang Chuluo 
Published: March 2020

AbstractZnII complexes exhibiting strong emission in the solid state remain scarce, and most of them exhibit only prompt fluorescence. Herein the synthesis, structures, and photoluminescence properties of two ZnII complexes containing new donor–acceptor ligands is reported. The new ZnII complexes have dinuclear structures in which each metal ion adopts a distorted square‐pyramidal geometry. The ZnII complexes show strong emission in the solid state with quantum yields up to 50 %. Variable‐temperature transient photoluminescence studies revealed an emission mechanism involving prompt and thermally activated delayed fluorescence (TADF). DFT calculations showed well‐separated HOMO and LUMO in the ground state and small excited singlet–triplet energy splitting, accounting for the TADF. The complexes also exhibit different emission colors in the as‐synthesized powder state and in single crystals, that is, they exhibit luminescence polymorphism. The single‐crystal emission is responsive to mechanical grinding and was characterized by powder XRD.
Novel, Dual Target‐Directed Annelated Xanthine Derivatives Acting on Adenosine Receptors and Monoamine Oxidase B
Authors: Kuder Kamil J. , Załuski Michał , Schabikowski Jakub , Latacz Gniewomir , Olejarz‐Maciej Agnieszka , Jaśko Piotr , Doroz‐Płonka Agata , Brockmann Andreas , Müller Christa E. , Kieć‐Kononowicz Katarzyna 
Published: March 2020

AbstractAnnelated purinedione derivatives have been shown to act as possible multiple‐target ligands, addressing adenosine receptors and monoaminooxidases. In this study, based on our previous results, novel annelated pyrimido‐ and diazepino[2,1‐f]purinedione derivatives were designed as dual‐target‐directed ligands combining A2A adenosine receptor (AR) antagonistic activity with blocking monoamine oxidase B. A library of 19 novel compounds was synthesized and biologically evaluated in radioligand binding studies at AR subtypes and for their ability to inhibit MAO‐B. This allowed 9‐(2‐chloro‐6‐fluorobenzyl)‐3‐ethyl‐1‐methyl‐6,7,8,9‐tetrahydropyrimido[2,1‐f]purine‐2,4(1H,3H)‐dione (13 e; Ki human A2AAR: 264 nM and IC50 human MAO‐B: 243 nM) to be identified as the most potent dual‐acting ligand from this series. ADMET parameters were estimated in vitro, and analysis of the structure‐activity relationships was complemented by molecular‐docking studies based on previously published X‐ray structures of the protein targets. Such dual‐acting ligands, by selectively blocking A2A AR, accompanied by the inhibition of dopamine metabolizing enzyme MAO‐B, might provide symptomatic and neuroprotective effects in, among others, the treatment of Parkinson disease
Aryloxy Triester Phosphoramidates as Phosphoserine Prodrugs: A Proof of Concept Study
Authors: Miccoli Ageo , Dhiani Binar A. , Thornton Peter J. , Lambourne Olivia A. , James Edward , Kadri Hachemi , Mehellou Youcef 
Published: March 2020

AbstractThe specific targeting of protein‐protein interactions by phosphoserine‐containing small molecules has been scarce due to the dephosphorylation of phosphoserine and its charged nature at physiological pH, which hinder its uptake into cells. To address these issues, we herein report the synthesis of phosphoserine aryloxy triester phosphoramidates as phosphoserine prodrugs that are enzymatically metabolized to release phosphoserine. This phosphoserine‐masking approach was applied to a phosphoserine‐containing inhibitor of 14‐3‐3 dimerization, and the generated prodrugs exhibited improved pharmacological activity. Collectively, this provided a proof of concept that the masking of phosphoserine with biocleavable aryloxy triester phosphoramidate masking groups is a viable intracellular delivery system for phosphoserine‐containing molecules. Ultimately, this will facilitate the discovery of phosphoserine‐containing small‐molecule therapeutics.
Enhanced Efficacy of Gefitinib in Drug‐Sensitive and Drug‐Resistant Cancer Cell Lines after Arming with a Singlet Oxygen Releasing Moiety
Authors: Huang Kunshan , Huo Beibei , Li Dongyao , Xue Jinping , Chen Juanjuan 
Published: March 2020

AbstractAttractive results have been achieved with small‐molecule target‐based drugs in the anticancer field; however, enhancing their treatment effect and solving the problem of drug resistance remain key concerns worldwide. Inspired by the specific affinity of gefitinib for tumour cells and the strong oxidation capacity of singlet oxygen, we combined a chemically generated singlet oxygen moiety with the small‐molecule targeted drug gefitinib to improve its anticancer effect. We designed and synthesised a novel compound (Y5‐1), in which a small‐molecule targeted therapy agent (gefitinib) and a singlet oxygen (provided by an in vitro photodynamic reaction) thermally controlled releasing moiety are covalently conjugated. We demonstrated that the introduction of the singlet oxygen thermally controlled releasing moiety enhanced the anticancer activities of gefitinib. The results of this study are expected to provide a novel strategy to enhance the effect of chemotherapy drugs on drug‐resistant cell lines.
Synthesis and Biological Evaluation of Hapten‐Clicked Analogues of The Antigenic Peptide Melan‐A/MART‐126(27L)‐35
Authors: Tarbe Marion , Miles John J. , Edwards Emily S. J. , Miles Kim M. , Sewell Andrew K. , Baker Brian M. , Quideau Stéphane 
Published: March 2020

AbstractA click‐chemistry‐based approach was implemented to prepare peptidomimetics designed in silico and made from aromatic azides and a propargylated GIGI‐mimicking platform derived from the altered Melan‐A/MART‐126(27L)‐35 antigenic peptide ELAGIGILTV. The CuI‐catalyzed Huisgen cycloaddition was carried out on solid support to generate rapidly a first series of peptidomimetics, which were evaluated for their capacity to dock at the interface between the major histocompatibility complex class‐I (MHC‐I) human leucocyte antigen (HLA)‐A2 and T‐cell receptors (TCRs). Despite being a weak HLA‐A2 ligand, one of these 11 first synthetic compounds bearing a p‐nitrobenzyl‐triazole side chain was recognized by the receptor proteins of Melan‐A/MART‐1‐specific T‐cells. After modification of the N and C termini of this agonist, which was intended to enhance HLA‐A2 binding, one of the resulting seven additional compounds triggered significant T‐cell responses. Thus, these results highlight the capacity of naturally circulating human TCRs that are specific for the native Melan‐A/MART‐126‐35 peptide to cross‐react with peptidomimetics bearing organic motifs structurally different from the native central amino acids.
Resolving Binding Events on the Multifunctional Human Serum Albumin
Authors: Wenskowsky Lea , Wagner Michael , Reusch Johannes , Schreuder Herman , Matter Hans , Opatz Till , Petry Stefan Matthias 
Published: March 2020

AbstractPhysiological processes rely on initial recognition events between cellular components and other molecules or modalities. Biomolecules can have multiple sites or mode of interaction with other molecular entities, so that a resolution of the individual binding events in terms of spatial localization as well as association and dissociation kinetics is required for a meaningful description. Here we describe a trichromatic fluorescent binding‐ and displacement assay for simultaneous monitoring of three individual binding sites in the important transporter and binding protein human serum albumin. Independent investigations of binding events by X‐ray crystallography and time‐resolved dynamics measurements (switchSENSE technology) confirm the validity of the assay, the localization of binding sites and furthermore reveal conformational changes associated with ligand binding. The described assay system allows for the detailed characterization of albumin‐binding drugs and is therefore well‐suited for prediction of drug‐drug and drug‐food interactions. Moreover, conformational changes, usually associated with binding events, can also be analyzed.
Effects of the appearance care program for breast cancer patients receiving chemotherapy: A mixed method study
Authors: Ikeda Mari , Tamai Nao , Kanai Hisako , Osaka Misato , Kondo Kazuko , Yamazaki Takako , Sanada Hiromi , Kamibeppu Kiyoko 
Published: March 2020

AbstractBackgroundTreatment of breast cancer entails surgery, often followed by chemotherapy. Alopecia is a major, intractable side effect with potentially profound impacts on appearance. We developed a nurse‐facilitated program targeting appearance‐related symptoms.AimsThis study explored the effects of the appearance care program on quality of life (QOL). The program was delivered across three sessions, each involving personal reflections on appearance concerns, short lectures on skincare and makeover techniques, and small group discussions.Method and ResultsSeventy‐two women who attended the appearance care program were invited to participate. We employed a mixed‐method design combining quantitative and qualitative methods. QOL instruments were used to measure effects of the program at the first and final sessions and at a one‐month follow‐up. The qualitative data were collected as open‐ended notes regarding participants' perception of the program at the final session and at a one‐month follow‐up. Fifty‐seven women completed all three sessions. Of them, 55 participated in this study. Their mean age was 46.4 years; 39 (70.9%) had partners, and 34 (61.8%) had children. Most participants experienced hair loss at one‐month post‐program; however, cancer‐specific QOL improved after attending the program. Patients' experience of fatigue and weakness may explain observations of decreased physical well‐being. Emotional well‐being continued to increase 1 month following the program, while social and functional well‐being was consistent. Participants felt empowered by the information on skincare and cosmetic techniques and valued the intimate support from the group members facing similar circumstances.ConclusionsThis study showed that the appearance care program increased or maintained the well‐being of participants. Findings suggest the appearance care program which promoted group sharing experiences empowered participants and may have enhanced their coping strategies.
A noteworthy treatment of metastatic small‐cell lung cancer with afatinib, followed by subsequent development of rare metastatic lesions in the ascending and sigmoid colon
Authors: Hsiao Shih‐Chuan , Chen Yi‐Hsien , Lo Ching‐Chu , Lin Ching‐I 
Published: March 2020

AbstractBackgroundSmall‐cell lung cancer (SCLC) represents a group of highly fatal diseases with a tendency toward fast growth, early metastasis, and easy development of chemotherapy resistance. In the past 30 years, few advances have been made in the systemic treatment of SCLC, and cisplatin/etoposide has remained the standard of care for limited‐stage SCLC and, in combination with radiotherapy, extensive‐stage SCLC. The preferred metastatic sites of SCLC include the brain, liver, adrenal glands, bone, and bone marrow. However, bowel metastasis caused by SCLC is extremely rarely proved in patients while they are still alive (although autopsy studies suggest that silent metastases to the bowel are more common), and the standard treatment for bowel metastasis has never been reported. The mean time between the identification of gastrointestinal metastasis and mortality in patients with lung cancer is 100.6 days, with a range of 21–145 days.CaseWe report the case of a patient with extensive SCLC (including brain metastasis), in which exon 19 deletion of epidermal growth factor receptor (EGFR) was detected. She initially refused chemotherapy and cranial radiotherapy and instead only agreed to oral target therapy. The second‐generation EGFR‐tyrosine kinase inhibitor (TKI), afatinib, was administered to the patient, and partial remission, including smaller metastatic brain tumors, was noted. Even though the subsequent development of rare metastatic lesions in the ascending and sigmoid colon was proved by colonoscopic biopsies, the prolonged overall survival (400 days) without standard treatment was marked in this case.ConclusionThe patient with extensive metastasis of SCLC did not receive standard systemic chemotherapy. Instead, she initially received second‐generation EGFR‐TKI afatinib alone and later on whole brain radiotherapy as well (3 weeks before she expired). The prolonged overall survival of 400 days was marked and is worthy of sharing and further investigation.
Multihop routing protocols on wireless ad hoc sensor networks with modified MAC layer and broadcasting scheme
Authors: Nguyen Tung T. 
Published: March 2020

SummaryMost sensor devices are equipped with local batteries, placing a limitation on available energy, assuming that replacement of batteries is not feasible. This constraint limits the operation time of sensor networks. In many scenarios, sensors are operating in remote or dangerous areas, and it is impractical to replace or recharge the battery of the sensors. In some scenarios, such as machine monitoring or medical monitoring, it is more convenient to install new sensors than to replace the battery of the sensor nodes. The focus of this article is to design routing methods to achieve the maximum operation time of sensor networks (the number of rounds to transmit data) under the constraint of battery sources. Therefore, the main contribution of this research is not to change any characteristic of the network infrastructure, but to define the interactions between nodes to achieve better energy efficiency.
Reverse introduction of two‐ and six‐rowed barley lines from the United States into Egypt
Authors: Elbasyoni Ibrahim S. , Morsy Sabah M. , Naser Mahmoud , Ali Heba , Smith Kevin P. , Baenziger P. Stephen 
Published: March 2020

AbstractIn the current study, 248 two‐rowed and another 253 six‐rowed spring barley (Hordeum vulgare L.) breeding lines from several US barley breeding programs were evaluated in multiple locations in Egypt to select for potentially adapted lines. The introduced plant materials were planted in two locations during three growing seasons (2015, 2016, and 2017). The focus of the first growing season was to increase available seeds and collect preliminary observations. During the second and third growing seasons, the advanced plant materials and local check cultivars were planted in an incomplete block design in two replicates within three locations. Grain yield, leaf rust, number of days to flowering, and plant height were measured. Based on grain yield production, the top 94 lines from the two‐rowed and 100 from the six‐rowed barley lines were selected and advanced for further evaluation in 2017. The introduced materials contained several lines that consistently outperformed the check cultivars. Therefore, these lines could be used as parents to improve barley production and enhance genetic diversity or be directly released as cultivars after appropriate testing in Egypt.
Four‐port shared rectangular radiator with defected ground for wireless application
Authors: Chouhan Sanjay , Malviya Leeladhar 
Published: March 2020

SummaryIn this research work, a modified shared rectangular radiator is proposed for 5.7‐GHz wireless application using multiple cuts and partially stepped ground. The shared design requires no isolating structure to decouple the ports. The proposed shared geometry produces >13 dB isolation in the 4.4‐ to 6.4‐GHz operating band. The gain varies from 3.0 to 6.2 dBi, and radiation efficiency is >70 % in the band. The mutual coupling among the port is reduced by orthogonal arrangement of ports, and envelope correlation coefficient (ECC) is <0.04 in the presented band. Apart from this, isolation in the proposed shared radiator is enhanced by additional multiple cuts with stepped ground. The indoor‐outdoor suitability of multiple input multiple output (MIMO) antenna for isotropic and Gaussian medium is checked by mean effective gain (MEG) and specific absorption rate (SAR). The presented results of MEG and SAR fulfill the required safety norms as per the ITU for different environments.
Preparation, characterization, and sonodynamic antitumor effect of the folate receptor targeted FA‐EN‐β‐CD containing hematoporphyrin in vitro
Authors: Wang Chuanjin , Du Fuqiang 
Published: March 2020

AbstractTo improve water solubility, reduce phototoxicity and increase the tumor‐targeting ability of hematoporphyrin (Hp) as a sonosensitizer for sonodynamic therapy under ultrasonic conditions, a novel folate receptor (FR)‐targeted, folate‐conjugated ethylenediamine‐β‐cyclodextrin (FA‐EN‐β‐CD) containing Hp (FA‐EN‐β‐CD‐Hp) was constructed. β‐Cyclodextrin containing Hp (β‐CD‐Hp) was also established as a nontargeted control. The inclusion efficiencies of Hp in FA‐EN‐β‐CD‐Hp and β‐CD‐Hp were determined to be 90.4 ± 2.7% (wt/wt) and 92.5 ± 3.4% (wt/wt), respectively. Growth inhibition rates in HepG‐2 cells in vitro were assessed upon ultrasound exposure. The results indicated that the growth inhibition rates of FA‐EN‐β‐CD‐Hp, β‐CD‐Hp, and F‐Hp (Hp: 150 μg/ml) reached 96.4 ± 3.6%, 53.4 ± 3.4%, and 48.2 ± 2.8%, respectively. These results indicated that FA‐EN‐β‐CD‐Hp is a promising drug delivery system in the field of sonodynamic cancer therapy.
Evolution of major histocompatibility complex class I genes in the sable Martes zibellina (Carnivora, Mustelidae)
Authors: Zhao Baojun , Zhang Xue , Li Bo , Du Pengfei , Shi Lupeng , Dong Yuehuan , Gao Xiaodong , Sha Weilai , Zhang Honghai 
Published: March 2020

AbstractThe molecules encoded by major histocompatibility complex (MHC) genes play an essential role in the adaptive immune response among vertebrates. We investigated the molecular evolution of MHC class I genes in the sable Martes zibellina. We isolated 26 MHC class I sequences, including 12 putatively functional sequences and 14 pseudogene sequences, from 24 individuals from two geographic areas of northeast China. The number of putatively functional sequences found in a single individual ranged from one to five, which might be at least 1–3 loci. We found that both balancing selection and recombination contribute to evolution of MHC class I genes in M. zibellina. In addition, we identified a candidate nonclassical MHC class I lineage in Carnivora, which may have preceded the divergence (about 52–57 Mya) of Caniformia and Feliformia. This may contribute to further understanding of the origin and evolution of nonclassical MHC class I genes. Our study provides important immune information of MHC for M. zibellina, as well as other carnivores.
Insulin/carbohydrates ratio during the first 6‐month therapy with insulin degludec in a paediatric population with type 1 diabetes previously treated with insulin glargine. An observational longitudinal study
Authors: Tumini Stefano , Iacono Olimpia , Comegna Laura , Fioretti Elisabetta , Guidone Paola , Levantini Gabriella , Panichi Daniele , Catenaro Milena , Rossi Ilaria , Amaro Flavia , Graziano Giusi , Rossi Maria Chiara , Cipriano Paola 
Published: March 2020

AbstractBackgroundNo data exist about the changes induced by the transition from first‐generation long‐acting insulins to second‐generation long‐acting analogues in the paediatric population.ObjectiveTo assess changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100.SubjectsAll patients treated with degludec under routine clinical practice conditions were retrospectively analysed.MethodsNonprofit observational retrospective study. Changes during the follow‐up in mean CHO/I ratio were assessed using longitudinal linear models for repeated measures. Rate of hypoglycaemia, ketoacidosis and adverse events was evaluated.ResultsOverall, 51 children (mean age 13.8 ± 4.6 years; mean diabetes duration 5.8 ± 3.9 years) started therapy with degludec in the period between April 2017 and April 2018. I:CHO ratio before starting degludec therapy significantly differed among the three meals, being the lowest at breakfast and the highest at dinner. After introducing degludec, I:CHO ratio at lunch (−1.29 95% CI −2.02;−0.57) and at dinner (−3.08 95% CI −4.35;−1.8) significantly decreased, while it slightly increased at breakfast (+1.37 95% CI 0.47;2.28). No episodes of severe hypoglycaemia, ketoacidosis and adverse event were recorded during 6 months.ConclusionsOur data show that the use of degludec is associated with a significant change in the I:CHO ratio at the different meals compared to the previous glargine therapy. This could derive from the flat and prolonged pharmacokinetic profile of degludec. This has important clinical implications for daily insulin dose adjustments.
Non‐invasive telemedical care in heart failure patients and stroke: post hoc analysis of TIM‐HF and TIM‐HF2 trials
Authors: Tütüncü Serdar , Honold Marcus , Koehler Kerstin , Deckwart Oliver , Koehler Friedrich , Haeusler Karl Georg 
Published: March 2020

AbstractAimsPatients with chronic heart failure (CHF) have an increased risk of ischaemic stroke. We aimed to identify the incidence rate and factors associated with ischaemic stroke or transient ischaemic attack (TIA) in CHF patients as well as the impact of non‐invasive telemedical care (NITC) on acute stroke/TIA.Methods and resultsWe retrospectively analysed baseline characteristics of 2248 CHF patients enrolled to the prospective multicentre Telemedical Interventional Monitoring in Heart Failure study (TIM‐HF) and Telemedical Interventional Management in Heart Failure II study (TIM‐HF2), randomizing New York Heart Association (NYHA) II/III patients 1:1 to NITC or standard of care. Hospitalizations due to acute ischaemic stroke or TIA during a follow‐up of 12 months were analysed. Old age, hyperlipidaemia, lower body mass index, and peripheral arterial occlusive disease (PAOD) were independently associated with present cerebrovascular disease on enrolment. The stroke/TIA rate was 1.5 per 100 patients‐years within 12 months after randomization (n = 32, 1.4%). Rate of stroke/TIA within 12 months was in the intervention group similar compared with the control group (50.0% vs. 49.8%; P = 0.98) despite that the rate of newly detected atrial fibrillation (AF) was higher in the intervention group (14.1% vs. 1.6%; P < 0.001). A history of PAOD (OR 2.7, 95% CI 1.2–6.2; P = 0.02) and the highest tertile (OR 3.0, 95% CI 1.1–8.3) of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) on enrolment were associated with stroke/TIA during follow‐up. In patients who suffered acute stroke or TIA during follow‐up, echocardiography was part of the diagnostic workup in only 56% after hospital admission.ConclusionsAnnual rate of ischaemic stroke/TIA in NYHA II/III patients is low but higher in those with elevated NT‐proBNP levels and history of PAOD at baseline. NITC showed no impact on the stroke rate during 1 year follow‐up despite a significantly higher rate of newly detected AF. Irrespective of known CHF, echocardiography was often missing during in‐hospital diagnostic workup after acute stroke/TIA.