bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parametric and Nonparametric Methods in Population Pharmacokinetics: Experts’ Discussion on Use, Strengths, and Limitations
Authors: Goutelle Sylvain , Woillard Jean‐Baptiste , Buclin Thierry , Bourguignon Laurent , Yamada Walter , Csajka Chantal , Neely Michael , Guidi Monia 
Published: October 2021

AbstractPopulation pharmacokinetics consists of analyzing pharmacokinetic (PK) data collected in groups of individuals. Population PK is widely used to guide drug development and to inform dose adjustment via therapeutic drug monitoring and model‐informed precision dosing. There are 2 main types of population PK methods: parametric (P) and nonparametric (NP). The characteristics of P and NP population methods have been previously reviewed. The aim of this article is to answer some frequently asked questions that are often raised by scholars, clinicians, and researchers about P and NP population PK methods. The strengths and limitations of both approaches are explained, and the characteristics of the main software programs are presented. We also review the results of studies that compared the results of both approaches in the analysis of real data. This opinion article may be informative for potential users of population methods in PK and guide them in the selection and use of those tools. It also provides insights on future research in this area.
Adverse muscle composition predicts all‐cause mortality in the UK Biobank imaging study
Authors: Linge Jennifer , Petersson Mikael , Forsgren Mikael F. , Sanyal Arun J. , Dahlqvist Leinhard Olof 
Published: October 2021

AbstractBackgroundAdverse muscle composition (MC) as measured by magnetic resonance imaging has previously been linked to poor function, comorbidity, and increased hospitalization. The aim of this study was to investigate if adverse MC predicts all‐cause mortality using data from UK Biobank.MethodsThere were 40 178 participants scanned using a 6 min magnetic resonance imaging protocol. Images were analysed for thigh fat‐tissue free muscle volume and muscle fat infiltration (MFI) using AMRA® Researcher (AMRA Medical, Linköping, Sweden). For each participant, a sex, weight, and height invariant muscle volume z‐score was calculated. Participants were partitioned into four MC groups: (i) normal MC, (ii) only low muscle volume [<25th percentile for muscle volume z‐score (population wide)], (iii) only high MFI [>75th percentile (population wide, sex‐specific)], and (iv) adverse MC (low muscle volume z‐score and high MFI). Association of MC groups with mortality was investigated using Cox proportional‐hazard modelling with normal MC as referent (unadjusted and adjusted for low hand grip strength, sex, age, body mass index, previous diagnosis of disease (cancer, type 2 diabetes and coronary heart disease), lifestyle, and socioeconomic factors (smoking, alcohol consumption, physical activity, and Townsend deprivation index).ResultsMuscle composition measurements were complete for 39 804 participants [52% female, mean (SD) age 64.2 (7.6) years and body mass index 26.4 (4.4) kg/m2]. Three hundred twenty‐eight deaths were recorded during a follow‐up period of 2.9 (1.4) years after imaging. At imaging, adverse MC was detected in 10.5% of participants. The risk of death from any cause in adverse MC compared with normal MC was 3.71 (95% confidence interval 2.81–4.91, P < 0.001). Only low muscle volume and only high MFI were independently associated with all‐cause mortality [1.58 (1.13–2.21), P = 0.007, and 2.02 (1.51–2.71), P < 0.001, respectively]. Adjustment of low hand grip strength [1.77 (1.28–2.44), P < 0.001] did not attenuate the associations with any of the MC groups. In the fully adjusted model, adverse MC and only high MFI remained significant (P < 0.001 and P = 0.020) while the association with only low muscle volume was attenuated to non‐significance (P = 0.560). The predictive performance of adverse MC [1.96 (1.42–2.71), P < 0.001] was comparable with that of previous cancer diagnosis [1.93 (1.47–2.53), P < 0.001] and smoking [1.71 (1.02–2.84), P = 0.040]. Low hand grip strength was borderline non‐significant [1.34 (0.96–1.88), P = 0.090].ConclusionsAdverse MC was a strong and independent predictor of all‐cause mortality. Sarcopenia guidelines can be strengthened by including cut‐offs for myosteatosis enabling detection of adverse MC.
The impact of COVID‐19 on multi‐month dispensing (MMD) policies for antiretroviral therapy (ART) and MMD uptake in 21 PEPFAR‐supported countries: a multi‐country analysis
Authors: Bailey Lauren E. , Siberry George K. , Agaba Patricia , Douglas Meaghan , Clinkscales Jessica R. , Godfrey Catherine 
Published: October 2021

AbstractIntroductionIncreasing access to multi‐month dispensing (MMD) of antiretroviral therapy (ART) supports treatment continuity and viral load suppression for people living with HIV (PLHIV) and reduces burden on health facilities. During the COVID‐19 response, PEPFAR worked with ministries of health to scale up MMD and expand eligibility to new groups of PLHIV, including children and pregnant/breastfeeding women. We analysed PEPFAR program data to understand the impact of the policy changes on actual practice.MethodsWe conducted a desk review in 21 PEPFAR‐supported countries to identify and collect official documentation released between March and June 2020 addressing changes to MMD guidance during the COVID‐19 response. MMD coverage, the proportion of all ART clients on MMD, was assessed in the calendar quarters preceding the COVID‐19 response (Q4 2019, October–December 2019; and Q1, January–March 2020) and the quarters following the start of the response (Q2 2020, April–June 2020; Q3 2020, July–September, 2020; Q4 2020, October–December 2020). We used the two‐proportion Z‐test to test for differences in MMD coverage pre‐COVID‐19 (Q4 2019) and during implementation of COVID‐19 policy adaptations (Q2 2020).Results and discussionAs of June 2020, 16 of the 21 PEPFAR‐supported countries analysed adapted MMD policy or promoted intensified scale‐up of MMD in response to COVID‐19. MMD coverage for all clients on ART grew from 49% in Q4 2019 pre‐COVID‐19 to 72% in Q2 2020 during COVID‐19; among paediatric clients (< 15), MMD coverage increased from 27% to 51% in the same period. Adaptations to MMD policy were associated with a significantly accelerated growth in the proportion of clients on MMD (p < 0.001) for all populations, irrespective of age and dispensing interval.ConclusionsAccess to MMD markedly expanded during the COVID‐19 pandemic, supporting treatment continuity while mitigating exposure to COVID‐19 at health facilities. This model is beneficial in public health emergencies and during disruptions to the healthcare system. Outside emergency contexts, expanded MMD eligibility extends client‐centred care to previously excluded populations. The success in expanding MMD access during COVID‐19 should motivate countries to recommend broader MMD access as a new standard of care.
Study on aqueous film‐forming foam extinguishing agent based on fluorocarbon cationic–hydrocarbon anionic surfactants mixture system
Authors: Yang Yawen , Peng Mengyuan , Sha Min , Fang Jiaqing , Zhang Ding , Pan Renming , Jiang Biao 
Published: October 2021

AbstractFluorocarbon surfactants were the main components of aqueous film‐forming foam extinguishing agents (AFFF). Unfortunately, the widely used fluorocarbon surfactant perfluorooctane sulfonate (PFOS) was limited due to its toxicity, bioaccumulation and biodegradability. In this paper, an environmentally friendly quaternary ammonium cationic fluorocarbon surfactant with high surface activity and simple synthesis route was reported. The surface performance and aggregation behavior of the mixed solution of this fluorocarbon surfactant and sodium n‐octyl sulfate were studied by means of surface tension meter and transmission electron microscope (TEM). The results showed that the synergistic effect of sodium n‐octyl sulfate and this fluorocarbon surfactant was significant, and many vesicles could be observed in the mixed solution with the concentration of 0.1 mol/L under TEM. Subsequently, three environmental friendly AFFF formulations (F‐1, F‐2, F‐3) were designed with the mixture of the fluorocarbon surfactant, sodium n‐octyl sulfate and lauryl betaine BS‐12 as foaming agent. Through its foam performance test, it could be seen that F‐3 showed relatively excellent foam performance. The initial foam height h0 was 70 mm, the 25% drainage time was 315 s, the extinguishing time was 28 s, and the burn‐back time was 720 s. This kind of fire extinguishing agent had the potential of fire protection application.
Shear Wave Elastography and Quantitative Ultrasound as Biomarkers to Characterize Deep Vein Thrombosis In Vivo
Authors: Bosio Guillaume , Zenati Nora , Destrempes François , Chayer Boris , Pernod Gilles , Cloutier Guy 
Published: October 2021

ObjectiveInvestigate shear wave elastography (SWE) and quantitative ultrasound (QUS) parameters in patients hospitalized for lower limb deep vein thrombosis (DVT).MethodSixteen patients with DVT were recruited and underwent SWE and radiofrequency data acquisitions for QUS on day 0, day 7, and day 30 after the beginning of symptoms, in both proximal and distal zones of the clot identified on B‐mode scan. SWE and QUS features were computed to differentiate between thrombi at day 0, day 7, and day 30 following treatment with heparin or oral anticoagulant. The Young's modulus from SWE was computed, as well as QUS homodyned K‐distribution (HKD) parameters reflecting blood clot structure. Median and interquartile range of SWE and QUS parameters within clot were taken as features.ResultsIn the proximal zone of the clot, the HKD ratio of coherent‐to‐diffuse backscatter median showed a significant decrease from day 7 to day 30 (P = .036), while the HKD ratio of diffuse‐to‐total backscatter median presented a significant increase from day 7 to day 30 (P = .0491). In the distal zone of the clot, the HKD normalized intensity of the echo envelope median showed a significant increase from day 0 to day 30 (P = .0062). No SWE features showed statistically significant differences over time. Nonetheless, a trend of lower median of Young's modulus within clot for patients who developed a pulmonary embolism was observed.ConclusionQUS features may be relevant to characterize clot's evolution over time. Further analysis of their clinical interpretation and validation on a larger dataset would deserve to be studied.
Transferrin Receptor Targeted Polyplexes Completely Comprised of Sequence‐Defined Components
Authors: Benli‐Hoppe Teoman , Göl Öztürk Şurhan , Öztürk Özgür , Berger Simone , Wagner Ernst , Yazdi Mina 
Published: October 2021

AbstractHuman transferrin protein (Tf) modified polyplexes have already displayed encouraging potential for receptor‐mediated nucleic acid delivery into tumors. The use of a blood‐derived targeting protein and polydisperse macromolecular cationic subunits however presents a practical challenge for pharmaceutical grade production. Here, Tf receptor (TfR) targeted small interfering RNA (siRNA) polyplexes are designed that are completely composed of synthetic, monodisperse, and sequence‐defined subunits generated by solid‐phase supported synthesis. An optimized cationizable lipo‐oligoaminoamide (lipo‐OAA) is used for siRNA core polyplex formation, and a retro‐enantio peptide (reTfR) attached via a monodisperse polyethylene glycol (PEG) spacer via click chemistry is applied for targeting. Improved gene silencing is demonstrated in TfR‐expressing KB and DU145 cells. Analogous plasmid DNA (pDNA) polyplexes are successfully used for receptor‐mediated gene delivery in TfR‐rich K562 cells and Neuro2a cells. Six lipo‐OAAs differing in their lipidic domain and redox‐sensitive attachment of lipid residues are tested in order to evaluate the impact of core polyplex stability on receptor‐dependent gene transfer.
Effects of different imidazole accelerators on curing behavior and cross‐linked network of epoxy resin/phenolic resin/benzoxazine ternary system
Authors: Gou Haolan , Zhao Yingying , Zhou Yanglong , Wei Wei , Fei Xiaoma , Li Xiaojie , Liu Xiaoya 
Published: October 2021

AbstractFor the molding compounds used in electronic packaging, curing accelerators play a significant effect on the curing behavior of thermosetting resins, thus the cross‐linked structure and performance of the cured product. In this study, nine commercially available imidazole compounds, divided into three types, were introduced into a polyfunctional epoxy resin (E1)/XYLOK phenolic resin (P1)/MDA benzoxazine (B1) ternary system to reduce the curing temperature for molding processing. To understand the cross‐linked structure of the cured product, the ternary system was divided into unitary system and binary system, and the curing behavior and chemical structure of each system was monitored by differential scanning calorimetry and Fourier transform‐infrared systematically. Due to the nucleophilicity of tertiary amines influenced by the steric hindrance effect, it was discovered that the reaction activity of epoxy resin initiated by nine imidazole compounds, was significantly different. However, the ring opening of benzoxazine occurs at a high temperature, even catalyzed with imidazoles, and its curing behavior was nearly the same owing to the unique ring‐opening mechanism initiated by active hydrogen of imidazole. In addition, phenolic resin elevates reaction activity for both epoxy resin and benzoxazine. The cross‐linked structure of E1P1B1 ternary system was proposed based on the experimental results from each system. It suggested that the formed network of the E1P1B1 cured product with Type I and II imidazoles is mainly IPN structure, while the cured products of E1P1B1 + Type III is the copolymerization of epoxy, phenolic and benzoxazine. This paper systematically illustrated the ideal chemical structures of epoxy resin/phenolic resin/benzoxazine ternary system with different imidazole compounds, which is valuable for industrial application of resin‐based materials.
Factors associated with upper limb function in breast cancer survivors
Authors: Roldán‐Jiménez Cristina , Martín‐Martín Jaime , Pajares Bella , Ribelles Nuria , Alba Emilio , Cuesta‐Vargas Antonio I. 
Published: October 2021

AbstractBackgroundBreast cancer survivors may have side effects from treatment, such as impaired upper limb function after surgery, which may be affected by a range of factors.ObjectiveTo analyze the association between upper limb function and strength, fear avoidance, and central sensitization symptoms among breast cancer survivors, and to explore how these variables are associated with upper limb function.DesignValidation cohort.SettingInstitutional practice at a public hospital.PatientsOne hundred seventy‐four breast cancer survivors who had been undergone surgery for a primary tumor.InterventionsNot applicable.Main Outcome MeasureUpper limb function was measured by the Upper Limb Functional Index (ULFI‐Sp). Independent outcomes were: handgrip strength, which was measured using a Jamar dynamometer on the dominant side; fear avoidance, measured using the Fear‐Avoidance Components Scale (FACS‐Sp); and central sensitization symptoms, which were measured using the Central Sensitisation Inventory (CSI‐Sp). A linear regression model explaining the ULFI‐Sp results was constructed with the variables.ResultsThe regression model was significant (F = 46.826; p < .0001), and explained 45% of the variance of the ULFI values. All variables showed strong associations with upper limb function.ConclusionsGreater upper limb function is associated with higher grip strength, lower fear‐avoidance behavior and fewer central sensitization symptoms among breast cancer survivors. These variables explained 45% of the upper limb function in the regression model, and concur with earlier research showing that factors such as central sensitization symptoms and kinesiophobia negatively affect upper limb function in such patients. Clinicians should therefore take into account strength, fear avoidance, and central sensitization symptoms when considering interventions aimed at improving upper limb function among breast cancer survivors.
The mechanochemical Friedel‐Crafts polymerization as a solvent‐free cross‐linking approach toward microporous polymers
Authors: Krusenbaum Annika , Geisler Jonathan , Kraus Fabien Joel Leon , Grätz Sven , Höfler Mark Valentin , Gutmann Torsten , Borchardt Lars 
Published: October 2021

AbstractHerein we report the mechanochemical Friedel‐Crafts alkylation of 1,3,5‐triphenylbenzene (TPB) with two organochloride cross‐linking agents, dichloromethane (DCM) and chloroform (CHCl3), respectively. During a thorough milling parameter evaluation, the DCM‐linked polymers were found to be flexible and extremely sensitive toward parameter changes, which even enables the synthesis of a polymer with a SSABET of 1670 m2/g, on par with the solution‐based reference. Contrary, CHCl3‐linked polymers are exhibiting a rigid structure, with a high porosity that is widely unaffected by parameter changes. As a result, a polymer with a SSABET of 1280 m2/g could be generated in as little as 30 minutes, outperforming the reported literature analogue in terms of synthesis time and SSABET. To underline the environmental benefits of our fast and solvent‐free synthesis approach, the green metrics are discussed, revealing an enhancement of the mass intensity, mass productivity and the E‐factor, as well as of synthesis time and the work‐up in comparison to the classical synthesis. Therefore, the mechanochemical polymerization is presented as a versatile tool, enabling the generation of highly porous polymers within short reaction times, with a minimal use of chlorinated cross‐linker and with the possibility of a post polymerization modification.
Selenophene‐containing conjugated polymers for supercapacitor electrodes
Authors: Yıldız Dilber Esra , Cevher Duygu , Yasa Mustafa , Cirpan Ali , Toppare Levent 
Published: October 2021

AbstractIn recent years, studies on conjugated polymers have strengthened the researchers' thought that such polymers can play an essential role in developing new generation energy storage devices. Hence conjugated polymer supercapacitor studies have accelerated. In the present work, selenophene‐containing conjugated polymers previously synthesized via palladium‐catalyzed Suzuki polymerization reaction were used in the preparation of conjugated polymer‐based supercapacitor electrodes. The structure and surface morphology of conjugated polymers were determined using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The selenophene‐containing two conjugated polymer electrodes (ITO/Polymer) were fabricated. The electrochemical behavior of the conjugated polymer electrodes was evaluated through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The specific capacity of ITO/CP1 electrode at 5 mV/s are 161.2 and 47 (Fg−1) for 0.1 mg and 1.2 mg, respectively. The specific capacity of ITO/CP2 at 5 mV/s electrode are 511 and 108.85 (Fg−1) for 0.08 mg and 0.70 mg, respectively. The time constants were determined as 10 and 625 ms for ITO/CP1 and CP2/ITO electrodes, respectively.
Cavitary lung lesions in a neonate: Potential manifestation of COVID‐19 related multisystem inflammatory syndrome
Authors: Bakhle Anish , Sreekumar Kavita , Baracho Bonny , Sardessai Sanjay , Silveira Maria Piedade 
Published: October 2021

AbstractBackgroundThe hyperinflammatory state of multisystem inflammatory syndrome in children (MIS‐C) predisposes to thromboembolic complications. We report a neonate with multiple cavitary lesions in lung, which we suspect could be a manifestation of multisystem inflammatory syndrome in neonate (MIS‐N) following maternal COVID‐19 infection during pregnancy.Case ReportEight‐day‐old neonate was referred with fever and fast breathing. Mother was positive for COVID‐19 in 29th week. COVID‐19 reverse‐transcription polymerase chain reaction was negative, however, antibodies were positive. He had increased leucocyte count, and elevated levels of C‐reactive protein (CRP), procalcitonin, ferritin, lactate dehydrogenase, and d‐dimer along with bilateral reticulonodular opacities on chest radiograph and multiple nodules with evidence of cavitation in both lungs on chest tomography. All cultures were negative. A possible diagnosis of MIS was made. Infant was treated with intravenous immunoglobulin (IVIG) which he responded to with resolution of symptoms.ConclusionNeonates exposed to COVID‐19 should be evaluated for thromboembolic complications and IVIG can be one of the treatment modalities.
Transgenic double‐stranded RNA rice, a potential strategy for controlling striped stem borer (Chilo suppressalis)
Authors: Mao Cui , Zhu Xiaoping , Wang Peipei , Sun Yajie , Huang Renliang , Zhao Mingchao , Hull J Joe , Lin Yongjun , Zhou Fei , Chen Hao , Ma Weihua 
Published: October 2021

AbstractBACKGROUNDAlthough the striped stem borer (SSB, Chilo suppressalis Walker) is a devastating pest of rice that causes significant economic losses, management options are currently limited. Plant‐mediated RNA interference (RNAi) is an emerging crop protection technique in which transgenic plants are modified to express insect‐specific double‐stranded RNAs (dsRNAs) that trigger RNAi silencing in target pests.RESULTIn this study, an RNAi‐based screen of 35 candidate SSB genes identified a small heat shock protein gene (CssHsp) as a potential plant‐based RNAi target. To assess its utility in planta, a total of 39 transgenic rice plants were generated, with 11 independent transformants found to contain a single copy of the dsCssHsp expression cassette. In life‐time feeding bioassays, three transgenic lines (DS10, DS35, DS36) were found to have significant negative impacts on SSB populations. After feeding for 8 days, mortality in the three transgenic lines exceeded 60%. By pupation, mortality further increased to 90% and few SSB survived to eclosion. Gene expression analyses confirmed that CssHsp transcript levels were significantly reduced after feeding on the transgenic dsCssHsp rice.CONCLUSIONThese results demonstrate the potential for developing a plant‐mediated RNAi strategy targeting CssHsp as a more biorational field‐based approach for SSB control. © 2021 Society of Chemical Industry.
Sensitivity of a simple atmospheric model to changing surface friction with implications for seasonal prediction
Authors: Wicker Wolfgang , Greatbatch Richard J. , Claus Martin 
Published: October 2021

AbstractAn ensemble of idealized experiments with the simplified general circulation model PUMA is used to analyze the response to reduced surface friction, that is a strengthening of the eddy‐driven jet, a weakening of the Eulerian mean overturning, and a suppression of baroclinic instability. The suppression of baroclinic instability is caused by an effect called the barotropic governor by which increased horizontal shear restricts the ability of baroclinic disturbances to convert available potential energy into kinetic energy. This governor effect ensures that the residual circulation and Eliassen–Palm flux (EP flux) divergence are largely invariant to the surface friction parameter despite the connection between surface friction, the Eulerian mean overturning, and the eddy‐momentum flux. The suppression of instability leads to an increase in persistence measured by the period of peak variance on synoptic time‐scales and a strengthened signal‐to‐noise ratio on seasonal time‐scales. These findings suggest that the signal‐to‐noise paradox seen in the context of seasonal prediction can be caused by excess mechanical damping in atmospheric prediction systems inhibiting the barotropic governor effect.