bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Multiple Drug Administration from Depot by Applying Pharmacokinetic Concepts
Authors:   Department of Mathematical Analysis and Differential Equations, Faculty of Applied Mathematics and Informatics, Technical University – Sofia, Prodanova Krasimira
Published: December 2020

For the multiple drug administration from therapeutic reasons it is important to maintain the concentration in the blood plasma in an appropriate range. In the present paper an optimization approach is developed to determine drug dosage regimen to achieve the desired plasma concentrations after application from depot, i.e. oral, muscular, subcutant. The developed methodology allows the optimization of both the dose and the dosage interval. Performance of the developed methodology is evaluated by computing bias and precision of the estimated trough and peak drug concentrations that are reached after dosage regimen determinations. This article focuses on an optimal impulsive control of compartment model to individualise dosage regimens of Amikacin in the context of extended dosage intervals. Amikacin is an aminoglycoside antibiotic used to treat various bacterial infections.
Computerized Neuropsychological Test Battery CogniSoft for Assessment of Cognition in Patients with Multiple Sclerosis
Authors:   Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 105, Sofia 1113, Bulgaria, Todorova Lyudmila , Ignatova Valentina ,   Clinic of Neurology, Multiprofile Hospital for Active Treatment – National Heart Hospital, 65 Konyovitsa Str., Sofia 1309, Bulgaria, Surchev Jivko ,   Department of Neurosurgery, St. Ivan Rilski University Hospital – Medical University of Sofia, 15 Akad. Ivan Geshov Str., Sofia 1431, Bulgaria
Published: December 2020

Cognitive dysfunction is a leading cause of disability in multiple sclerosis (MS) and is associated with unemployment, need of assistance with daily activities and poor quality of life. The introduction of neuropsychological testing and monitoring of cognitive status as part of the overall evaluation of MS patients in parallel with clinical and paraclinical parameters is highly recommended. Recent studies have demonstrated a better perception and preference for computerized cognitive tests than classic variants, with no significant difference in results. In accordance with global trends, a bilingual computer system CogniSoft for assessment and rehabilitation of cognitive status in persons with MS has been developed, including: 1) a set of diagnostic tests for evaluation of memory and executive functions based on the nature of Brief International Cognitive Assessment for MS (BICAMS); 2) a set of games for cognitive rehabilitation. Questionnaire for depression (Beck Depression Inventory – BDI-II) will be filled before conduction of the neuropsychological tests for differentiation of possible depression which could interfere with the results. The CogniSoft information system will incorporate two approaches for evaluation of neuropsychological results which will allow early detection of cognitive impairments in these patients, which will initiate timely cognitive rehabilitation.
Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia
Authors: Gregorova Michaela , Morse Daniel , Brignoli Tarcisio , Steventon Joseph , Hamilton Fergus , Albur Mahableshwar , Arnold David , Thomas Matthew , Halliday Alice , Baum Holly , Rice Christopher , Avison Matthew B , Davidson Andrew D , Santopaolo Marianna , Oliver Elizabeth , Goenka Anu , Finn Adam , Wooldridge Linda , Amulic Borko , Boyton Rosemary J , Altmann Daniel M , Butler David K , McMurray Claire , Stockton Joanna , Nicholls Sam , Cooper Charles , Loman Nicholas , Cox Michael J , Rivino Laura , Massey Ruth C
Published: December 2020

Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient’s persistent symptoms and radiological changes.
Distribution and Abundance of the Eastern Canada – West Greenland Bowhead Whale Population Based on the 2013 High Arctic Cetacean Survey
Authors: Doniol-Valcroze Thomas , Gosselin Jean-François , Pike Daniel G. , Lawson Jack W. , Asselin Natalie C. , Hedges Kevin J. , Ferguson Steven H.
Published: December 2020

The hunting of bowhead whales (Balaena mysticetus) is an integral part of Inuit culture. An up-to-date abundance estimate of the entire Eastern Canada – West Greenland (EC-WG) bowhead population is necessary to support sustainable management of this harvest. The High Arctic Cetacean Survey (HACS) was conducted in August 2013, primarily to update abundance estimates for known stocks of Baffin Bay narwhal (Monodon monoceros). As the ranges of narwhal and bowhead largely overlap, the survey area was expanded to cover the summer range of bowhead whales. Bowhead whale abundance was estimated using 3 aircraft to cover the large survey area within a short time frame. Distance sampling methods were used to estimate detection probability away from the track line. Double platform with mark-recapture methods were used to correct for the proportion of whales missed by visual observers on the track line (perception bias). Abundance in Isabella Bay, an area known for high bowhead density, was estimated using density surface modelling to account for its complex shape and uneven coverage. Estimates were corrected for availability bias (whales that were not available for detection because they were submerged when the aircraft passed overhead) using a recent analysis of satellite-linked time depth recorders transmitting information on the diving behaviour of bowhead whales in the study area in August of the same survey year. The fully corrected abundance estimate for the EC-WG bowhead whale population was 6,446 (95% CI: 3,838–10,827). Possible sources of uncertainty include incomplete coverage and the diving behaviour of bowhead whales. These results confirm earlier indications that the EC-WG stock is continuing to recover from past overexploitation.
DHA content in milk and biohydrogenation pathway in rumen: a review
Authors: Huang Guoxin , Zhang Yangdong , Xu Qingbiao , Zheng Nan , Zhao Shengguo , Liu Kaizhen , Qu Xueyin , Yu Jing , Wang Jiaqi
Published: December 2020

Docosahexaenoic acid (DHA) is an essential human nutrient that may promote neural health and development. DHA occurs naturally in milk in concentrations that are influenced by many factors, including the dietary intake of the cow and the rumen microbiome. We reviewed the literature of milk DHA content and the biohydrogenation pathway in rumen of dairy cows aim to enhance the DHA content. DHA in milk is mainly derived from two sources:α-linolenic acid (ALA) occurring in the liver and consumed as part of the diet, and overall dietary intake. Rumen biohydrogenation, the lymphatic system, and blood circulation influence the movement of dietary intake of DHA into the milk supply. Rumen biohydrogenation reduces DHA in ruminal environmental and limits DHA incorporation into milk. Thefat-1gene may increase DHA uptake into the body but this lacks experimental confirmation. Additional studies are needed to define the mechanisms by which different dietary sources of DHA are associated with variations of DHA in milk, the pathway of DHA biohydrogenation in the rumen, and the function of thefat-1gene on DHA supply in dairy cows.
Evolution ofWolbachiamutualism and reproductive parasitism: insight from two novel strains that co-infect cat fleas
Authors: Driscoll Timothy P. , Verhoeve Victoria I. , Brockway Cassia , Shrewsberry Darin L. , Plumer Mariah , Sevdalis Spiridon E. , Beckmann John F. , Krueger Laura M. , Macaluso Kevin R. , Azad Abdu F. , Gillespie Joseph J.
Published: December 2020

Wolbachiae are obligate intracellular bacteria that infect arthropods and certain nematodes. Usually maternally inherited, they may provision nutrients to (mutualism) or alter sexual biology of (reproductive parasitism) their invertebrate hosts. We report the assembly of closed genomes for two novel wolbachiae,wCfeT andwCfeJ, found co-infecting cat fleas (Ctenocephalides felis) of the Elward Laboratory colony (Soquel, CA, USA).wCfeT is basal to nearly all describedWolbachiasupergroups, whilewCfeJ is related to supergroups C, D and F. Both genomes contain laterally transferred genes that inform on the evolution ofWolbachiahost associations.wCfeT carries the Biotin synthesis Operon of Obligate intracellular Microbes (BOOM); our analyses reveal five independent acquisitions of BOOM across theWolbachiatree, indicating parallel evolution towards mutualism. Alternately,wCfeJ harbors a toxin-antidote operon analogous to thewPipcinABoperon recently characterized as an inducer of cytoplasmic incompatibility (CI) in flies.wCfeJcinBand three adjacent genes are collectively similar to large modular toxins encoded in CI-like operons of certainWolbachiastrains andRickettsiaspecies, signifying that CI toxins streamline by fission of large modular toxins. Remarkably, theC.felisgenome itself contains two CI-like antidote genes, divergent fromwCfeJcinA, revealing episodic reproductive parasitism in cat fleas and evidencing mobility of CI loci independent of WO-phage. Additional screening revealed predominant co-infection (wCfeT/wCfeJ) amongstC.feliscolonies, though fleas in wild populations mostly harborwCfeT alone. Collectively, genomes ofwCfeT,wCfeJ, and their cat flea host supply instances of lateral gene transfers that could drive transitions between parasitism and mutualism.
Musical sophistication explains a good deal of cognitive performance. A cross-sectional study of musicians and non-musicians
Authors: Porflitt Felipe , Rosas Ricardo
Published: December 2020

Musical sophistication is a psychometric construct that can be measured both in people with musical training and without training. Through backgrounds related to musical activities in their lifetime, and other indicators referring to their current events, the person’s musical sophistication can be estimated with a relatively high level of reliability (Cronbach’s α =.78). In turn, few studies have covered the relationships between variables of this type and cognitive performance, leaving an area of research with little evidence. This study explores the relationship between musical sophistication and cognition, taking a sample of 35 musicians and 35 non-musicians (N=70). The objective was to determine to what extent musical sophistication explains cognitive performance. The Ollen Musical Sophistication Index (Ollen 2006) was used to measure this variable, and a battery of tests enabled the measurement of cognitive performance, which considered verbal and visual-spatial working memory, inhibition, flexibility, a go/no-go test, processing speed, fluid intelligence, and divided attention. Exploratory factor analysis was run, showing two factors for cognition variables. Then regression analyses were run for factors 1 and 2, and both collapsed. The results show that 6 out of 8 cognitive variables correlate positively with musical sophistication, explaining 30% of cognitive performance, after controlling for demographic variables.
Prevalence and Factors Associated With Osteoporosis and Bone Mineral Density Testing in Psoriatic Arthritis
Authors: Kwok Timothy S. H. , Sutton Mitchell , Ye Justine Yang , Pereira Daniel , Chandran Vinod , Gladman Dafna D.
Published: December 2020

Objective

To determine bone mineral density (BMD) in psoriatic arthritis (PsA) patients, factors associated with undergoing BMD testing, and the effect of PsA clinical activity on BMD.

Methods

Patients attending the University of Toronto PsA Clinic with BMD testing results from cohort inception to January 2019 were included. Descriptive statistics summarized lumbar spine, femoral neck, and total hip T scores. Cox proportional hazards regression identified predictors for BMD testing. Logistic regression analysis determined odds of having normal (T score −1.0 or more) versus osteoporotic‐range BMD (T score −2.5 or less). A multistate model determined factors associated with BMD state changes over time.

Results

Of the 1,479 patients, 214 had BMD tests performed. The mean ± SD T scores at the lumbar spine, femoral neck, and total hip were −0.30 ± 0.32, −1.10 ± 1.04, and −0.45 ± 0.42, respectively. Osteopenia and osteoporosis occurred in 45.27% and 12.94% of patients. Increasing age, menopause, elevated acute‐phase reactants, and biologics, methotrexate, and systemic glucocorticoids use were associated with a higher chance of undergoing BMD testing. Increased body mass index (BMI) and biologics use were associated with a lower chance of having osteoporotic‐range BMD test results. In multistate analysis, polyarthritis may portend lower BMD results over time, although this did not achieve statistical significance due to low patient numbers.

Conclusion

The prevalence of osteopenia and osteoporosis in the PsA cohort was similar to that of the general population. Clinicians are using osteoporosis risk factors and PsA disease severity markers to select patients for BMD testing. Polyarticular disease may portend worse BMD test results. Biologic use and increased BMI appear to have a protective effect.
On the trail of blood doping—microRNA fingerprints to monitor autologous blood transfusions in vivo
Authors: Mussack Veronika , Wittmann Georg , Pfaffl Michael W.
Published: December 2020

Autologous blood doping refers to the illegal re‐transfusion of any quantities of blood or blood components with blood donor and recipient being the same person. The re‐transfusion of stored erythrocyte concentrates is particularly attractive to high‐performance athletes as this practice improves their oxygen capacity excessively. However, there is still no reliable detection method available. Analyzing circulating microRNA profiles of human subjects that underwent monitored autologous blood transfusions seems to be a highly promising approach to develop novel biomarkers for autologous blood doping. In this exploratory study, we randomly divided 30 healthy males into two different treatment groups and one control group and sampled whole blood at several time points at baseline, after whole blood donation and after transfusion of erythrocyte concentrates. Hematological variables were recorded and analyzed following the adaptive model of the Athlete Biological Passport. microRNA profiles were examined by small RNA sequencing and comprehensive multivariate data analyses, revealing microRNA fingerprints that reflect the sampling time point and transfusion volume. Neither individual microRNAs nor a signature of transfusion‐dependent microRNAs reached superior sensitivity at 100% specificity compared to the Athlete Biological Passport (≤11% 6 h after transfusion versus ≤44% 2 days after transfusion). However, the window of autologous blood doping detection was different. Due to the heterogenous nature of doping, with athletes frequently combining multiple medications in order to both gain a competitive advantage and interfere with known testing methods, the true applicability of the molecular signature remains to be validated in real anti‐doping testings.
The Development of a Fluorescence‐Based Competitive Assay Enabled the Discovery of Dimeric Cyclic Peptide Modulators of Ubiquitin Chains
Authors: Vamisetti Ganga B. , Meledin Roman , Nawatha Mickal , Suga Hiroaki , Brik Ashraf
Published: December 2020

Development of modulators targeting specific interactions of ubiquitin‐based conjugates with their partners is a formidable task since it requires a suitable screening assay and homogeneous ubiquitin conjugates. We developed a novel high‐throughput strategy for screening ligands for Lys48‐linked tetraubiquitin chain in a relatively simple, fast, and affordable manner. This approach combined with a state‐of‐the‐art toolbox of chemical protein synthesis and a specially optimized Cys deprotection protocol enabled us to design highly potent, Lys48‐linked tetraubiquitin chain selective “next generation” dimeric peptide modulators. The dimeric peptide exhibited cancer cell permeability and induced cell death with higher efficiency compared to its monocyclic analogue. These features make our dimeric peptide a promising candidate for further studies using in vivo models. Our assay can be adopted for other various ubiquitin chains in their free or anchored forms as well as conjugates for Ub‐like modifiers.
Growth of Colloidal Nanocrystals by Liquid‐Like Coalescence**
Authors: Yuan Bin , Cademartiri Ludovico
Published: December 2020

We here describe, model, and predict the growth kinetics of amine‐capped PbS colloidal nanoparticles in the absence of supersaturation. The particles grow by coalescence rather than by Ostwald ripening. A comparison of different models indicates that the effective activation energy of coalescence (67.65 kJ mol−1) is associated with two terms: a term proportional to the contact area between the ligand shells of two colliding particles, and a constant term. Our Brownian dynamics simulations show (i) how the remarkably low activation energy (or large rate constants) are most likely due to the large difference in size between the particles and their mean free path of diffusion, and (ii) how the low polydispersity is the likely result of the suppression of collision rates between rare populations due to crowding. The model successfully predicts the growth kinetics of nanoparticles, therefore enabling the precise control of the average particle size without the need of supersaturation.
Structurally Modelling the 2‐His‐1‐Carboxylate Facial Triad with a Bulky N,N,O Phenolate Ligand
Authors: Monkcom Emily C. , de Bruin Daniël , de Vries Annemiek J. , Lutz Martin , Ye Shengfa , Klein Gebbink Robertus J. M.
Published: December 2020

We present the synthesis and coordination chemistry of a bulky, tripodal N,N,O ligand, ImPh2NNOtBu (L), designed to model the 2‐His‐1‐carboxylate facial triad (2H1C) by means of two imidazole groups and an anionic 2,4‐di‐tert‐butyl‐subtituted phenolate. Reacting K‐L with MCl2 (M = Fe, Zn) affords the isostructural, tetrahedral non‐heme complexes [Fe(L)(Cl)] (1) and [Zn(L)(Cl)] (2) in high yield. The tridentate N,N,O ligand coordination observed in their X‐ray crystal structures remains intact and well‐defined in MeCN and CH2Cl2 solution. Reacting 2 with NaSPh affords a tetrahedral zinc thiolate complex, [Zn(L)(SPh)] (4), that is relevant to isopenicillin N synthase (IPNS) biomimicry. Cyclic voltammetry studies demonstrate the ligand's redox non‐innocence, where phenolate oxidation is the first electrochemical response observed in K‐L, 2 and 4. However, the first electrochemical oxidation in 1 is iron‐centred, the assignment of which is supported by DFT calculations. Overall, ImPh2NNOtBu provides access to well‐defined mononuclear, monoligated, N,N,O‐bound metal complexes, enabling more accurate structural modelling of the 2H1C to be achieved.
Synthesis, Characterization of Spirocyclic λ3‐Iodanes and Their Application to Prepare 4,1‐Benzoxazepine‐2,5‐diones and 1,3‐Diynes
Authors: Sun Xu , Guo Xiao‐Qiang , Chen Lian‐Mei , Kang Tai‐Ran
Published: December 2020

Herein, a [3+2] cycloaddition of aza‐oxyallylic cations with ethynylbenziodoxolones for synthesis of new λ3‐iodanes containing spirocyclic 4‐oxazolidinone has been developed. This cyclic λ3‐iodanes display stability in air and excellent solubility in organic solvent. Using them as substrate, both the 4,1‐benzoxazepine‐2,5‐diones and symmetrical 1,3‐diynes derivatives were afforded in high yield under copper(I)‐catalyzed conditions.
Cationic Bismuth Aminotroponiminates: Charge Controls Redox Properties
Authors: Hanft Anna , Radacki Krzysztof , Lichtenberg Crispin
Published: December 2020

The behavior of the redox‐active aminotroponiminate (ATI) ligand in the coordination sphere of bismuth has been investigated in neutral and cationic compounds, [Bi(ATI)3] and [Bi(ATI)2Ln][A] (L=neutral ligand; n=0, 1; A=counteranion). Their coordination chemistry in solution and in the solid state has been analyzed through (variable‐temperature) NMR spectroscopy, line‐shape analysis, and single‐crystal X‐ray diffraction analyses, and their Lewis acidity has been evaluated by using the Gutmann–Beckett method (and modifications thereof). Cyclic voltammetry, in combination with DFT calculations, indicates that switching between ligand‐ and metal‐centered redox events is possible by altering the charge of the compounds from 0 in neutral species to +1 in cationic compounds. This adds important facets to the rich redox chemistry of ATIs and to the redox chemistry of bismuth compounds, which is, so far, largely unexplored.
Highly Efficient Iridium‐Catalyzed Production of Hydrogen and Lactate from Glycerol: Rapid Hydrogen Evolution by Bimetallic Iridium Catalysts
Authors: Cheong Yeon‐Joo , Sung Kihyuk , Kim Jin‐A , Kim Yu Kwon , Jang Hye‐Young
Published: December 2020

Mono‐ and bimetallic iridium complexes involving novel triscarbene ligands were synthesized and applied to the dehydrogenation of biomass‐derived glycerol. This resulted in affording hydrogen and lactate with the excellent turnover number (TON; 3,240,000) and turnover frequency (TOF; 162,000 h–1). The triscarbene ligand in a single frame allowed the formation of bimetallic iridium complexes. This induced the cooperative effect of two iridium ions and rendered excellent TONs and TOFs in the production of hydrogen and lactate.
2D and 3D Ruthenium Nanoparticle Covalent Assemblies for Phenyl Acetylene Hydrogenation
Authors: Min Yuanyuan , Leng Faqiang , Machado Bruno F. , Lecante Pierre , Roblin Pierre , Martinez Hervé , Theussl Thomas , Casu Alberto , Falqui Andrea , Barcenilla María , Coco Silverio , Martínez Beatriz María Illescas , Martin Nazario , Axet M. Rosa , Serp Philippe
Published: December 2020

The bottom‐up covalent assembly of metallic nanoparticles (NP) represents one of the innovative tools in nanotechnology to build functional heterostructures, with the resulting assemblies showing superior collective properties over the individual NP for a broad range of applications. The ability to control the dimensionality of the assembly is one of the major challenges in designing and understanding these advanced materials. Here, two new organic linkers were used as building blocks in order to guide the organization of Ru NP into two‐ or three‐dimensional covalent assemblies. The use of a hexa‐adduct functionalized C60 leads to the formation of 3D networks of 2.2 nm Ru NP presenting an interparticle distance of 3.0 nm, and the use of a planar carboxylic acid triphenylene derivative allows the synthesis of 2D networks of 1.9 nm Ru NP with an interparticle distance of 3.1 nm. The Ru NP networks were found to be active catalysts for the selective hydrogenation of phenylacetylene, reaching good selectivity toward styrene. Overall, we demonstrated that catalyst performances are significantly affected by the dimensionality (2D vs. 3D) of the heterostructures, which can be rationalize based on confinement effects.
Carbenoid‐Mediated Formation and Activation of Element‐Element and Element–Hydrogen Bonds
Authors: Dilchert Katharina , Scherpf Thorsten , Gessner Viktoria H.
Published: December 2020

The application of the silyl‐substituted Li/Cl carbenoid RR'C(Li)Cl (1) [with R = Ph2P(S), R' = SiMe3] in the dehydrocoupling of group 14 element hydrides is reported. While silanes only yield product mixtures, selective E–E bond formation was observed for germanes and stannanes. In case of the tin compounds, also aliphatic stannanes could be successfully coupled to the corresponding distannanes. This reactivity is in contrast to that reported for BH3, which preferentially undergoes B–H addition to the carbenoid carbon atom via borate formation. Formation of a borate intermediate is also assumed to be the initial step in the reaction of 1 with phosphinoborane CatB‐PPh2 (Cat = catecholato), which results in the generation of diphosphine Ph4P2 via chlorotrimethylsilane elimination and formation of a 1,1'‐diborylated carbanion.
Versatile Coordination Behavior of the Asymmetric Bis(3‐mesityl‐pyrazol‐1‐yl)(5‐mesitylpyrazol‐1‐yl) Hydroborate Ligand towards Late 3 d M2+ Ions
Authors: Müller Lars , Nadurata Vincent L. , Cula Beatrice , Hoof Santina , Herwig Christian , Limberg Christian
Published: December 2020

Bearing in mind the potential which tris(pyrazolyl) hydroborate ligands have demonstrated in various different fields of coordination chemistry, the behavior of a more rarely employed representative, namely bis(3‐mesitylpyrazol‐1‐yl)(5‐mesitylpyrazol‐1‐yl) hydroborate (TpMes,H*), towards a series of divalent metal ions has been investigated. Thus, the synthesis of two new heteroleptic metal chlorido [TpMes,H*MCl] complexes, 2, (Mn2+, 2‐a, and Cu2+, 2‐e) are described, which correspond to the typical precursor compounds that would be needed for subsequent research. Structural and spectroscopic properties of the two new and four published members of this series (M=Fe2+, 2‐b, Co2+, 2‐c, Ni2+, 2‐d, Zn2+, 2‐f) are discussed in detail for the solid and solution states. Furthermore, synthetic routes to five homoleptic [(TpMes,H*)2M] complexes, 3, bearing Mn2+, 3‐a, Fe2+, 3‐b, Co2+, 3‐c, Ni2+, 3‐d, and Cu2+, 3‐e, ions as well as an alternative preparation method for [(κ2‐TpMes,H*)2Zn], 3‐f, are described. Their structures and spectroscopic parameters are compared to those of their heteroleptic counterparts. Additionally, the complex [(TpH,Mes*)2Cu], 4, is reported, representing the second example of a complex with the (3‐mesitylpyrazol‐1‐yl)bis(5‐mesitylpyrazol‐1‐yl) hydroborate ligand (TpH,Mes*).
Multibranched Calix[4]arene‐Based Sensitizers for Efficient Photocatalytic Hydrogen Production
Authors: Manfredi Norberto , Decavoli Cristina , Boldrini Chiara Liliana , Dolla Tarekegn Heliso , Faroldi Federica , Sansone Francesco , Montini Tiziano , Baldini Laura , Fornasiero Paolo , Abbotto Alessandro
Published: December 2020

In the field of direct production of hydrogen from solar energy and water, photocatalytic methods hold great potential especially when metal‐free molecular components are preferred. In this work, we have developed a new class of calix[4]arene‐based molecular photosensitizers to be used as antenna systems in the photocatalytic production of hydrogen. The structure of the dyes has a typical donor‐π‐acceptor molecular architecture where a calix[4]arene scaffold is used as an embedded donor. The new materials have been fully characterized in their optical, electrochemical, and photocatalytic properties. The properties conferred by the calix[4]arene donor afforded twice larger performances compared to the corresponding linear system though showing similar quantitative optical properties. The new molecular design paves the way to a new strategy for photocatalytic hydrogen production where the calix[4]arene scaffold can afford more efficient systems and can offer the potential for host‐guest supramolecular effects.
Click‐Connected 2‐(Hydroxyimino)aldehydes for the Design of UV‐Responsive Functional Molecules
Authors: D'Acunzo Francesca , Carbonaro Linda , Cort Antonella Dalla , Di Sabato Antonio , Filippini Dario , Leonelli Francesca , Mancini Laura , Gentili Patrizia
Published: December 2020

Click chemistry is used to functionalize simple lipophilic and water‐soluble molecules, a complex PEGylated phospholipid (DSPE‐PEG2000), and two benzylic substrates with the 2‐(hydroxyimino)aldehyde (HIA) group. To this end, two terminal alkynes bearing the HIA moiety were synthesized and coupled to different azides through copper(I)‐catalyzed azide alkyne cycloaddition (CuAAC). Norrish–Yang photoisomerization (λ= 365 nm, LED source) is successfully obtained, with no interference by the triazole linker, except when the forbidden n‐π* carbonyl transition is screened by a remote substituent such as salicylaldehyde. UV‐Vis spectrometry suggests a specific interaction of HIAs with Cu(II), whereas no such evidence is found with Cu(I). We thereby show that the CuAAC methodology can be used successfully to obtain HIA‐based UV‐responsive hydrophilic or lipophilic ligands, phospholipidic components for the construction of liposomes, and macrocycle precursors.
N1‐ and N3‐Arylations of Hydantoins Employing Diaryliodonium Salts via Copper(I) Catalysis at Room Temperature
Authors: Abha Saikia Raktim , Barman Dhiraj , Dutta Anurag , Jyoti Thakur Ashim
Published: December 2020

Copper(I)‐catalyzed N‐arylation (both N1‐ and N3‐) of hydantoins with diaryliodonium salts as aryl partners at room temperature is reported. The transformation allows diverse scopes on both hydantoins and diaryliodonium salts delivering functionalized N3‐arylated products under mild reaction conditions. The presence of hydrogens at C5‐ and N1‐ position of the hydantoin does not lead to other side products. Chiral hydantoins can also be synthesized via this methodology. Sterically complicated ortho‐substituted diaryliodonium salts are tolerated and delivered challenging ortho‐arylated products. In addition, this strategy can also be effectively extended to N1‐arylation of hydantoins.
I2‐Promoted Direct C−H Sulfenylation of Isoquinolin‐1(2H)‐ones with Sulfonyl Chlorides
Authors: Yang Cai‐Yun , Li Xia , Liu Bo , Huang Guo‐Li
Published: December 2020

A simple, efficient, and green method for the iodine‐promoted regioselective C‐4 sulfenylation of isoquinolin‐1(2H)‐ones using commercially available aryl sulfonyl chlorides as the sulfur source was described under metal‐ and solvent‐free conditions. The reaction proceeded smoothly under simple conditions to obtain 4‐arylthioisoquinolin‐1(2H)‐ones in moderate to good yields, and showed high regioselectivity, broad substrate scope, and good functional group tolerance. A radical reaction mechanism involving ArS. radicals as key intermediates is proposed for the present transformation.
Role of Lipophilicity in the Activity of Hexameric Cyclic Peptoid Ion Carriers
Authors: Schettini Rosaria , Tosolini Massimo , ur Rehman Jawad , Shah Muhammed Raza , Pierri Giovanni , Tedesco Consiglia , Della Sala Giorgio , De Riccardis Francesco , Tecilla Paolo , Izzo Irene
Published: December 2020

Two families of hexameric cyclic peptoids decorated with linear N‐alkyl and alternated N‐alkyl/N‐benzyl side chains (2 a–d and 3 a–c, respectively) were designed and synthesized in order to correlate their logP values (from 2.55 to 6.83) to their ionophoric activities. The present contribution confirms the general ability of hexameric cyclic peptoids to behave as efficient cation carriers, corroborates their preference for Na+ ion, among the tested alkali metals, and suggests a Na+/H+ antiport transport mechanism (rate limited by the transport of the proton) for these new ionophores. Our observations indicate that in order to attain an efficient ionophoric activity, a narrow range of liphophilicity is required (4<logP<5). Moreover, to gain information on the solid state stucture of ionophoric cyclic peptoids with linear N‐side chains, X‐ray crystallographic studies were performed on exemplar compound 2 a. Crystal structure of compound 2 a confirms the tendency of ionophoric cyclopeptoids with linear N‐side chains to form layered assemblies.
Rigid Multidimensional Alkoxyamines: A Versatile Building Block Library
Authors: Matt Yannick , Wessely Isabelle , Gramespacher Lisa , Tsotsalas Manuel , Bräse Stefan
Published: December 2020

Since the discovery of the “living” free‐radical polymerization, alkoxyamines were widely used in nitroxide‐mediated polymerization (NMP). Most of the known alkoxyamines bear just one functionality with only a few exceptions bearing two or more alkoxyamine units. Herein, we present a library of novel multidimensional alkoxyamines based on commercially available, rigid, aromatic core structures. A versatile approach allows the introduction of different sidechains which have an impact on the steric hindrance and dissociation behavior of the alkoxyamines. The reaction to the alkoxyamines was optimized by implementing a mild and reliable procedure to give all target compounds in high yields. Utilization of biphenyl, p‐terphenyl, 1,3,5‐triphenylbenzene, tetraphenylethylene, and tetraphenyl‐methane results in linear, trigonal, square planar, and tetrahedral shaped alkoxyamines. These building blocks are useful initiators for multifold NMP leading to star‐shaped polymers or as a linker for the nitroxide exchange reaction (NER), to obtain dynamic frameworks with a tunable crosslinking degree and self‐healing abilities.
Photochemical Reaction of N,N‐Dimethylanilines with N‐Substituted Maleimides Utilizing Benzaldehyde as the Photoinitiator
Authors: Nikitas Nikolaos F. , Theodoropoulou Maria A. , Kokotos Christoforos G.
Published: December 2020

Photoorganocatalysis constitutes a powerful domain of photochemistry and organic synthesis. The scaffold of pyrrolo[3,4‐c]quinolinoles exhibits interesting and potent inhibition against various enzymes, making them really promising pharmaceutical targets. Herein, we describe a photochemical methodology for the reaction of N,N‐dimethylanilines with N‐substituted maleimides, utilizing benzaldehyde as the photoinitiator. A variety of substituted N,N‐dimethylanilines and N‐substituted maleimides were converted into the corresponding adducts in moderate to high yields.
First‐ and second‐trimester uterine artery pulsatility index as a combination factor in predictive diagnosis of pregnancy‐induced hypertension
Authors: Dash Sonali S. , Jena Pramila , Khuntia Swetaparna , Pathak Mona , Rath Sudhanshu K.
Published: December 2020

Objective

Hypertensive disorder of pregnancy is a major cause of fetal and maternal morbidity and mortality. The current approach for pregnancy‐induced hypertension (PIH) screening is complex and expensive. The present prospective cohort study assesses the advantage of combining first‐ and second‐trimester uterine artery pulsatility index (UAPI) for predictive diagnosis of PIH.

Methods

A total of 151 prenatal cases in their first trimester were studied and followed up till delivery. The mean UAPI was calculated for the first and second trimesters during the nuchal translucency and anomaly scans. Receiver operating characteristic analysis was used to calculate the cut‐off of UAPI for first‐trimester, second‐trimester, and both trimesters combined.

Results

Twenty‐seven (17.9%) pregnant women developed PIH. Mean ± SD UAPI values for first and second trimesters were 1.92 ± 0.60 and 1.23 ± 0.36, respectively. The cut‐offs for abnormal UAPI were ≥2.51, ≥1.32, and ≥1.91 for first trimester, second trimester, and both trimesters combined, respectively. The sensitivity and specificity of UAPI in predictive diagnosis of PIH were 82% and 95% for first trimester, 93% and 85% for the second trimester, and 93% and 98% for both trimesters combined.

Conclusion

Combining UAPI of first and second trimesters improves the predictive diagnosis of PIH, which can be carried out during the nuchal translucency and anomaly scans without imparting extra cost to the patient.
Synthesis of Tricyclic Laddersiloxane with Various Ring Sizes (Bat Siloxane)
Authors: Chaiprasert Thanawat , Liu Yujia , Intaraprecha Pa‐kwan , Kunthom Rungthip , Takeda Nobuhiro , Unno Masafumi
Published: December 2020

A new synthetic method for tricyclic laddersiloxanes, ladder‐type silsesquioxanes with defined structures, is developed based on intramolecular cyclization of hydrosilyl‐functionalized cyclic siloxanes. This method enables the construction of unprecedented laddersiloxanes with various ring sizes. Herein, the preparation of tricyclic laddersiloxanes containing 6‐8‐6‐, 8‐8‐8‐, or 12‐8‐12‐membered‐ring systems is reported. These products can be considered as bat‐shape siloxanes, owing to their rigid inorganic siloxane body with flexible oligosiloxane “wings” as side rings. The synthesized compounds are potential building blocks for well‐defined nanomaterials, porous materials, and host molecules.
Rotaxane‐Based Difunctional Nitrile N‐Oxide Crosslinker: Synthesis and Direct Introduction of Movable Crosslinking Points into Ethylene‐Propylene‐Butadiene Monomer (EPDM) Rubber
Authors: Sogawa Hiromitsu , Tsutsuba Toyokazu , Sakiyama Naoto , Ikeda Tatsuhito , Takata Toshikazu
Published: December 2020

Incorporation of rotaxane scaffolds into the crosslinking points of polymer networks significantly affects their rheological and mechanical properties. The present study involves the synthesis of a new rotaxane‐type crosslinker containing nitrile N‐oxide functional groups on both the axle and wheel components. The prepared crosslinker is highly reactive; however, it can be isolated and applied in the crosslinking reaction of a commercially important polymer, namely ethylene‐propylene‐butadiene monomer rubber (EPDM), in the absence of additives and catalysts. Tensile tests reveal that compared to a network containing conventional crosslinking points, both breaking strength and strain of the network structure prepared herein are improved due to the incorporation of movable crosslinking points. The synthesized network structure also exhibits five times higher fracture energy. The developed post‐crosslinking methodology for the direct introduction of movable crosslinking points into pre‐formed polymers will be valuable in the production of rotaxane materials for various applications.
Burned out or engaged at work? The role of self‐regulatory personality profiles
Authors: Smith Claire E. , Barratt Clare L. , Hirvo Alexis
Published: December 2020

Employees’ responses to work demands are crucially related to their occupational well‐being. The present study aimed to identify Big Five personality profiles of working adults and examine their connection to two central responses to work stress: work engagement and burnout. Four latent personality profiles emerged (i.e., overcontroller, undercontroller, reserved and resilient) and, in line with Block (2002) self‐regulation theory, related differently to burnout and engagement. Specifically, both under‐ and overcontrollers experienced higher burnout and lower engagement, whereas resilient experienced higher engagement and lower burnout. Reserved profile members were low in both. The results suggest that management of healthy, engaged workers may be aided by consideration of personality profiles and that Block's self‐regulation theory may be a useful framework for connecting personality to occupational well‐being.
Changes in the phonon density of states of Fe induced by external strain
Authors: Meyer Robert , Scherthan Lena , Hochdörffer Tim , Sadashivaiah Sakshath , Wolny Juliusz A. , Klein Matthias W. , Smaga Marek , Beck Tilmann , Schünemann Volker , Urbassek Herbert M.
Published: December 2020

Nuclear inelastic scattering of synchrotron radiation is used to study the changes induced by external tensile strain on the phonon density of states (pDOS) of polycrystalline Fe samples. The data are interpreted with the help of dedicated atomistic simulations. The longitudinal phonon peak at around 37 meV and also the second transverse peak at 27 meV are decreased under strain. This is caused by the production of defects under strain. Also the thermodynamic properties of the pDOS demonstrate a weakening of the force constants and of the mean phonon energy under strain. Remaining differences between experiment and simulation are discussed.
Impact of frailty on periprocedural health care utilization in patients undergoing transcatheter edge-to-edge mitral valve repair
Authors: Iliadis Christos , Schwabe Leandra , Müller Dirk , Stock Stephanie , Baldus Stephan , Pfister Roman
Published: December 2020

Background

Frailty is a common characteristic of patients undergoing transcatheter mitral valve repair (TMVR). It is unclear whether the physical vulnerability of frail patients translates into increased procedural health care utilization.

Methods and results

Frailty was assessed using the Fried criteria in 229 patients undergoing TMVR using the MitraClip system at our institution and associations with total costs and costs by cost centers within the hospital incurred during periprocedural hospitalization were examined. Frail patients (n = 107, 47%) compared to non-frail patients showed significantly higher total costs [median/interquartile range, excluding implant costs: 7,337 € (5,911–9,814) vs 6,238 € (5,584–7,499), p = 0.001], with a difference in means of 2,317 €. Frailty was the only clinical baseline characteristic with significant association with total costs. Higher total costs in frail patients were attributable primarily to longer stay on intermediate/intensive care unit (3.8 ± 5.7 days in frail vs 2.1 ± 1.7 days in non-frail, p = 0.003), but also to costs of clinical chemistry and physiotherapy. The prolonged stay on intermediate/intensive care unit in frail patients was attributable to postprocedural complications such as bleeding, kidney injury, infections and cardiovascular instability.

Conclusion

Frailty is associated with a mean 32% increase of hospital costs in patients undergoing TMVR, which is primarily the result of a prolonged recovery and increased vulnerability to complications. These findings are valuable for a hospital’s total cost calculation and resource allocation planning. Since frailty is regarded a potentially reversible health state, preventive interventions may help reduce costs in frail patients.

Graphic abstract
Transferability of N-terminal mutations of pyrrolysyl-tRNA synthetase in one species to that in another species on unnatural amino acid incorporation efficiency
Authors: Williams Thomas L. , Iskandar Debra J. , Nödling Alexander R. , Tan Yurong , Luk Louis Y. P. , Tsai Yu-Hsuan
Published: December 2020

Genetic code expansion is a powerful technique for site-specific incorporation of an unnatural amino acid into a protein of interest. This technique relies on an orthogonal aminoacyl-tRNA synthetase/tRNA pair and has enabled incorporation of over 100 different unnatural amino acids into ribosomally synthesized proteins in cells. Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA from Methanosarcina species are arguably the most widely used orthogonal pair. Here, we investigated whether beneficial effect in unnatural amino acid incorporation caused by N-terminal mutations in PylRS of one species is transferable to PylRS of another species. It was shown that conserved mutations on the N-terminal domain of MmPylRS improved the unnatural amino acid incorporation efficiency up to five folds. As MbPylRS shares high sequence identity to MmPylRS, and the two homologs are often used interchangeably, we examined incorporation of five unnatural amino acids by four MbPylRS variants at two temperatures. Our results indicate that the beneficial N-terminal mutations in MmPylRS did not improve unnatural amino acid incorporation efficiency by MbPylRS. Knowledge from this work contributes to our understanding of PylRS homologs which are needed to improve the technique of genetic code expansion in the future.
Oral contraceptive use by formulation and endometrial cancer risk among women born in 1947–1964: The Nurses’ Health Study II, a prospective cohort study
Authors: Burchardt Norah A. , Shafrir Amy L. , Kaaks Rudolf , Tworoger Shelley S. , Fortner Renée T.
Published: December 2020

Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with longer-term risk. A total of 107,069 women from the Nurses’ Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 [95% CI 0.65–0.91]; >10 years of use, 0.43 [0.32–0.58] vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (> 5 years) of ethinyl estradiol (0.52 [0.41–0.67]) and second-generation progestins (0.43 [0.30–0.61]), both versus never use, were more strongly associated with lower risk than mestranol (0.66 [0.50–0.88], p-het = 0.01) and first-generation progestins (0.62 [0.49–0.78], p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (< vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations.
DSC examination of cartilage damage of patients undergoing shoulder replacement
Authors: Bata András , Nöt László G. , Szabó Hajnalka , Cifra János , Lőrinczy Dénes
Published: December 2020

Shoulder replacement is a viable surgical treatment for comminuted proximal humerus fractures and shoulder osteoarthritis. Proper evaluation of hyaline cartilage is essential for the right choice of prosthesis; however, there are only a limited number of studies available investigating the cartilage of glenohumeral joint of patients undergoing shoulder replacement. We hypothesized that differential scanning calorimetry (DSC) could determine the grade of cartilage damage in patients undergoing reversed shoulder replacement, providing insights into the structural changes of the human cartilage samples. Sample of hyaline cartilage of glenohumeral joint was harvested during reversed shoulder replacement of orthopaedic and trauma patients. Thermal parameters were measured using DSC, and radiological examination of glenohumeral joint was also done prior to surgery. We have found that changes in thermal characteristics and DSC scans clearly indicate the severity of osteoarthritis and cartilage damage. The denaturation temperature range and the half-width of the heat flow curves were significantly wider in the orthopaedic samples compared to the control and traumatic ones. The calorimetric enthalpy (ΔHcal) exhibited significant differences in both pathologic samples, compared to the control. The melting temperatures (Tm) show that structural change caused by orthopaedic condition is greater than the effect of traumatic. Therefore, differential scanning calorimetry could help to determine the grade of cartilage damage in orthopaedic and trauma patients undergoing reversed shoulder replacement.