bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemiluminescence: From mechanism to applications in biological imaging and therapy
Authors: Wang Zhijia , Huang Jiaguo , Huang Jingsheng , Yu Bingran , Pu Kanyi , Xu Fu‐Jian 
Published: October 2021

AbstractChemiluminescence (CL) is an emission phenomenon induced by chemical reaction. Different from the photoluminescence, CL is free from external excitation source, which is expected to show great advantages such as higher signal‐to‐background ratio (SBR) in bioimaging, and deeper tissue penetration in photodynamic therapy (PDT). This review introduces the theoretical aspects of CL mechanism, such as classification, energy consideration and chemiexcited/photoexcited states. Application of CL in bioimaging is highlighted. In particular, the approaches to modulate the brightness and the wavelength of CL are summarized, which are two fundamental parameters in bioimaging. Finally, the application of CL in PDT is introduced. The potential challenges and perspectives of CL in bioimaging and therapy are also discussed.
Framework Nucleic Acids in Nuclear Medicine Imaging: Shedding Light on Nano–Bio Interactions
Authors: Wang Hao , Liu Qingyao , Lan Xiaoli , Jiang Dawei 
Published: October 2021

AbstractFramework nucleic acids (FNAs) represent nanoscale oligonucleotide assemblies with unique physical, chemical, and biological properties that are different from their building blocks. Following simple Watson–Crick base‐pairing rules, arbitrary DNA frameworks with diverse shapes, sizes, and dimensions can be prepared with high reproducibility and stability. The programmable assembly of nucleic acids into FNAs presents a highly controllable model for studies on nano–bio interactions and allows scrutiny of “nanostructure‐activity relationships.” Herein, we present an overview of recent progress with FNAs in the hope of deepening our understanding of nano–bio interfacing. We summarize the biological profiles and immune responses of various FNAs as functions of their shape, sizes, and surface charges. We then highlight recent efforts to apply FNAs for biomedical applications and discuss the challenges of FNAs for potential clinical translation. We believe that this Minireview can bring up‐to‐date information on FNAs and shed light on how their design may be harnessed for selective biomedical applications.
Case Study of N‐iPr versus N‐Mes Substituted NHC Ligands in Nickel Chemistry: The Coordination and Cyclotrimerization of Alkynes at [Ni(NHC)2]
Authors: Tendera Lukas , Helm Moritz , Krahfuss Mirjam J. , Kuntze‐Fechner Maximilian W. , Radius Udo 
Published: October 2021

AbstractA case study on the effect of the employment of two different NHC ligands in complexes [Ni(NHC)2] (NHC=iPr2ImMe 1Me, Mes2Im 2) and their behavior towards alkynes is reported. The reaction of a mixture of [Ni2(iPr2ImMe)4(μ‐(η2 : η2)‐COD)] B/ [Ni(iPr2ImMe)2(η4‐COD)] B’ or [Ni(Mes2Im)2] 2, respectively, with alkynes afforded complexes [Ni(NHC)2(η2‐alkyne)] (NHC=iPr2ImMe: alkyne=MeC≡CMe 3, H7C3C≡CC3H7 4, PhC≡CPh 5, MeOOCC≡CCOOMe 6, Me3SiC≡CSiMe3 7, PhC≡CMe 8, HC≡CC3H7 9, HC≡CPh 10, HC≡C(p‐Tol) 11, HC≡C(4‐tBu‐C6H4) 12, HC≡CCOOMe 13; NHC=Mes2Im: alkyne=MeC≡CMe 14, MeOOCC≡CCOOMe 15, PhC≡CMe 16, HC≡C(4‐tBu‐C6H4) 17, HC≡CCOOMe 18). Unusual rearrangement products 11 a and 12 a were identified for the complexes of the terminal alkynes HC≡C(p‐Tol) and HC≡C(4‐tBu‐C6H4), 11 and 12, which were formed by addition of a C−H bond of one of the NHC N‐iPr methyl groups to the C≡C triple bond of the coordinated alkyne. Complex 2 catalyzes the cyclotrimerization of 2‐butyne, 4‐octyne, diphenylacetylene, dimethyl acetylendicarboxylate, 1‐pentyne, phenylacetylene and methyl propiolate at ambient conditions, whereas 1Me is not a good catalyst. The reaction of 2 with 2‐butyne was monitored in some detail, which led to a mechanistic proposal for the cyclotrimerization at [Ni(NHC)2]. DFT calculations reveal that the differences between 1Me and 2 for alkyne cyclotrimerization lie in the energy profile of the initiation steps, which is very shallow for 2, and each step is associated with only a moderate energy change. The higher stability of 3 compared to 14 is attributed to a better electron transfer from the NHC to the metal to the alkyne ligand for the N‐alkyl substituted NHC, to enhanced Ni‐alkyne backbonding due to a smaller CNHC−Ni−CNHC bite angle, and to less steric repulsion of the smaller NHC iPr2ImMe.
Base‐Mediated Radical Borylation of Alkyl Sulfones
Authors: Huang Mingming , Hu Jiefeng , Krummenacher Ivo , Friedrich Alexandra , Braunschweig Holger , Westcott Stephen A. , Radius Udo , Marder Todd B. 
Published: October 2021

AbstractA practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal‐free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2neop2), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late‐stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates.
A case of splenic artery aneurysm and rupture in a patient on a vascular endothelial growth factor inhibitor for renal cell carcinoma
Authors: Tesolin Daniel , Alaref Amer , Ibrahim Mohammed F. K. 
Published: October 2021

AbstractBackgroundPazopanib is a vascular endothelial growth factor inhibitor that is used in the treatment of metastatic renal cell carcinoma. Post market reports demonstrate an increasing awareness of the association of arterial aneurysms and dissections with vascular endothelial growth factor inhibitor use, although, few reports exist for pazopanib.CaseHere we report a 69‐year‐old patient with minimal cardiovascular risk factors who developed a rupture of a splenic arterial aneurysm after more than 5 years of effective treatment with pazopanib for metastatic renal cell carcinoma.ConclusionThis case report outlines the necessity to monitor patients while on pazopanib, even when there are minimal risk factors and long periods of tolerance.
Pharmacokinetics and Safety of Letermovir and Midazolam Coadministration in Healthy Subjects
Authors: Kropeit Dirk , McCormick David , Erb‐Zohar Katharina , Stobernack Hans‐Peter , Zimmermann Holger , Rübsamen‐Schaeff Helga 
Published: October 2021

AbstractLetermovir is a human cytomegalovirus (CMV) terminase inhibitor for the prophylaxis of CMV infection and disease in allogeneic hematopoietic stem‐cell transplant recipients. In vitro studies have identified letermovir as a potential cytochrome P450 (CYP) 3A inhibitor. Thus, the effect of letermovir on the CYP3A isoenzyme‐specific probe drug midazolam was investigated in a phase 1 trial. Healthy female subjects received single‐dose intravenous (IV; 1 mg) and oral (2 mg) midazolam on days –4 and –2, respectively. Letermovir 240 mg once daily was administered on days 1 to 6, and further single doses of midazolam 1 mg IV and oral midazolam 2 mg were administered on days 4 and 6, respectively. Pharmacokinetics, tolerability, and safety were monitored throughout the trial. Following coadministration with letermovir, the least square means ratio for maximum plasma concentration and area under the plasma concentration–time curve from time 0 to the last measurable concentration was 172.4% and 225.3%, respectively, for oral midazolam, and 105.2% and 146.6%, respectively, for midazolam IV. The area under the plasma concentration–time curve from time 0 to the last measurable concentration ratio of midazolam to 1‐hydroxymidazolam increased slightly in the presence of letermovir following IV (8.8‐13.1; 49% increase) and oral (3.3‐5.3; 59% increase) midazolam. Letermovir reached steady state, on average, by days 5 to 6. All treatments were generally well tolerated. Letermovir demonstrated moderate CYP3A inhibition.
Clinical Pharmacokinetics of Daprodustat: Results of an Absorption, Distribution, and Excretion Study With Intravenous Microtracer and Concomitant Oral Doses for Bioavailability Determination
Authors: Mahar Kelly M. , Caltabiano Stephen , Andrews Susan , Ramanjineyulu Bandi , Chen Liangfu , Young Graeme , Pereira Adrian , Lindsay Alistair C. , van den Berg Frans , Cobitz Alexander R. 
Published: October 2021

AbstractDaprodustat, an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease. This phase 1, nonrandomized, 2‐period, crossover study in 6 healthy men characterized the absorption, distribution, and excretion of daprodustat when administered as oral and intravenous (IV) doses of unlabeled and radiolabeled daprodustat ([14C]‐GSK1278863). Tolerability and pharmacokinetic properties of daprodustat, and its 6 metabolites in the systemic circulation, were also evaluated. The mean recovery of radiolabeled daprodustat was ≈95% by day 5, with the majority in feces and minor renal elimination, indicating that daprodustat and metabolites are primarily eliminated via hepatobiliary and fecal routes. Approximately 40% of total circulating radioactivity in plasma following both IV and oral administration was daprodustat; thus, 60% was attributed to metabolites. It was estimated that ≈80% of daprodustat was absorbed across the gastrointestinal tract, and ≈18% cleared by hepatic extraction. Pharmacokinetics were essentially dose proportional, with moderate (≈66%) oral tablet bioavailability. Following IV administration, daprodustat plasma clearance (19.3 L/h) and volume of distribution (14.6 L) were low, suggesting low tissue distribution outside systemic circulation with likely low penetration into tissues. Daprodustat was generally well tolerated, with no deaths or serious or significant adverse events reported.
Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials
Authors: Leong Ruby , Liu Qi , Li Lingjue , Liu Jiang , Ren Yunzhao R. , Lee Peter , Chuk Meredith , Reaman Gregory , Wang Yaning 
Published: October 2021

Our research supported the dose selection recommendations for adolescents in the US Food and Drug Administration (FDA) Guidance on Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. The FDA Guidance states that for drugs administered as a flat dose in adults and data showing no clinically meaningful effect of body size on drug exposure and toxicity in adults, a minimum body weight threshold may need to be defined to prevent adolescents who have a lower body weight from exceeding adult exposures. Our review of adult population pharmacokinetic analyses of new molecular entities approved for oncology between January 2015 and March 2021 suggested that 40 kg (the approximate median body weight of a 12‐year‐old) is generally the lower end of the body weight range that has no clinically relevant effect on drug pharmacokinetics or safety. The minimum body weight threshold and selection of an appropriate dose for adolescents in relevant adult oncology clinical trials should ultimately be determined based on available data on pharmacokinetics or pharmacodynamics of the investigational drug with consideration of body size effect on drug exposure, toxicity, and efficacy data (if available), the therapeutic index of the drug, and dose‐ and exposure‐response relationships in adults.
Peri‐implant marginal bone loss and systemic statin use: A retrospective cohort pilot study
Authors: Bahrami‐Hessari Behzad , Jansson Leif 
Published: October 2021

AbstractObjectivesThe aim was to analyze clinical parameters of peri‐implantitis in human subjects exposed and non‐exposed to use of systemic statins.Material and methodsThis retrospective cohort pilot study compared patient records of 60 exposed individuals to 196 non‐exposed individuals as of 2011 throughout 2017. Source of records were specialist and general dentistry clinics in Public Dental Service, Stockholm County, Sweden. Extent/severity of peri‐implantitis and peri‐implant bone loss were registered as well as intake of systemic statins. Background variables considered were bleeding on probing, bone‐loss, age, gender, earlier periodontitis, prosthetic quality, and smoking. Stepwise linear and logistic regression analysis at the individual level was adopted in order to study the influence of statin use on the severity of peri‐implantitis and the incidence of peri‐implant bone loss. Results were considered statistically significant at p < 0.05.ResultsPeri‐implant bone loss was significantly correlated to use of statin after compensation for age and sex.ConclusionsThe results render an actual effect of statins on peri‐implant bone loss plausible. Further research is warranted.
Palladium Nanoparticles Hardwired in Carbon Nanoreactors Enable Continually Increasing Electrocatalytic Activity During the Hydrogen Evolution Reaction
Authors: Aygün Mehtap , Guillen‐Soler Melanie , Vila‐Fungueiriño Jose M. , Kurtoglu Abdullah , Chamberlain Thomas W. , Khlobystov Andrei N. , del Carmen Gimenez‐Lopez Maria 
Published: October 2021

AbstractInvited for this month's cover is the group of Maria Gimenez‐Lopez at the University of Santiago de Compostela. The image shows the self‐improving electrochemical activity of palladium nanoparticles hardwired into a graphitic step‐edge for hydrogen production. The Full Paper itself is available at 10.1002/cssc.202101236.
Spatial distribution patterns and predictors of fish beta‐diversity in a large dam‐free tributary from a Neotropical floodplain
Authors: Frota Augusto , Ganassin Maria J. M. , Pacifico Ricardo , Gomes Luiz C. , da Graça Weferson J. 
Published: October 2021

AbstractUnderstanding how and why fish species composition varies between locations through beta‐diversity has received increased interest recently. The physical structure, extension and environmental characteristics along the river basins influence the dispersal of organisms, which ultimately affects metacommunity dynamics and biodiversity patterns. Here, we aimed to identify major breaks delimiting fish assemblages in a large dam‐free river basin on its main channel, which is almost pristine in hidrology, and to evaluate the influence of geo‐climatic variables in the observed beta‐diversity patterns. We used the statistical techniques Species Composition Interpolation (SCI) and Generalized Dissimilarity Modeling (GDM) to analyse beta‐diversity patterns based on georeferenced fish records from the Ivaí River basin. Ichthyofauna units were delimited, estimating the association between geo‐climatic predictors and beta‐diversity. We identified three major breaks delimiting fish assemblages in the Ivaí River basin (i.e. the upper, middle and lower sections). The fish communities were very distinct at the upper and lower sections, while the middle section was recovered as less differentiated. Turnover was the main component contributing to total beta‐diversity, and dissimilarity in fish species composition was moderately associated with geo‐climatic variables. Fish communities from the Ivaí River basin must be associated with niche‐based processes, and we hypothesize that dispersal processes can be equally significant at the basin scale. The investigations may produce insights on strategies for conservation and restoration of degraded rivers, contributing to the long‐term maintenance of fish communities and to the delimitation of new strategic areas for the effective conservation of freshwater biodiversity.
Steric Properties of N‐Heterocyclic Carbenes affect the Performance of Electronic Probes
Authors: Barnett Christopher , Cole Marcus L. , Harper Jason B. 
Published: October 2021

AbstractElectronic probes of ligands, particularly carbenes, are widely used in assessing electronic properties; the results inform the selection of a ligand for a given application. As such, it is important to ensure the data obtained is reliable and unaffected by other factors, such as the steric bulk of the ligand. The effects of such steric factors on two commonly used electronic probes (based on palladium and selenium) are investigated here, with the selenium adduct found to be particularly sensitive. It is hoped that this serves as a cautionary tale to always critically evaluate what a probe is measuring.
Structure‐Proving Syntheses of the Polyenoyltetramic Acids Pyranonigrin J and I
Authors: Drescher Christian , Brückner Reinhard 
Published: October 2021

AbstractThe polyenoyltetramic acids pyranonigrin J (3) and pyranonigrin I (4) had been isolated from Aspergillus niger. Their origins from and roles in biosynthesis as well as the S‐configurations of their stereocenter had been deduced from expression experiments with modifications of the corresponding gene cluster. We corroborated this stereochemical assignment after executing the first total syntheses of both compounds because they had essentially the same specific rotations as their natural counterparts. Our syntheses used the β‐ketothioester 18 as a conjunctive reagent. It was combined with the l‐serine derivatives (S)‐19 or (S)‐21 (“Western building blocks”), respectively, through aminolyses. Stille couplings with the stannane 13 (“Eastern building block”) followed. The resulting β‐ketoamides (S)‐11 and (S)‐12 underwent desilylative Lacey‐Dieckmann cyclizations when exposed to 8 equiv. of Bu4NF. They rendered the polyenoyltetramic acids (S)‐26 [acidolysis: → (S)‐3] and (S)‐4, respectively.
Identification of biomarkers related to glycolysis with weighted gene co‐expression network analysis in oral squamous cell carcinoma
Authors: Zhou Xiongming , Xue Danfeng , Qiu Jiaxuan 
Published: October 2021

AbstractBackgroundOral squamous cell carcinoma (OSCC) is the most common tumor in the oral cavity and maxillofacial region. Increasing evidence suggests that aerobic glycolysis plays an important role in the occurrence, development, and prognosis of OSCC. Therefore, the identification of biomarkers related to glycolysis in OSCC represents considerable potential for improving its treatment.MethodsIn the present study, a single‐sample gene‐set enrichment analysis (ssGSEA) algorithm with weighted gene co‐expression network analysis (WGCNA) were used to quantify the degree of glycolysis and identify key modules with the greatest correlation with glycolysis.ResultsGlycolytic scores significantly correlated with prognosis. In the key module 5 HUB genes were finally selected, which displayed a robust predictive effect. The expressions of key genes were associated with glycolysis.ConclusionsThe research comprehensively analyzed the glycolysis of OSCC and identified several biomarkers related to glycolysis. These biomarkers may represent potential therapeutic targets for future OSCC therapy.
Large granular lymphocytosis: A novel association with immunotherapy
Authors: Nedumannil Rithin , Juneja Surender 
Published: October 2021

AbstractAlthough reactive large granular lymphocytosis due to diverse etiologies is not an uncommon finding in clinical practice, isolated natural killer (NK)‐cell lymphocytosis is unusual and its association with immunotherapy has not been described thus far. We provide a brief analysis of a patient with this unique hematological corollary of immunotherapy being increasingly used in the setting of both solid organ and hematological malignancies, and highlight this as an additional differential to consider in the diagnosis of large granular lymphocytosis. Also explored is the importance of recognizing and monitoring the potential hematological manifestations of experimental immunotherapies, as well as the possible implicated mechanisms of action. It is hypothesized that quantification of large granular lymphocytosis may potentially be used as a surrogate marker of therapeutic efficacy in this setting.
An evaluation of Turkey's health tourism policies using a social network analysis approach
Authors: Uygun Meltem 
Published: October 2021

AbstractDespite the health tourism sector's rapid growth in the past decade due to globalisation, there is little research analysing countries' health tourism policies. This study aimed to examine the relationships between stakeholders in the health tourism sector in Turkey in the context of Turkey's health tourism policies. This study connects theory and practice in multidisciplinary sectors, including health, tourism, and business, through an evaluation of major issues from a health management perspective. Social network analysis was used to assess the role of 107 stakeholders in Ankara and determine the extent of weak and strong ties among them. Issues confronting these stakeholders and the obstacles they faced in practice were also identified. The study found that, the relevant stakeholders faced comprehensive sectoral deficiencies and issues in building positive relationships. Governmental stakeholders as policymakers need to develop effective strategies to improve stakeholder collaboration and encourage greater inclusiveness through better‐targeted health tourism policies. The study contributes to social network theory, resource dependency theory, and stakeholder theory, and is, to our knowledge, the first study to use social network analysis to examine the role of stakeholders in the health tourism sector.
Vitamin D and Skeletal Muscle: Current Concepts From Preclinical Studies
Authors: Girgis Christian M. , Brennan‐Speranza Tara C. 
Published: October 2021

ABSTRACTMuscle weakness has been recognized as a hallmark feature of vitamin D deficiency for many years. Until recently, the direct biomolecular effects of vitamin D on skeletal muscle have been unclear. Although in the past, some reservations have been raised regarding the expression of the vitamin D receptor in muscle tissue, this special issue review article outlines the clear evidence from preclinical studies for not only the expression of the receptor in muscle but also the roles of vitamin D activity in muscle development, mass, and strength. Additionally, muscle may also serve as a dynamic storage site for vitamin D, and play a central role in the maintenance of circulating 25‐hydroxy vitamin D levels during periods of low sun exposure. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.