bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dual‐Targeting Circular Aptamer Strategy Enables the Recognition of Different Leukemia Cells with Enhanced Binding Ability
Authors: Ai Lili , Peng Tianhuan , Li Yingying , Kuai Hailan , Sima Yingyu , Su Minhui , Wang Dan , Yang Qiuxia , Wang Xue‐Qiang , Tan Weihong
Published: October 2021

Currently, the broad use of monovalent aptamers in oncology faces challenges, including insufficient recognition and internalization caused by a finite number of receptors on the cell surface, as well as a confined recognition spectrum. Herein, we describe the development of a dual‐targeting circular aptamer (DTCA) that can recognize two different biomarkers on living cells to augment aptamer–receptor interactions, thus enhancing recognition of the target cells. This improvement not only boosts binding and internalization abilities, but also expands the recognition spectrum of these aptamers to different leukemia cells. Moreover, the stability of DTCA in serum can be significantly improved by an enzyme‐promoted terminal ligation strategy. The chemical incorporation of 5‐fluorodeoxyuridine into DTCA resulted in a pharmaceutically functional aptamer that exhibited excellent selectivity, as demonstrated by its high cytotoxicity against target cancer cells, but not to normal cells. The superiority of our newly developed strategy was further highlighted by its precise tumor‐imaging capability.
Macrocycle Dynamics in a Branched [8]Catenane Controlled by Three Different Stimuli in Three Different Regions
Authors: Ng Antony Wing Hung , Lai Samuel Kin‐Man , Yee Chi‐Chung , Au‐Yeung Ho Yu
Published: October 2021

A branched [8]catenane from an efficient one‐pot synthesis (72 % HPLC yield, 59 % isolated yield) featuring the simultaneous use of three kinds of templates and cucurbit[6]uril‐mediated azide–alkyne cycloaddition (CBAAC) for ring‐closing is reported. Design and assembly of the [8]catenane precursors are unexpectedly complex that can involve cooperating, competing and non‐influencing interactions. Due to the branched structure, dynamics of the [8]catenane can be modulated in different extent by rigidifying/loosening the mechanical bonds at different regions by using solvent polarity, acid‐base and metal ions as the stimuli. This work not only highlights the importance of understanding the delicate interplay of the weak and non‐obvious supramolecular interactions in the synthesis of high‐order [n]catenane, but also demonstrates a complex control of dynamics and flexibility for exploiting [n]catenanes applications.
Chiroptical Switching and Quantitative Chirality Sensing with (Pseudo)halogenated Quinones
Authors: Formen Jeffrey S. S. K. , Wolf Christian
Published: October 2021

(Pseudo)halogenated quinones react smoothly with chiral amines, amino alcohols, and amino acids toward push–pull conjugates with optical sensing and switching applications. The chiroptically active conjugates serve as redox switches between two reversibly interconverting states with remarkably different UV and CD signatures. Addition of sodium borohydride generates a hydroquinone derivative that is quantitatively re‐oxidized to the original quinone upon exposure to air. This chiroptical quinone/hydroquinone redox switch system combines several attractive features such as simple set‐up, use of inexpensive chemicals, short response time, and thermal and photochemical stability. A conceptually new sensing approach that is based on integrated chiroptical amplification and redox switching enables on‐the‐fly deconvolution of otherwise overlapping CD spectra and is used for quantitative er analysis of challenging samples containing constitutional isomers in varying enantiomeric compositions.
Tetraaryldiborane(4) Can Emit Dual Fluorescence Responding to the Structural Change around the B–B Bond
Authors: Shoji Yoshiaki , Tanaka Naoki , Ikabata Yasuhiro , Sakai Hayato , Hasobe Taku , Koch Norbert , Nakai Hiromi , Fukushima Takanori
Published: October 2021

We report the successful synthesis of tetramesityldiborane(4) (Mes4B2) through the reductive coupling of a dimesitylborinium ion. Owing to the steric protection conferred by the mesityl groups, Mes4B2 shows exceptional chemical stability and remains intact in water. Single‐crystal X‐ray analysis revealed that Mes4B2 has an orthogonal geometry, where the B–B center is completely hidden by the mesityl groups. Remarkably, Mes4B2 emits dual fluorescence at 460 and 620 nm, both in solution and in the solid state. Theoretical calculations showed that Mes4B2 in the excited S1 state adopts a twisted or planar geometry, which is responsible for the shorter‐ or longer‐wavelength fluorescence, respectively. The intensity ratio of the dual fluorescence is sensitive to the viscosity of the medium, which suggests that Mes4B2 has potential as a ratiometric viscosity sensor.
Facile method towards mono‐component polyurea composite coating with excellent mechanical properties and self‐recovery ability
Authors: Zhu Yiqiao , Wen Jie , Wang Lin , Yi Longfei , Song Dayu
Published: October 2021

Polymeric coatings are often suffered from damages or irreversible deformations due to external impact during their server life, which may have adverse influences on the protection effect and aesthetics. Developing coatings that are mechanically robust and capable of recovering from deformation is urgently needed yet highly challenging. In this work, a class of mono‐component polyurea/asphalt composite coatings with excellent mechanical properties and self‐recovery ability is prepared through a facile method. The FTIR measurements indicate that the asphalt can react with polyurea, thus the interaction between asphalt and polyurea is enhanced. As a result, the mechanical stress and toughness of polyurea are increased. Moreover, the hydrogen bonds in the composite are identified by variable‐temperature FTIR, which endows the composite coating with self‐recovery ability as revealed by cyclic tensile tests. In addition, the thermal stability of polyurea is also improved after the inclusion of asphalt. Except for mechanically reinforcing, the incorporation of asphalt can also cut the cost as the mechanical properties of the composite coating are still better than pure polyurea even with 20 wt% asphalt. Moreover, the preparing process of the composite coating are quite facile, which hold great promise for large‐scale production and application.
Synthesis and characterization of phenylated phenylenediamine and bisphenol a diglycidyl ether epoxy networks
Authors: Budy Stephen M. , Wey Anderson , Wu Angelina , Son David Y.
Published: October 2021

A new highly aromatic hardener, phenylated phenylenediamine (PDA), was synthesized utilizing a Diels‐Alder reaction to afford a mixture of para and meta conformations. This new hardener was cured with bisphenol A diglycidyl ether (BADGE). To investigate the conformational mixture, pure 1,4‐benzenediamine and 1,3‐benzenediamine were cured with BADGE. DSC was employed to observe cure curves affording the onset (73, 74, and 146°C for 1,4‐benzenediamine, 1,3‐benzenediamaine, and phenylated phenylenediamine, respectively), peak (128, 151, and 206°C, respectively), and enthalpy change (385, 526, and 238 J/g, respectively), as well as the glass transition temperature (103, 151, and 212°C, respectively). ATR‐FTIR spectroscopy provided information on the structures of the cured network samples, including loss of oxirane and primary amine vibrations after curing. TGA and DMA were used to determine thermal stability (Td,N2 = 332, 367, and 380°C, respectively) and thermal mechanical properties including storage (E′ = 200, 150, and 350 MPa, respectively), loss modulus (E″ = 10, 10, and 40 MPa, respectively), and tan delta (102, 180, and 209°C, respectively).
New discussion about the approximate controllability of fractional stochastic differential inclusions with order 1 < r < 2
Authors: Dineshkumar C. , Nisar Kottakkaran Sooppy , Udhayakumar R. , Vijayakumar V.
Published: October 2021

In this manuscript, our main focus is about the approximate controllability of fractional stochastic differential inclusions with order 1 < r < 2. With the utilization of the fractional calculations, the findings and facts associated with multivalued maps, the fixed‐point method, and the principal discussions are demonstrated. First, we focus on the approximate controllability of our system. Lastly, we provide an application for the demonstration of theoretical results.
Design aspects of COVID‐19 treatment trials: Improving probability and time of favorable events
Authors: Beyersmann Jan , Friede Tim , Schmoor Claudia
Published: October 2021

As a reaction to the pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a multitude of clinical trials for the treatment of SARS‐CoV‐2 or the resulting corona disease 2019 (COVID‐19) are globally at various stages from planning to completion. Although some attempts were made to standardize study designs, this was hindered by the ferocity of the pandemic and the need to set up clinical trials quickly. We take the view that a successful treatment of COVID‐19 patients (i) increases the probability of a recovery or improvement within a certain time interval, say 28 days; (ii) aims to expedite favorable events within this time frame; and (iii) does not increase mortality over this time period. On this background, we discuss the choice of endpoint and its analysis. Furthermore, we consider consequences of this choice for other design aspects including sample size and power and provide some guidance on the application of adaptive designs in this particular context.
Average user ratings prompt disparate decision strategies in online retail shopping
Authors: LaCour Mark , Serra Michael J.
Published: October 2021

Online shoppers have a vast array of information available to aid their purchasing decisions (e.g., average user ratings, histograms of ratings). Past research is ambiguous regarding the degree to which shoppers try to simplify this information integration process. Some results suggest that customers will invest a substantial amount of time and effort into the decision process, while others suggest that customers prefer to keep the process as simple as possible and avoid extra effort. In the present study, we sought to examine the conditions under which people will use heuristic strategies versus more analytic ones. We found that the average user rating plays a large role in determining which strategy customers use to integrate product information into a purchasing decision. We show that people use a “binary bias”—assessing the relative number of “high” and “low” ratings and choosing items with the more favorable ratio—when products have a lackluster (~three‐star) average user rating. However, when average ratings are higher, customers instead use even simpler cues to make decisions. We also found evidence that individual differences in analytical thinking dispositions are associated with using more effortful information integration strategies. Thus, the present research suggests different strategies for displaying product information to customers depending on the average user ratings of the product and characteristics of the shoppers themselves.
A Bioorthogonal‐Activated Fluorescence Turn‐On Probe Based on Nitrone‐Modified 1,8‐Naphthalimide for Live‐Cell Imaging
Authors: Teng Yu , Yang Hong , Li Xiang , Wang Yongcheng , Yin Dali , Tian Yulin
Published: October 2021

Comprehensive Summary

A nitrone‐modified 1,8‐naphthalimide was designed as a novel bioorthogonal‐activated turn‐on probe based on strain‐promoted alkyne‐nitrone cycloaddition (SPANC). The bioorthogonal cycloadducts were subsequently transformed into fluorescent rearrangement products by photo‐acceleration, which exhibited significant fluorescence enhancement, large stokes shift, and high fluorescence quantum yield. DFT calculations were performed to elucidate the fluorescence OFF‐ON mechanism. This fluorogenic strategy was successfully applied to labeling of proteins and visualizing mitochondria in live cells in real time.
Self‐help smoking cessation intervention for Spanish‐speaking Hispanics/Latinxs in the United States: A randomized controlled trial
Authors: Simmons Vani N. , Sutton Steven K. , Medina‐Ramirez Patricia , Martinez Ursula , Brandon Karen O. , Byrne Margaret M. , Meade Cathy D. , Meltzer Lauren R. , Brandon Thomas H.
Published: October 2021

Background

Hispanic/Latinx smokers living in the United States face unique challenges in quitting smoking. This study evaluated the efficacy of a culturally relevant, Spanish‐language, extended self‐help smoking cessation intervention among Hispanic smokers.

Methods

A 2‐arm parallel randomized controlled trial was conducted with Hispanic/Latinx smokers living in the United States who preferred health information in Spanish and smoked 5 or more cigarettes per week. Participants were randomly allocated to receive Libre del Cigarrillo (LDC), which consisted of 11 booklets and 9 pamphlets mailed monthly over 18 months, or the usual care (UC), which was a single Spanish‐language self‐help booklet from the National Cancer Institute. The primary outcome was self‐reported 7‐day point prevalence smoking abstinence assessed 6, 12, 18, and 24 months after the baseline. Eight prespecified moderators of the intervention were evaluated. Cost‐effectiveness was also evaluated. All statistical tests were 2‐sided.

Results

Data from all participants randomized to LDC (n = 714) or UC (n = 703) were used for analyses after multiple imputation to manage missing data. Generalized estimating equation analyses indicated that LDC abstinence rates were higher (P < .001) across all assessments. Logistic regression analyses revealed that at 24 months, the abstinence rate was greater for LDC (33.1%) than UC (24.3%; odds ratio, 1.54; 95% confidence interval, 1.18‐2.02; P = .002). Men exhibited a strong intervention effect at all assessments (P values < .001), whereas the intervention effect for women was observed only at 6 and 12 months (P values < .018). In comparison with UC, the incremental cost per quitter in the LDC arm was $648.43 at 18 months and $683.93 at 24 months.

Conclusions

A culturally relevant, Spanish‐language intervention was efficacious and cost‐effective for smoking cessation.

Lay Summary

Research is needed to develop interventions for ethnic minority smokers.

The aim of the current study was to test a Spanish‐language adaptation of a validated and easily implemented self‐help smoking cessation intervention in a nationwide randomized controlled trial.

The findings demonstrated that the intervention produced greater smoking abstinence in comparison with a standard self‐help booklet.

Participants also were more satisfied with the intervention, and it was cost‐effective.

Efforts aimed at promoting tobacco abstinence in this underserved population could have significant public health implications, including potential reductions in cancer health disparities associated with tobacco smoking.
The effectiveness of the information‐motivation model and domestic brushing with a hypochlorite‐based formula on peri‐implant mucositis: A randomized clinical study
Authors: Cosola Saverio , Oldoini Giacomo , Giammarinaro Enrica , Covani Ugo , Genovesi Annamaria , Marconcini Simone
Published: October 2021

Objective

Management of mucositis is essential for the long‐term maintenance of dental implants. This study determined the efficacy, in terms of clinical parameters, of an adjunctive domiciliary agent paired with non‐surgical periodontal therapy (NSPT) for patients with peri‐implant mucositis.

Materials and methods

Patients involved in a periodontal maintenance program were randomly distributed to the domestic use of a chlorhexidine toothpaste and mouthwash (control) or a hypochlorite‐based formula brushing solution (test) after diagnosis of peri‐implant mucositis. A modified approach towards NSPTwas performed after 10 days of domestic use of the assigned maintenance product in both groups. Clinical and patient‐related outcomes were recorded during a 90‐day follow‐up period.

Results

Forty patients completed the three‐month study (20 patients per group). Both groups showed relevant clinical and patient outcome improvements after the NSPT (T2) and between T1 and T2 (p < 0 0.01), except for PPD. For the test group, the clinical improvement was significantly greater than that for the control group at the seventh‐day evaluation (T1) in the gingival index (0–3) and FMBS (%). Favorable outcomes were maintained during the entire follow‐up period.

Conclusion

The present study showed that the modified NSPT paired with the domestic use of nitradine‐based formula helps resolve peri‐implant mucositis and that nitradine might represent an alternative to chlorhexidine in these cases.

Clinical relevance

The gold standard for nonsurgical maintenance is full‐mouth disinfection. A previous decontamination of the oral cavity with chlorhexidine or nitradine domiciliary for 10 days could reduce plaque and inflammation, resulting in a painless operative session. This protocol may help reduce airborne contamination and the risk of cross‐infection, and during the pandemic, the protocol is safer for clinicians. In the same clinical cases, nitradine may be more efficient than chlorhexidine, and the former has no side effects such as discolouration.
Revisiting the effect of PCR replication and sequencing depth on biodiversity metrics in environmental DNA metabarcoding
Authors: Shirazi Sabrina , Meyer Rachel S. , Shapiro Beth
Published: October 2021

Environmental DNA (eDNA) metabarcoding is an increasingly popular tool for measuring and cataloguing biodiversity. Because the environments and substrates in which DNA is preserved differ considerably, eDNA research often requires bespoke approaches to generating eDNA data. Here, we explore how two experimental choices in eDNA study design—the number of PCR replicates and the depth of sequencing of PCR replicates—influence the composition and consistency of taxa recovered from eDNA extracts. We perform 24 PCR replicates from each of six soil samples using two of the most common metabarcodes for Fungi and Viridiplantae (ITS1 and ITS2), and sequence each replicate to an average depth of ~84,000 reads. We find that PCR replicates are broadly consistent in composition and relative abundance of dominant taxa, but that low abundance taxa are often unique to one or a few PCR replicates. Taxa observed in one out of 24 PCR replicates make up 21–29% of the total taxa detected. We also observe that sequencing depth or rarefaction influences alpha diversity and beta diversity estimates. Read sampling depth influences local contribution to beta diversity, placement in ordinations, and beta dispersion in ordinations. Our results suggest that, because common taxa drive some alpha diversity estimates, few PCR replicates and low read sampling depths may be sufficient for many biological applications of eDNA metabarcoding. However, because rare taxa are recovered stochastically, eDNA metabarcoding may never fully recover the true amplifiable alpha diversity in an eDNA extract. Rare taxa drive PCR replicate outliers of alpha and beta diversity and lead to dispersion differences at different read sampling depths. We conclude that researchers should consider the complexity and unevenness of a community when choosing analytical approaches, read sampling depths, and filtering thresholds to arrive at stable estimates.
Stemflow infiltration areas into forest soils around American beech (Fagus grandifolia Ehrh.) trees
Authors: Llorens Pilar , Latron Jérôme , Carlyle‐Moses Darryl E. , Näthe Kerstin , Chang Jeffrey L. , Nanko Kazuki , Iida Shin'ichi , Levia Delphis F.
Published: October 2021

The size of stemflow infiltration areas around the boles of trees is currently a topic of interest and debate within the hydrologic community. There is a gap in our knowledge of stemflow infiltration areas in many wooded ecosystems and a need for more than the few studies that have examined stemflow infiltration areas directly. Hence, this field study was specifically undertaken to mitigate the existing data gap by providing direct measurements of stemflow infiltration areas from high stemflow‐producing American beech (Fagus grandifolia Ehrh.) trees. Different stemflow rates (290, 72 and 31 L h−1) were simulated using dye‐infused stemflow and the areas of stemflow infiltration around four trees determined by measuring the areal extent of dye on the soil surface. Our results revealed that stemflow infiltration areas ranged from 0.0035 to 0.0951 m2 tree−1. The mean basal area funnelling ratio was 46.5 ± 1.8, whereas the funnelling ratios per unit infiltration areas,
, were between 32.0 and 258.4. Despite intentionally high stemflow rates, chosen to compensate for the high infiltration capacities of forest soils, these results reinforce the fact that stemflow is an extremely localized input in natural forests. Thus, these results, even if specific to F. grandifolia within a particular forest and soil type, support a growing body of work indicating that stemflow infiltration areas are usually <1 m2, and often much smaller, in natural forests. Moreover, the high values of
provide further evidence indicating that stemflow inputs are important for the development of hot spots in near‐trunk soils.
Marine restoration governance arrangements: Issues of legitimacy
Authors: Ramírez‐Monsalve Paulina , Coelho Nelson F. , Carballo‐Cárdenas Eira , van Tatenhove Jan P. M. , Papadopoulou Nadia , Smith Chris J.
Published: October 2021

A new motivation for marine restoration has been observed, associated with the dissatisfaction with current marine restoration governance arrangements (MRGAs). An MRGA consists of alliances of public and private actors (coalitions) who, through their common conceptualisation of the problem (discourses), try to influence and design marine restoration activities while considering the rules of decision‐making, and the management of limited resources. Emerging MRGAs rise in parallel to existing ones and aim to contribute to the same goals or show another way of reaching those goals. This phenomenon raises questions of legitimacy both for the emerging and the existing arrangement. Building on existing literature, this paper proposes an analytical framework to simultaneously explore input, throughput and output legitimacy as three essential pre‐conditions of legitimacy for MRGAs. The framework is tested in three European cases of MRGAs that were part of the European Union MERCES project (http://www.merces-project.eu/). Analysis showed that actors who are influential in achieving restoration goals, and also those who are impacted by restoration actions, should be involved in the MRGAs (input legitimacy); actors within MRGAs should establish and follow procedures for decision‐making that are both transparent and clear (throughput legitimacy); and actors within MRGAs need to establish a common understanding of restoration, of the goal to reach and of the related uncertainties (output legitimacy). Awareness of these pre‐conditions allows actors internal and external to MRGAs to address aspects that give legitimacy to restoration actions. It also creates a language that allows actors to engage in discussion on legitimacy that goes beyond the mere application of the rule of law.
Synthesis of Novel Pseudocloso Ruthenacarboranes based on an Unsubstituted nido‐C2B9H112− Ligand
Authors: Kaltenberg Alexander A. , Somov Nikolay V. , Malysheva Yulia B. , Vorozhtsov Dmitry L. , Grishin Ivan D.
Published: October 2021

The reaction of the known closo‐ruthenacarborane 3‐H‐3‐Cl‐3,3‐(PPh3)2‐closo‐3,1,2‐RuC2B9H11 with tridentade nitrogen‐based ligands of the general formula (C5NH4CH2)2NR (R=H, Me, Et, iPr, But) in benzene solution at 60 °C allowed us to isolate novel ruthenacarborane clusters 3,3,3‐(2’‐NC5H4CH2)2NR‐pseudocloso‐3,1,2‐RuC2B9H11. According to the performed X‐ray study, the obtained compounds are the first examples of pseudocloso‐metallacarboranes bearing unsubstituted C2B92− nido‐carborane ligand. In spite of the determined pseudocloso structure of the complexes in the solid state, the recorded 11B{1H} NMR spectra indicate that some of them are converted into the closo isomers in solution. The conducted quantum‐chemical calculations have confirmed the subtle difference between two configurations and possible rearrangement in solution. The performed electrochemical investigations show the ability of the formed ruthenacarboranes to undergo reversible oxidation to Ru(III) species.
Co(II) Amide, Pyrrolate, and Aminopyridinate Complexes: Assessment of their Manifold Structural Chemistry and Thermal Properties**
Authors: Zanders David , Boysen Nils , Land Michael A. , Obenlüneschloß Jorit , Masuda Jason D. , Mallick Bert , Barry Seán T. , Devi Anjana
Published: October 2021

A series of cobalt(II) (silyl)amides, pyrrolates and aminopyridinates were synthesized. Inspired by the dimeric bis(trimethylsilylamido)cobalt(II) complex ([Co(TMSA)2]2), facile salt metathesis employing the ligand 2,2,5,5‐tetramethyl‐1,2,5‐azadisilolidinyl (TMADS) yielded its congener [Co(TMADS)2]2. Novel, heteroleptic Lewis adducts of the former resulted in unusual three‐ to four‐fold coordination geometry around the metal center. Similarily, the salt [Li(DAD)2][Co(TMADS)3] was isolated which demonstrates an ion separated Co(II) anion with silylamide ligation and Li+ counter cation. Transpyrrolylation using [Co(TMSA)2]2 was established for the synthesis of bis[N,N’‐2‐(dimethylaminomethyl)pyrrolyl]cobalt(II), and bis(N‐2‐(tert‐butyliminomethyl)pyrrolyl)cobalt(II). Treatment of CoCl2 with two equivalents of lithiated N,N‐dimethyl(N’‐tert‐butyl)ethane‐1‐amino‐2‐amide and N,N‐dimethyl(N’‐trimethylsilyl)ethane‐1‐amino‐2‐amide resulted in the respective Co(II) amido‐amines. Reaction of CoCl2 with lithium 4‐methyl‐N‐(trimethylsilyl)pyridine‐2‐amide yielded the first binuclear, homoleptic Co(II) aminopyridinate complex with a distorted trigonal bipyramidal coordination environment (τ5=0.533) for one central Co(II) ion and a weakly distorted tetrahedral coordination geometry (τ4=0.845) for the other. All of the new compounds were thoroughly characterized in terms of composition and structure. Finally, the key thermal characteristics of volatility and thermal stability were assessed using a combination of thermogravimetric analysis and complementary bulk sublimation experiments.
From Enantioenriched Donor‐Acceptor Cyclopropylcarbinols to Axially Chiral Arylnaphthalenes through Aryldihydronaphthalenes: Central‐to‐Axial Chirality Exchange
Authors: Saito Taichi , Shimizu Yuka , Araki Yusuke , Ohgami Yoshino , Kitazawa Yu , Nishii Yoshinori
Published: October 2021

Transformations of enantioenriched donor‐acceptor (D−A) cyclopropylcarbinols to enantioenriched 1‐arylnaphthalenes that bear anortho‐substituent on a benzene ring provided a successful chirality‐exchange method with a high level of stereoinduction. A central chirality‐transfer step, i. e., a Lewis‐acid‐mediated ring‐opening cyclization of enantioenriched D‐A cyclopropylcarbinols (97 to >99 % ee), afforded 1‐aryl‐1,2‐dihydronaphthalenes with anortho‐substituent (Me, Br, OMe, OBn, or OiPr) on the benzene ring with high enantioselectivity (97 to >99 % ee). The central‐to‐axial chirality‐exchange step, i. e., the dehydrogenation of the obtained enantioenriched 1‐aryl‐1,2‐dihydronaphthalenes using DDQ, furnished the axially chiral 1‐arylnaphthalenes with high enantioselectivity (90 to >99 % ee). Importantly, we developed a highly enantioselective synthesis of a 1‐arylnaphthalene with anortho‐alkoxy group on the benzene ring. Moreover, we improved the chirality exchange to furnish a 1‐arylnaphthalene with anortho‐alkoxy‐substituted benzene ring in high yield with high ee.
Liver Disease and Risk of Hepatocellular Carcinoma in Children With Mutations in TALDO1
Authors: Grammatikopoulos Tassos , Hadzic Nedim , Foskett Pierre , Strautnieks Sandra , Samyn Marianne , Vara Roshni , Dhawan Anil , Hertecant Jozef , Al Jasmi Fatma , Rahman Obydur ,   University of Washington Center for Mendelian Genomics, Deheragoda Maesha , Bull Laura N. , Thompson Richard J
Published: October 2021

Mutations in the transaldolase 1 (TALDO1) gene have been described in a limited number of cases. Several organs can be affected and clinical manifestations are variable, but often include liver dysfunction and/or hepatosplenomegaly. We report 4 patients presenting with liver disease: 2 with early‐onset hepatocellular carcinoma (HCC). Patients with cholestasis and mutations in TALDO1 were identified by next‐generation sequencing. Clinical, laboratory, and histological data were collected. Four (1 male) patients were identified with variants predicted to be damaging in TALDO1. Three patients were homozygous (two protein truncating/one missense mutations), 1 one was compound heterozygous (two missense mutations). Median age at presentation was 4 months (range, 2‐210 days) with jaundice (3), hepatosplenomegaly (3), and pancytopaenia (1). The diagnosis was corroborated by detection of minimal transaldolase enzyme activity in skin fibroblasts in two cases and raised urine polyols in the third. Three patients underwent liver transplantation (LT), 2 of whom had confirmed HCC on explanted liver. One patient suddenly died shortly after LT. The nontransplanted case has a chronic liver disease with multiple dysplastic liver nodules, but normal liver biochemistry and alpha‐fetoprotein. Median follow‐up was 4 years (range, 1‐21). Conclusion: Transaldolase deficiency can include early‐onset normal gamma‐glutamyltransferase liver disease with multisystem involvement and variable progression. Patients with this disease are at risk of early‐onset HCC and may require early LT.
Low Lipoprotein(a) Levels Predict Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease
Authors: Meroni Marica , Longo Miriam , Lombardi Rosa , Paolini Erika , Macchi Chiara , Corsini Alberto , Sirtori Cesare R. , Fracanzani Anna Ludovica , Ruscica Massimiliano , Dongiovanni Paola
Published: October 2021

Dyslipidemia and cardiovascular complications are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis up to hepatocellular carcinoma. Lipoprotein(a) (Lp(a)) has been associated with cardiovascular risk and metabolic abnormalities, but its impact on the severity of liver damage in patients with NAFLD remains to be clarified. Circulating Lp(a) levels were assessed in 600 patients with biopsy‐proven NAFLD. The association of Lp(a) with liver damage was explored by categorizing serum Lp(a) into quartiles. The receiver operating characteristic curve was used to analyze the accuracy of serum Lp(a) in hepatic fibrosis prediction. Hepatic expression of lipoprotein A (LPA) and of genes involved in lipid metabolism and fibrogenic processes were evaluated by RNA sequencing in a subset of patients with NAFLD for whom Lp(a) dosage was available (n = 183). In patients with NAFLD, elevated Lp(a) levels were modestly associated with circulating lipids, carotid plaques, and hypertension (P < 0.05). Conversely, patients with low serum Lp(a) displayed insulin resistance (P < 0.05), transaminase elevation (P < 0.05), and increased risk of developing severe fibrosis (P = 0.007) and cirrhosis (P = 0.002). In addition, the diagnostic accuracy of Lp(a) in predicting fibrosis increased by combining it with transaminases (area under the curve fibrosis stage 4, 0.87; P < 0.0001). Hepatic LPA expression reflected serum Lp(a) levels (P = 0.018), and both were reduced with the progression of NAFLD (P < 0.05). Hepatic LPA messenger RNA levels correlated with those of genes involved in lipoprotein release, lipid synthesis, and fibrogenesis (P < 0.05). Finally, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, apolipoprotein E (ApoE) rs445925, and proprotein convertase subtilisin/kexin type 9 (PCSK9) rs7552841, known variants that modulate circulating lipids, may influence serum Lp(a) levels (P < 0.05). Conclusion: Circulating Lp(a) combined with transaminases may represent a novel noninvasive biomarker to predict advanced fibrosis in patients with NAFLD.
LINC00152 expression in normal and Chronic Lymphocytic Leukemia B cells
Authors: Matis Serena , Rossi Martina , Brondolo Lorenzo , Cardillo Martina , Reverberi Daniele , Massara Rosanna , Colombo Monica , Ibatici Adalberto , Angelucci Emanuele , Vaisitti Tiziana , Bruno Silvia , Fabris Sonia , Neri Antonino , Gentile Massimo , Morabito Fortunato , Cutrona Giovanna , Briata Paola , Gherzi Roberto , Fais Franco
Published: October 2021

Long non‐coding RNAs are emerging as essential regulators of gene expression, but their role in normal and neoplastic B cells is still largely uncharacterized. Here, we report on the expression pattern of the LINC00152 in normal B cells and Chronic Lymphocytic Leukemia B cell clones. Higher LINC00152 levels were consistently observed in memory B cell populations when compared to naïve B cells in the normal tissues analyzed [peripheral blood (PB), tonsils, and spleen]. In addition, independent stimulation via Immunoglobulins (IG), CD40, or Toll‐like Receptor 9 (TLR9) upregulated LINC00152 in PB B cells. The expression of LINC00152 in a cohort of 107 early stage Binet A CLL patients was highly variable and did not correlate with known prognostic markers or clinical evolution. TLR9 stimulation, but not CD40 or IG challenge, was able to upregulate LINC00152 expression in CLL cells. In addition, LINC00152 silencing in CLL cell lines expressing LINC00152 failed to induce significant cell survival or apoptosis changes. These data suggest that, in normal B cells, the expression of LINC00152 is regulated by immunomodulatory signals, which are only partially effective in CLL cells. However, LINC00152 does not appear to contribute to CLL cell expansion and/or survival in a cohort of newly diagnosed CLL patients.
Frequency of and risk factors for intensive care unit‐acquired sacrum pressure injuries in critically ill patients: A multicenter cross‐sectional study in China
Authors: Hu Binqin , Zhao Yang , Yang Jijun , Zeng Zhenhua , Wu Yanhong , Gui Chunmei , Gong Jiang , Gao Yi , Yang Yong , Luo Cuizhu , Wang Yu , Jiang Qingjuan , Guo Wenlong , Lu Pan , Yuan Fen , Li Xiaofang , Dai Xingui
Published: October 2021

Rationale, aims, and objectives

Hospital‐acquired pressure injuries (HAPI) prolong hospital stays and are an important health problem worldwide. The aim of this study was to assess the frequency of and risk factors for intensive care unit (ICU)‐acquired pressure injuries (IAPI) on the sacrum in critically ill patients in China.

Methods

We performed a multicenter, cross‐sectional survey of IAPI on the sacrum in 23 adult ICUs in 19 hospitals in China. Data for 421 critically ill patients were collected on December 13, 2019, and January 13, 2020, including patient characteristics, physiological, and clinical information. Logistic regression was used to analyze the risk factors for IAPI on the sacrum in the ICU.

Results

Forty‐one patients presented sacrum pressure injuries in the ICU, with a frequency of 9.74%. Risk factors that significantly increased the risk of IAPI on the sacrum were lower body mass index (BMI, odds ratio [OR] = 1.115, confidence interval [CI]: 1.011‐1.229, P = .029), chronic obstructive pulmonary disease (COPD, OR = 3.183, CI: 1.261‐8.037, P = .014), multiple organ dysfunction syndrome (MODS, OR = 2.670, CI: 1.031‐6.903, P = .043), and a lower Braden risk score (OR = 1.409, CI: 1.197‐1.659, P < .001).

Conclusion

Lower BMI, COPD, MODS, and lower Braden risk score are independent risk factors for sacrum IAPI in China.
Level and determinants of contraceptive uptake among women attending facilities with abortion‐related complications in East and Southern Africa
Authors: Qureshi Zahida , Jamner Alanna , Filippi Veronique , Gwako George , Osoti Alfred , Mehrtash Hedieh , Baguiya Adama , Bello Folasade Adenike , Compaoré Rachidatou , Gadama Luis , Kim Caron R. , Msusa Ausbert Thoko , Tunçalp Ӧzge , Calvert Clara
Published: October 2021

Objective

To investigate the level and determinants of nonreceipt of contraception among women admitted to facilities with abortion‐related complications in East and Southern Africa.

Methods

Cross‐sectional data from Kenya, Malawi, Mozambique, and Uganda collected as part of the World Health Organization (WHO) Multi‐Country Survey on Abortion‐related morbidity. Medical record review and the audio computer‐assisted self‐interviewing system were used to collect information on women's demographic and clinical characteristics and their experience of care. The percentage of women who did not receive a contraceptive was estimated and the methods of choice for different types of contraceptives were identified. Potential determinants of nonreceipt of contraception were grouped into three categories: sociodemographic, clinical, and service‐related characteristics. Generalized estimating equations were used to identify the determinants of nonreceipt of a contraceptive following a hierarchical approach.

Results

A total of 1190 women with abortion‐related complications were included in the analysis, of which 33.9% (n = 403) did not receive a contraceptive. We found evidence that urban location of facility, no previous pregnancy, and not receiving contraceptive counselling were risk factors for nonreceipt of a contraceptive. Women from nonurban areas were less likely not to receive a contraceptive than those in urban areas (AOR 0.52; 95% CI, 0.30–0.91). Compared with women who had a previous pregnancy, women who had no previous pregnancy were 60% more likely to not receive a contraceptive (95% CI, 1.14–2.24). Women who did not receive contraceptive counselling were over four times more likely to not receive a contraceptive (AOR 4.01; 95% CI, 2.88–5.59).

Conclusion

Many women leave postabortion care having not received contraceptive counselling and without a contraceptive method. There is a clear need to ensure all women receive high‐quality contraceptive information and counselling at the facility to increase contraceptive acceptance and informed decision‐making.
Hybrid pediatric and adolescent gynecology telemedicine consultation in the era of COVID‐19: Evaluation and feasibility
Authors: Giannakoulis Vassilis G. , Giannakodimos Ilias , Kalampalikis Andreas , Migklis Kyriaki , Roidi Stella , Michala Lina
Published: October 2021

Pediatric and adolescent gynecology presents unique barriers regarding the adoption of remote counseling. In this study, the authors assessed the feasibility and satisfaction of a hybrid telemedicine model which showed promising potential.
Power of a growth mindset: why certain habits of mind matter in clinical practice
Authors: Lucas Bill
Published: October 2021

This article introduces growth mindset, exploring how people grow and change, and the way that habits of the mind can influence ‘quality improvement’ (QI). In collaboration with RCVS Knowledge, whose QI campaign supports practices to embed QI concepts into their teams, this article discusses a model developed with educationalists, researchers and clinicians that can be implemented within practice to improve outcomes.
Copper induces oxidative stress and apoptosis of hippocampal neuron via pCREB/BDNF/ and Nrf2/HO‐1/NQO1 pathway
Authors: Lu Qiang , Zhang Ying , Zhao Chao , Zhang Hu , Pu Yuepu , Yin Lihong
Published: October 2021

Disordered copper metabolism has been suggested to occur to several neurological conditions, including Alzheimer's disease and Parkinson's disease. However, the underlying mechanism was still unclear. This might link to copper‐induced hippocampal neuronal apoptosis and decrease in neurons viability. Our vitro experiment showed copper exposure induced oxidative stress and promoted apoptosis of HT22 murine hippocampal neuronal cell. Mechanistically, we found copper, on the one hand, prevented phosphorylation of cAMP response element binding protein (CREB) to decrease expression its downstream target protein Brain‐derived neurotrophic factor (BDNF), and to decrease mitochondrial membrane potential and Bcl‐2/Bax ratio; on the other hand, copper‐induced reactive oxygen species (ROS), promoted lipid peroxidation, reduced antioxidant enzyme activity of GSH‐Px. Copper‐induced oxidative damage further decreased the phosphorylation of CREB, decreased expression of Bcl‐2, enhanced expression of Bax, and accelerated the dissociation of keap1‐Nrf2 complex, promoted the nuclear translocation of Nrf2, stimulate the expression of antioxidant molecules HO‐1 and NQO1. In conclusion, we found copper inhibited pCREB/BDNF signaling pathway by prevent CREB from phosphorylation, further found that oxidative damage not only inhibited neuroprotective signaling pathways and induced apoptosis, but activated antioxidant protection signals Nrf2/HO‐1/NQO1 signaling pathway.
Cefepime and diclofenac sodium combined treatment‐potentiated multiple organ injury: Role of oxidative damage and disrupted lipid metabolism
Authors: Aboubakr Mohamed , Abdelkader Afaf , Habotta Ola A. , Adel Nisreen , Emam Mahmoud A. , Abdelhiee Ehab Y. , Shanab Obeid , Shoghy Khaled , Elnoury Heba , Soliman Mohamed M. , Ibrahim Samah F. , Abdeen Ahmed
Published: October 2021

Concurrent exposure to antimicrobial and nonsteroidal anti‐inflammatory drugs (NSAIDs) is usually inevitable in most infections and postsurgery. Consequently, the present study was designed to assess the intertwining impact of coadministration of cefepime (CP, a wide spectrum antibiotic) and diclofenac sodium (DF, an NSAID) on rat's liver, kidney, and testes. Rats received saline, CP (180 mg/kg/day, IM), DF (10 mg/kg/day, IM), or a combination of CP and DF. After 14 days, CP or DF induced tissue damage expressed by marked biochemical alterations in hepatic and renal function tests. Besides this, disrupted lipid metabolism and testosterone levels along with significant histological changes in hepatic, renal, and testicular tissues were noticed. A significant increase in malondialdehyde and decreases in superoxide dismutase and catalase activities alongside significant upregulated caspase 3 expression in tissues following CP or DF treatment suggested a bearable influence of oxidative stress, lipid peroxidation, and cell death. Accordingly, the simultaneous therapy of CP and DF evoked more obvious tissue damage than their individual treatment. Overall, data concluded that concurrent use of CP and DF in medical practice is a worrisome matter, so it should be done cautiously to avoid synergistic deleterious outcomes.
A study of abnormal cannabidiols system‐mediated cardiovascular protection in disrupted gut/brain axis associated depression
Authors: Hassan Almalki Waleed
Published: October 2021

Uncontrolled stress can lead to vascular injury, hypertension, arrhythmia, compromised immune system alteration in microbiota activity, and neurobehavioral changes, including depression. The gut microbiota has been recently developed, not only for major depressive disorders but also cardiovascular problems, as a therapeutic concern. Since then, >100 studies have studied the link between depression and cardiovascular disease (CVD), and have shown that depression is common (≈20%–35%) in patients with CVD, and seems to be indicative of negative heart effects in patients. Depressive symptoms patients have demonstrated an elevated platelet reactivity, reduced cardiac variability, and enhanced proinflammatory signals, which are all cardiovascular‐related risk factors. The pathophysiology of depression‐related CVD is nevertheless a challenge because of the heterogeneous depressive syndromes and the etiologies. The cardiovascular effects of tetrahydrocannabinol (THC) (the key psychotropic credential of cannabis) and endocannabinoids (THC endogenous equivalents which cause type 1 [CB1] and 2 [CB2] cannabinoids) have been extensively examined based on well‐documented effects of marijuana smoke on blood pressure (BP) and heart rate (HR). Therefore, the aim of the review article is to establish the relationship of abnormal cannabidiols system‐mediated cardiovascular protection in disrupted gut/brain axis associated depression to determine the translational potential of targeting abnormal cannabidiols receptors in clinical studies.
Benchmark ab initio proton affinity and gas‐phase basicity of α‐alanine based on coupled‐cluster theory and statistical mechanics
Authors: Dékány Attila Á. , Czakó Gábor
Published: October 2021

We determine the proton affinity (PA) and gas‐phase basicity (GB) of amino acid α‐alanine at a chemically accurate level by performing explicitly‐correlated CCSD(T)‐F12b/aug‐cc‐pVDZ geometry optimizations and normal mode vibrational frequency calculations as well as CCSD(T)‐F12b/aug‐cc‐pVTZ energy computations at the possible neutral and protonated geometries. Temperature effects at 298.15 K considering translational, rotational, and vibrational enthalpy and entropy corrections are obtained via standard statistical mechanics utilizing the molecular geometries and the harmonic vibrational energy levels. Both the amino nitrogen (N) and the carbonyl oxygen (O) atoms are proven to be potential protonation sites and a systematic conformational search reveals 3 N‐ and 9 O‐protonated conformers in the 0.00–7.88 and 25.43–30.43 kcal/mol energy ranges at 0 K, respectively. The final computed PA and GB values at (0)298.15 K in case of N‐protonation are (214.47)216.80 and 207.07 kcal/mol, respectively, whereas the corresponding values for O‐protonation are (189.04)190.63 and 182.31 kcal/mol. The results of the benchmark high‐level coupled‐cluster computations are utilized to assess the accuracy of several lower‐level cost‐effective methods such as MP2 and density functional theory with various functionals (SOGGA11‐X, M06‐2X, PBE0, B3LYP, M06, TPSS).
Effects of mussel‐inspired co‐deposition of 2‐hydroxymethyl methacrylate and poly (2‐methoxyethyl acrylate) on the hydrophilicity and binding tendency of common hemodialysis membranes: Molecular dynamics simulations and molecular docking studies
Authors: Mollahosseini Arash , Saadati Shaghayegh , Abdelrasoul Amira
Published: October 2021

Despite advances in the field, hemoincompatibility remains a critical issue for hemodialysis (HD) as interactions between various human blood constituents and the polymeric structure of HD membranes results in complications such as activation of immune system cascades. Adding hydrophilic polymer structures to the membranes is one modification approach that can decrease the extent of protein adsorption. This study conducted molecular dynamics (MD) simulations to understand the interactions between three human serum proteins (fibrinogen [FB], human serum albumin, and transferrin) and common HD membranes in untreated and modified forms. Poly(aryl ether sulfone) (PAES) and cellulose triacetate were used as the common dialyzer polymers, and membrane modifications were performed with 2‐hydroxymethyl methacrylate (HEMA) and poly (2‐methoxyethyl acrylate) (PMEA), using polydopamine‐assisted co‐deposition. The MD simulations were used as the framework for binding energy simulations, and molecular docking simulations were also performed to conduct molecular‐level investigations between the two modifying polymers (HEMA and PMEA) and FB. Each of the three proteins acted differently with the membranes due to their unique nature and surface chemistry. The simulations show PMEA binds less intensively to FB with a higher number of hydrogen bonds, which reflects PMEA's superior performance compared to HEMA. The simulations suggest PAES membranes could be used in modified forms for blood‐contact applications as they reflect the lowest binding energy to blood proteins.