bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quinazoline‐Assisted ortho‐Halogenation with N‐Halosuccinimides through Pd(II)‐Catalyzed C(sp2)−H Activation
Authors: Wang Yong , Wang Hui , Yang Qifan , Xie Shihua , Zhu Hongjun 
Published: April 2022

AbstractAn efficient quinazoline‐assisted ortho‐halogenation of 2‐arylquinazolines has been developed using N‐halosuccinimides as halogen sources with Pd(II)‐catalyzed C−H bond activation. No additional ligand and oxidant are required. This protocol is highly regioselective and applicable to a broad range of quinazoline substrates bearing different functional groups, giving yields of up to 98 %. The mechanism of the quinazoline ortho‐halogenation was investigated by comprehensive experimentation.
Global strategy collections: Emerging market multinational enterprises
Authors: Pedersen Torben , Tallman Stephen 
Published: April 2022

AbstractResearch SummaryThis first collection of articles for global strategy focuses on the relatively new phenomenon of Emerging Market Multinational Enterprises (EMNEs). The first topic to draw real attention to articles in Global Strategy Journal, the study of EMNEs challenges many assumptions about what characteristics make a firm a successful MNE and forces a reconsideration of fundamental questions in strategic management. The articles in the collection provide a good introduction to the topic, but there is much more research on the topic in a variety of journals for those scholars considering the EMNE as a topic for their own research.Managerial summaryIn the last couple of decades, we have seen the emergence of EMNEs that are competing globally. This primer on EMNEs points at the specificities of EMNEs including their ownership‐specific advantages, their pattern of internationalization, their innovation strategies for catching‐up, and not least how their ownership and the home conditions in less developed countries alter their behavior. These are important factors that serve to help scholars to understand the strategies and actions of EMNEs and how they gain their competitive strengths on the global scene.
Mutation‐related magnetization‐transfer, not axon density, drives white matter differences in premanifest Huntington disease: Evidence from in vivo ultra‐strong gradient MRI
Authors: Casella Chiara , Chamberland Maxime , Laguna Pedro L. , Parker Greg D. , Rosser Anne E. , Coulthard Elizabeth , Rickards Hugh , Berry Samuel C. , Jones Derek K. , Metzler‐Baddeley Claudia 
Published: April 2022

AbstractWhite matter (WM) alterations have been observed in Huntington disease (HD) but their role in the disease‐pathophysiology remains unknown. We assessed WM changes in premanifest HD by exploiting ultra‐strong‐gradient magnetic resonance imaging (MRI). This allowed to separately quantify magnetization transfer ratio (MTR) and hindered and restricted diffusion‐weighted signal fractions, and assess how they drove WM microstructure differences between patients and controls. We used tractometry to investigate region‐specific alterations across callosal segments with well‐characterized early‐ and late‐myelinating axon populations, while brain‐wise differences were explored with tract‐based cluster analysis (TBCA). Behavioral measures were included to explore disease‐associated brain‐function relationships. We detected lower MTR in patients' callosal rostrum (tractometry: p = .03; TBCA: p = .03), but higher MTR in their splenium (tractometry: p = .02). Importantly, patients' mutation‐size and MTR were positively correlated (all p‐values < .01), indicating that MTR alterations may directly result from the mutation. Further, MTR was higher in younger, but lower in older patients relative to controls (p = .003), suggesting that MTR increases are detrimental later in the disease. Finally, patients showed higher restricted diffusion signal fraction (FR) from the composite hindered and restricted model of diffusion (CHARMED) in the cortico‐spinal tract (p = .03), which correlated positively with MTR in the posterior callosum (p = .033), potentially reflecting compensatory mechanisms. In summary, this first comprehensive, ultra‐strong gradient MRI study in HD provides novel evidence of mutation‐driven MTR alterations at the premanifest disease stage which may reflect neurodevelopmental changes in iron, myelin, or a combination of these.
Reliability of quantitative multiparameter maps is high for magnetization transfer and proton density but attenuated for R1 and R2* in healthy young adults
Authors: Wenger Elisabeth , Polk Sarah E. , Kleemeyer Maike M. , Weiskopf Nikolaus , Bodammer Nils C. , Lindenberger Ulman , Brandmaier Andreas M. 
Published: April 2022

AbstractWe investigate the reliability of individual differences of four quantities measured by magnetic resonance imaging‐based multiparameter mapping (MPM): magnetization transfer saturation (MT), proton density (PD), longitudinal relaxation rate (R1), and effective transverse relaxation rate (R2*). Four MPM datasets, two on each of two consecutive days, were acquired in healthy young adults. On Day 1, no repositioning occurred and on Day 2, participants were repositioned between MPM datasets. Using intraclass correlation effect decomposition (ICED), we assessed the contributions of session‐specific, day‐specific, and residual sources of measurement error. For whole‐brain gray and white matter, all four MPM parameters showed high reproducibility and high reliability, as indexed by the coefficient of variation (CoV) and the intraclass correlation (ICC). However, MT, PD, R1, and R2* differed markedly in the extent to which reliability varied across brain regions. MT and PD showed high reliability in almost all regions. In contrast, R1 and R2* showed low reliability in some regions outside the basal ganglia, such that the sum of the measurement error estimates in our structural equation model was higher than estimates of between‐person differences. In addition, in this sample of healthy young adults, the four MPM parameters showed very little variability over four measurements but differed in how well they could assess between‐person differences. We conclude that R1 and R2* might carry only limited person‐specific information in some regions of the brain in healthy young adults, and, by implication, might be of restricted utility for studying associations to between‐person differences in behavior in those regions.
Change in parathyroid hormone levels from baseline predicts hypocalcemia following total or completion thyroidectomy
Authors: Swift William M. , Iorio Caitlin B. , Hamdi Osama A. , Mallawaarachchi Indika , Wages Nolan A. , Shonka David C. 
Published: April 2022

AbstractBackgroundThis study aims to identify the strongest predictor of postoperative hypocalcemia following thyroid surgery.MethodsStudy of patients who underwent total/completion thyroidectomy. No patients received postoperative calcium supplementation. Demographic and perioperative data were collected including preoperative baseline parathyroid hormone (PTH) levels, PTH levels at 30 min and 6 h post‐excision, and 18 h post‐excision calcium levels.ResultsOf 124 patients studied, 20.2% developed temporary hypocalcemia (Ca <8.5 mg/dL at 18 h post‐excision). In multivariate analyses, absolute PTH levels at 30 min and 6 h post‐excision as well as change in PTH from baseline at 30 min and 6 h post‐excision were statistically significantly associated with postoperative hypocalcemia. Per 10 units decrease in PTH from baseline at 30 min post‐excision, the risk of developing temporary hypocalcemia increases by 17%.ConclusionAbsolute PTH levels and change in PTH from baseline at 30 min and 6 h post‐excision predict hypocalcemia after total or completion thyroidectomy.
Implementation of guidelines about women with previous cesarean section through educational/motivational interventions
Authors: Monari Francesca , Menichini Daniela , Bertucci Emma , Neri Isabella , Perrone Enrica , Facchinetti Fabio 
Published: April 2022

AbstractObjectiveTo investigate the effect of a quality improvement project with an educational/motivational intervention in northern Italy on the implementation of the trial of labor after cesarean section (CS).MethodA pre‐post study design was used. Every birth center (n = 23) of the Emilia‐Romagna region was included. Gynecologist opinion leaders were first trained about Italian CS recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected during two periods, before (2012–2014) and after (2017–2019) the intervention (2015–2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes.ResultsA total of 20 496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (P < 0.001). The likelihood of VBAC—adjusted for age 40 years or older, Caucasian, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) at least 30, previous vaginal delivery, and labor induction—was increased by the intervention by 42% (odds ratio 1.42, 95% confidence interval 1.31–1.54). Neonatal well‐being was improved by intervention; neonates requiring resuscitation decreased from 2.1% to 1.6% (P = 0.001).ConclusionEducating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well‐being.
Bonding character of intermediates in on‐surface Ullmann reactions revealed with energy decomposition analysis
Authors: Luy Jan‐Niclas , Henkel Pascal , Grigjanis Daniel , Jung Jannis , Mollenhauer Doreen , Tonner‐Zech Ralf 
Published: April 2022

AbstractOn‐surface synthesis has become a thriving topic in surface science. The Ullmann coupling reaction is the most applied synthetic route today, but the nature of the organometallic intermediate is still under discussion. We investigate the bonding nature of prototypical intermediate species (phenyl, naphthyl, anthracenyl, phenanthryl, and triphenylenyl) on the Cu(111) surface with a combination of plane wave and atomic orbital basis set methods using density functional theory calculations with periodic boundary conditions. The surface bonding is shown to be of covalent nature with a polarized shared‐electron bond supported by π‐back donation effects using energy decomposition analysis for extended systems (pEDA). The bond angle of the intermediates is determined by balancing dispersion attraction and Pauli repulsion between adsorbate and surface. The latter can be significantly reduced by adatoms on the surface. We furthermore investigate how to choose computational parameters for pEDA of organic adsorbates on metal surfaces efficiently and show that bonding interpretation requires consistent choice of the density functional.
Circular RNA hsa_circ_0011298 enhances Taxol resistance of non‐small cell lung cancer by regulating miR‐486‐3p/CRABP2 axis
Authors: Wu Yihong , Xie Jieyun , Wang Han , Hou Shufang , Feng Jiuhuan 
Published: April 2022

AbstractBackgroundCircular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non‐small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC.MethodsCirc_0011298, microRNA‐486‐3p (miR‐486‐3p), and CRABP2 mRNA expression were determined using qRT‐PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual‐luciferase reporter and RIP assays were performed to confirm the relationship between miR‐486‐3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo.ResultsCirc_0011298 was overexpressed in Taxol‐resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol‐resistant NSCLC cells. Circ_0011298 was a sponge of miR‐486‐3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR‐486‐3p inhibition. Moreover, miR‐486‐3p directly targeted CRABP2, and miR‐486‐3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR‐486‐3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo.ConclusionCirc_0011298 elevated Taxol resistance of NSCLC by sponging miR‐486‐3p and upregulating CRABP2, providing a possible circRNA‐targeted therapy for NSCLC.
Drug‐Drug Interactions and Disease Status Are Associated With Irinotecan‐Induced Hepatotoxicity: A Cross‐Sectional Study in Shanghai
Authors: Li Juan , Chen Bing , Xi Wen‐qi , Jia Wan , Zhang Wei‐xia , Bian Xiao‐lan 
Published: April 2022

AbstractIrinotecan‐induced hepatotoxicity can cause severe clinical complications in patients; however, the underlying mechanism and factors affecting hepatotoxicity have rarely been investigated. In this cross‐sectional study, we screened all clinical, demographic, medication, and genetic variables among 126 patients receiving irinotecan and explored potential associations with the incidence and time to onset of irinotecan‐induced hepatotoxicity. Approximately 38.9% of the patients suffered from hepatotoxicity after irinotecan administration. The presence of cardiovascular diseases increases the incidence of hepatotoxicity ≈2.9‐fold and doubles the hazard of time to hepatotoxicity. Patients with liver metastasis had a >4‐fold higher risk of hepatotoxicity and a 3.5‐fold increased hazard of time to hepatotoxicity compared to those without liver metastasis. Patients who took cytochrome P450 (CYP) 3A inducers had a 4.4‐fold increased incidence of hepatotoxicity, and furthermore, concomitant use of platinum‐based antineoplastics revealed 4.2 times the hazard of time to hepatotoxicity compared to those receiving antimetabolites. The cumulative dose of irinotecan (5‐9 cycles) increased hepatotoxicity by 8.5 times. However, the genotypes and phenotypes of UGT1A1*28/*6 failed to be predictive factors of hepatotoxicity. The findings of this study suggest that irinotecan‐induced hepatotoxicity is not directly associated with genetic variables but is mostly related to concomitant use of CYP3A4 inducers and platinum, as well as the presence of liver metastasis and cardiovascular disease. Thus, close monitoring of liver function is recommended, especially in patients with liver impairment or using CYP3A inducers and platinum antineoplastic drugs, which may be the best way to prevent hepatotoxicity.
Formation of algal flocs from activated sludge in synthetic medium and secondary treated wastewater
Authors: Biliani Styliani E , Manariotis Ioannis D 
Published: April 2022

AbstractBACKGROUNDPhotogranules seem to be an alternative solution for wastewater treatment and biomass harvesting. The aim of our work was to investigate the formation of algal flocs as an efficient method for the treatment of wastewater and separation of algal cells.RESULTSThe progressive change of activated sludge to algal flocs was evaluated under static and stirring conditions using a synthetic substrate (modified Blue Green‐11 medium) and the secondary effluent from an activated sludge wastewater treatment plant. Algal flocs were observed in all cultures by day 10 and a high chlorophyll concentration was detected in all cases reaching values up to 610–630 μg L−1 at the end of the experiment after 30 days. The size of flocs in all cultures at either static or mixing conditions ranged from 330 to 994 μm, resulting in biomass concentration from 330 to 660 mg L−1. The cultures in secondary effluent at static conditions presented the greatest size, and the mean diameter on days 10 and 30 was 250 and 994 μm, respectively. The cultures were efficient in nutrient removal and, by the end of the experiment, nitrates and phosphates were completely consumed.CONCLUSIONSAlgal flocs were developed from activated sludge without adding any other flocculant and a highly efficient biomass was developed, which can easily settle and remove nutrients from the medium. © 2022 Society of Chemical Industry (SCI).
Association of alkaptonuria and low dose nitisinone therapy with cataract formation in a large cohort of patients
Authors: Ahmad Mohammad S. Z. , Ahmed Mahmoud , Khedr Milad , Borgia Alfredo , Madden Andrea , Ranganath Lakshminarayan R. , Kaye Stephen 
Published: April 2022

AbstractHomogentisic acid (HGA) lowering, disease modifying off‐label nitisinone therapy has been used in the United Kingdom National Alkaptonuria Centre (NAC) since 2012. This study evaluated the serendipitous observation of cataract in a large cohort of patients with the very rare disease alkaptonuria (AKU), over a 5‐year period. Patients with AKU who attended the NAC since 2012. Standard physical examination and ocular assessment, including photographs of the crystalline lens were taken before commencement of nitisinone 2 mg daily and annually over 5 years. Photographs were randomised and graded by two independent observers using the WHO cataract classification. AKU patients who did not receive nitisinone were included as a control group. HGA was measured on acidified 24 h urine (u‐HGA24) and HGA and tyrosine in fasting acidified serum samples (sHGA, sTYR) at each visit. Patients without suitable lens images were excluded. Cataract (mean grade 1) was noted at baseline in 47 out of 62 (76%) with a mean (SD) age of 44 (14) years. In nitisinone‐treated patients, there were significant increases in the mean grade of nuclear (0.18, p < 0.01) and cortical (0.38, p < 0.01) lens opacities over the mean duration of 4.93 years of the study. Worsening of the nuclear cataract and cortical lens opacities by at least 1 grade was noted in 14 out of 46 (30%) and 11 out of 46 (24%) patients, respectively. There is an increased prevalence and progression of cataract in AKU and a possible association of nitisinone with cataract progression.
Investigation of the Inter‐ and Intrascanner Reproducibility and Repeatability of Radiomics Features in T1‐Weighted Brain MRI
Authors: Mitchell‐Hay Rosalind Nina , Ahearn Trevor S. , Murray Alison D. , Waiter Gordon D. 
Published: April 2022

BackgroundRadiomics is the high throughput analysis of medical images using computer algorithms, which specifically assess textural features. It has increasingly been proposed as a tool for the development of imaging biomarkers. However, an important acknowledged limitation of radiomics is the lack of reproducibility of features produced.PurposeTo assess reproducibility and repeatability of radiomics variables in brain MRI through a multivisit, multicenter study.Study TypeRetrospective.PopulationFourteen individuals visiting three institutions twice, 10 males with the mean age of 36.3 years and age range 25–51.Field Strength3D T1W inversion recovery on three 1.5‐T General Electric scanners.AssessmentRadiomics analysis by a consultant radiologist performed on the T1W images of the whole brain on all visits. All possible radiomics features were generated.Statistical TestConcordance correlation coefficient (CCC) and dynamic range (DR) for all variables were calculated to assess the test–retest repeatability. Intraclass correlation coefficients (ICCs) were calculated to investigate the reproducibility of features across centers.ResultsOf 1596 features generated, 57 from center 1, 15 from center 2, and 22 from center 3 had a CCC > 0.9 and DR > 0.9. Eight variables had CCC > 0.9 and DR > 0.9 in all centers. Forty‐one variables had an ICC of >0.9. No variables had CCC > 0.9, DR > 0.9, and ICC > 0.9.Data ConclusionRepeatability and reproducibility of variables is a significant limitation of radiomics analysis in 3DT1W brain MRI. Careful selection of radiomic features is required.Level of Evidence4Technical Efficacy Stage2
Cerebrovascular Reactivity Mapping Using Resting‐State Functional MRI in Patients With Gliomas
Authors: Yeh Mei‐Yu , Chen Henry S. , Hou Ping , Kumar Vinodh A. , Johnson Jason M. , Noll Kyle R. , Prabhu Sujit S. , Ferguson Sherise D. , Schomer Donald F. , Peng Hsu‐Hsia , Liu Ho‐Ling 
Published: April 2022

BackgroundRecently, a data‐driven regression analysis method was developed to utilize the resting‐state (rs) blood oxygenation level–dependent signal for cerebrovascular reactivity (CVR) mapping (rs‐CVR), which was previously optimized by comparing with the CO2 inhalation‐based method in health subjects and patients with neurovascular diseases.PurposeTo investigate the agreement of rs‐CVR and the CVR mapping with breath‐hold MRI (bh‐CVR) in patients with gliomas.Study TypeRetrospective.PopulationTwenty‐five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas.Field Strength/SequenceDynamic T2*‐weighted gradient‐echo echo‐planar imaging during a breath‐hold paradigm and during the rs on a 3‐T scanner.Assessmentrs‐CVR with various frequency ranges and resting‐state fluctuation amplitude (RSFA) were assessed. The agreement between each rs‐based CVR measurement and bh‐CVR was determined by voxel‐wise correlation and Dice coefficient in the whole brain, gray matter, and the lesion region of interest (ROI).Statistical TestsVoxel‐wise Pearson correlation, Dice coefficient, Fisher Z‐transformation, repeated‐measure analysis of variance and post hoc test with Bonferroni correction, and nonparametric repeated‐measure Friedman test and post hoc test with Bonferroni correction were used. Significance was set at P < 0.05.ResultsCompared with bh‐CVR, the highest correlations were found at the frequency bands of 0.04–0.08 Hz and 0.02–0.04 Hz for rs‐CVR in both whole brain and the lesion ROI. RSFA had significantly lower correlations than did rs‐CVR of 0.02–0.04 Hz and a wider frequency range (0–0.1164 Hz). Significantly higher correlations and Dice coefficient were found in normal tissues than in the lesion ROI for all three methods.Data ConclusionThe optimal frequency ranges for rs‐CVR are determined by comparing with bh‐CVR in patients with gliomas. The rs‐CVR method outperformed the RSFA. Significantly higher correlation and Dice coefficient between rs‐ and bh‐CVR were found in normal tissue than in the lesion.Level of Evidence3Technical Efficacy Stage2