bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considerations and Challenges in the Remdesivir COVID‐19 Pediatric Development Program
Authors: Chan‐Tack Kirk , Sampson Mario , Earp Justin , Arya Vikram , Yao Lynne , Alexander John , Hausman Ethan , Belew Yodit , Birnkrant Debra , Struble Kimberly 
Published: September 2022

AbstractThe US Food and Drug Administration is committed to the development of effective antiviral regimens for pediatric patients with coronavirus disease 2019 (COVID‐19), including infants and neonates. On April 25, 2022, the approved indication of remdesivir (RDV) was expanded to include pediatric patients 28 days and older and weighing at least 3 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 viral testing, who are:

Hospitalized, or
Not hospitalized and have mild to moderate COVID‐19 and are at high risk for progression to severe COVID‐19, including hospitalization or death.Given the similar course of COVID‐19 in adults and pediatric patients, the approval of RDV for use in pediatric patients is supported by the safety and efficacy data from adequate and well‐controlled phase 3 trials in adults and adolescents; and by the safety and pharmacokinetic data from a single‐arm, open‐label, phase 2/3 pediatric clinical trial of 53 pediatric patients at least 28 days of age and weighing at least 3 kg with confirmed severe acute respiratory syndrome coronavirus 2 infection and mild, moderate, or severe COVID‐19. At the time of the April 25, 2022, approval action, the US Food and Drug Administration also revoked the emergency use authorization for RDV that previously covered this pediatric population. This article summarizes key issues and regulatory considerations involved in the RDV COVID‐19 pediatric development program, including the evolution of the emergency use authorization issued for RDV as results from registrational studies became available, and discusses lessons learned.
Functionalized reduced graphene oxide as a useful and efficient base catalyst for the preparation of 4H‐pyran and pyran‐like tacrine compounds and their antibacterial activity
Authors: Mirza‐Aghayan Maryam , Mohammadi Marzieh , Boukherroub Rabah , Ravanavard Katayoon 
Published: September 2022

AbstractAn easy, effective and eco‐friendly one‐pot process for the preparation of 4H‐pyran compounds has been established by using a catalytic amount of reduced graphene oxide functionalized with diethylenetriamine (rGO‐DETA) in water under mild conditions. The functionalized catalyst was very effective for this one‐pot reaction and provided the desired products 1a–t with good to high yields (87%–97%) in short reaction times. Moreover, rGO‐DETA composite could be reused for four cycles without an obvious decrease in its performance. In the next step, two pyran derivatives 1f and 1h were used to synthesize the corresponding pyran‐like tacrine derivatives 3f and 3h via the reaction of cyclohexanone, aluminum trichloride in reflux of 1,2‐dichloroethane as solvent. Antibacterial activity of several of the prepared compounds was assessed against Gram‐positive and Gram‐negative bacteria by well and disk diffusion techniques. The 4H‐pyran 1g and 1s (2000 μg/ml) were effective against Micrococcus luteus as a Gram‐positive bacterium by recording a zone of inhibition of 15 and 16 mm, respectively. 4H‐pyran 1m showed moderate antibacterial behavior against both M. luteus and Serratia marcescens. Pyran‐like tacrine analog 3f (50 mg/ml) displayed antibacterial behavior towards Staphylococcus aureus as Gram‐positive and S. marcescens as Gram‐negative bacteria with zones of inhibition of 13 and 12 mm, respectively. 4H‐pyran 1j featured a minimum inhibitory concentration value of 39.06 μg/ml for M. luteus, which is the closest value to ampicillin.
Shock and kill within the CNS: A promising HIV eradication approach?
Authors: Nühn Marieke M , Gumbs Stephanie B H , Buchholtz Ninée V E J , Jannink Lisanne M , Gharu Lavina , de Witte Lot D , Wensing Annemarie M J , Lewin Sharon R , Nijhuis Monique , Symons Jori 
Published: September 2022

AbstractThe most studied HIV eradication approach is the “shock and kill” strategy, which aims to reactivate the latent reservoir by latency reversing agents (LRAs) and allowing elimination of these cells by immune-mediated clearance or viral cytopathic effects. The CNS is an anatomic compartment in which (persistent) HIV plays an important role in HIV-associated neurocognitive disorder. Restriction of the CNS by the blood–brain barrier is important for maintenance of homeostasis of the CNS microenvironment, which includes CNS-specific cell types, expression of transcription factors, and altered immune surveillance. Within the CNS predominantly myeloid cells such as microglia and perivascular macrophages are thought to be a reservoir of persistent HIV infection. Nevertheless, infection of T cells and astrocytes might also impact HIV infection in the CNS. Genetic adaptation to this microenvironment results in genetically distinct, compartmentalized viral populations with differences in transcription profiles. Because of these differences in transcription profiles, LRAs might have different effects within the CNS as compared with the periphery. Moreover, reactivation of HIV in the brain and elimination of cells within the CNS might be complex and could have detrimental consequences. Finally, independent of activity on latent HIV, LRAs themselves can have adverse neurologic effects. We provide an extensive overview of the current knowledge on compartmentalized (persistent) HIV infection in the CNS and on the “shock and kill” strategy. Subsequently, we reflect on the impact and promise of the “shock and kill” strategy on the elimination of persistent HIV in the CNS.
Emergency pharmacology for the CT technologist
Authors: Currie Geoffrey M. 
Published: September 2022

AbstractThe scope of practice of the medical radiation practitioner demands knowledge and understanding of the indications, contraindications, warnings, precautions, proper use, drug interactions and adverse reactions of a variety of medications. The risk of patient deterioration or acute emergent event, particularly following contrast administration, makes the command of crash cart medications particularly important. This article explores the pharmacological principles of medications most likely to be required in a medical emergency in the medical radiation department and in particular by the computed tomography (CT) technologist. The article also outlines early warning signs to assist in identifying the emergent or deteriorating patient. The learning outlined is designed to equip medical radiation practitioners with the capacity to identify and respond to a medical emergency typical of the medical radiation department, and to respond to that situation with the appropriate use of emergency medications where appropriate. The ability of medical radiation practitioners to recognise and respond to (including the use of medicines) the deteriorating patient or circumstances of a medically urgent nature are key capabilities required to meet minimum standards for Medical Radiation Practice Board of Australia registration and National Safety and Quality Health Service standards.
Quantifying perceptual resolution for autostereoscopic three‐dimensional displays
Authors: Cheng Mengyi , Zhong Jing , Wang Yiyao , Li Jijing , Yuan Jin , He Jieyong , Wang Jiahui , Liang Haowen , Zhou Jianying 
Published: September 2022

AbstractThe perceptual experience issue is particularly important for autostereoscopic three‐dimensional (3D) displays since the perceptual resolution has a great correlation between panel resolution and other 3D display performances, but normally used effective resolution only considers the amount of information being sent to a certain viewing point. This work describes that the visual factors should be taken into consideration associated with resolution and contrast simultaneously to evaluate perceptual 3D resolution. We propose a quantitative evaluation of perceptual resolution of 3D displays from modulated contrast based on the contrast sensitivity function (CSF). A switchable parallax‐barrier display and a directional backlight display providing glasses‐free autostereoscopic vision are experimentally studied to verify the validity of the characterization. Due to the nonlinear response of the CSF threshold curve, less than 50% of the panel resolution in parallax‐barrier 3D displays is perceived, while the display with directional backlight illumination is shown to retain the panel resolution for perceptual experience as expected. We foresee that this study provides a practically objective paradigm to characterize the subjective perceptual resolution and the presented perceptual resolution can be served as a design guideline to achieve an improved 3D viewing experience.
Utilization of magnetic pomelo peel‐derived biochar for extraction and liquid chromatography‐mass spectrometry determination of opioid drugs in wastewaters
Authors: Zhang Suling , Hua Ziluo , Yao Weixuan , Lü Ting , Zhang Dong , Zhao Hongting 
Published: September 2022

In this study, magnetic pomelo peel‐derived biochar composite was fabricated and applied as a low‐cost adsorbent for the simultaneous extraction of morphine‐like opioids named morphine, codeine, and 6‐monoacetylmorphine from wastewaters, prior to their determination via liquid chromatography‐mass spectrometry. A total of four biochar products were synthesized under different pyrolytic temperatures of 400, 500, 600, and 700°C, respectively, and the 400°C biochar was found to have the greatest extraction ability, with enrichment factors of 34, 58, and 61 for the three drugs. The primary adsorption mechanism includes π‐π interaction and H‐bonding. Parameters affecting the extraction of opioids were optimized. Under optimum conditions (such as pH = 7; adsorbent amount = 15 mg; sample volume = 20 ml; eluent solvent, 200 µl of methanol), the method was proved to be linear in the range of 0.05–10.0 µg/L, with coefficients of determination greater than 0.99, and the limits of detection were 0.006–0.010 µg/L. In‐batch and inter‐batch precisions were 1.8%–6.5% and 4.8%–10.6%, respectively. The method was successfully applied to the determination of the target opioids in the samples of influent and effluent wastewater. The developed method by using magnetic pomelo peel‐derived biochar could potentially be applied for the effective estimation of illicit drug consumption.
The policy responses of tourism agencies to emerging digital skills constraints: A critical assessment of six countries
Authors: Parsons David , Choi Miju , Thomas Rhodri , Glyptou Kyriaki , Walsh Kenneth 
Published: September 2022

AbstractThis paper analyses policies and practices designed to support digital transformation in the tourism workforce in six OECD countries, namely Germany, Greece, Iceland, New Zealand, Switzerland, and the United Kingdom. Data for the project were gathered via a questionnaire survey, interviews with key informants and examination of various policy documents in 2021. Contrasting practice in relation to digital skills development is revealed. Significant deficiencies are evident in relation to the availability of high‐quality data, evaluation, understanding, leadership, and infrastructure among the six countries. Ways in which effective policy development might emerge are suggested.
Long non‐coding RNA MALAT1 promotes Th2 differentiation by regulating microRNA‐135b‐5p/GATA‐3 axis in children with allergic rhinitis
Authors: Wu Xiong‐Hui , Zhao Si‐Jun , Huang Wei‐Qing , Huang Li‐Hua , Luo Xin‐You , Long Song‐Liang 
Published: September 2022

AbstractAllergic rhinitis (AR) threatens patient survival. CD4+ T cells play key roles in AR progression. Long non‐coding RNAs (lncRNAs) are key regulators of cell differentiation. Therefore, we investigated the molecular mechanism of the lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in AR. Expression levels of MALAT1, microRNA (miR)‐135b‐5p, interleukin‐4 (IL‐4), and GATA‐binding protein 3 (GATA‐3) in the nasal mucosa of AR patients were quantified. CD4+ T cells were isolated from the peripheral blood of healthy volunteers and treated with ovalbumin (OVA) and Th2 inducers. After MALAT1 and miR‐135b‐5p levels changed in CD4+ T cells, the proportion of IL‐4‐expressing cells and the levels of IL‐4 and GATA‐3 in OVA‐induced CD4+ T cells were determined. Binding relationships among MALAT1, miR‐135b‐5p, and GATA‐3 were predicted and verified. Rescue experiments were performed to confirm the role of the MALAT1/miR‐135b‐5p/GATA‐3 axis in Th2 differentiation of CD4+ T cells. MALAT1, IL‐4, and GATA‐3 expression was upregulated, whereas miR‐135b‐5p expression was downregulated, in patients with AR. MALAT1 knockdown or miR‐135b‐5p overexpression in CD4+ T cells notably decreased the proportion of IL‐4‐expressing cells and downregulated GATA‐3 and IL‐4 expression in OVA‐induced CD4+ T cells. MALAT1 and GATA‐3 exhibited competitive binding toward miR‐135b‐5p. MALAT1 facilitated CD4+ T cell Th2 differentiation via the miR‐135b‐5p/GATA‐3 axis. MALAT1 facilitated AR development by facilitating CD4+ T cell Th2 differentiation via the miR‐135b‐5p/GATA‐3 axis. This study may provide guidance for clinical treatment of AR.
Phantosmia May Predict Long‐Term Measurable Olfactory Dysfunction After COVID‐19
Authors: Leung Jai‐Sen , Cordano Valentina Paz , Fuentes‐López Eduardo , Lagos Antonia Elisa , García‐Huidobro Francisco Gustavo , Aliaga Rodrigo , Díaz Luis Antonio , García‐Salum Tamara , Salinas Erick , Toro Adriana , Callejas Claudio Andrés , Riquelme Arnoldo , Palmer James N. , Medina Rafael A. , González G Claudia 
Published: September 2022

ObjectivesPersistent olfactory dysfunction (OD) after 6 months caused by SARS‐CoV‐2 infection has been reported with a variable prevalence worldwide. This study aimed to determine the prevalence of long‐term OD and identify predisposing factors.MethodsA prospective cohort study was conducted on 100 adults with COVID‐19. Olfactory function was assessed with the University of Pennsylvania Smell Identification Test and a symptom survey at the onset of disease and 30 days later. Patients with persistent quantitative OD at the second assessment were reevaluated after 1 year. Demographic variables, symptoms, and the degree of smell loss were analyzed.ResultsParticipants included 100 patients. The mean age was 42.2 ± 15.6 years, 55 (55%) were female, and 56 (56%) were outpatients. Baseline smell loss was identified in 75/100 (75%) patients, decreasing to 39/95 (40%) after 1 month, and persisting in 29 patients after 1 year. Phantosmia at baseline was the only risk factor identified for persistent OD after 1 year (relative risk 2.51; 95% confidence interval 1.53–4.12; p < 0.001). Regardless of the outcome in smell function, a significant decline in olfaction was associated with the presence of phantosmia at 1 month (β = −12.39; 95% CI −19.82 to −4.95; p < 0.01).ConclusionsSARS‐CoV‐2 (2019–2020 variants) produced a highly frequent OD that persisted in 29% of the patients after 1 year. The presence of phantosmia at baseline and 1 month was associated with a worse evolution, but phantosmia may interfere with the performance in an identification smell test. A longer follow‐up is required in these patients.Level of Evidence2 Laryngoscope, 132:2445–2452, 2022
Enhanced Photovoltaic Performance of Benzothiadiazole‐Based Polymers by Controlling their Backbone Planarity for Organic Solar Cells
Authors: Tamilavan Vellaiappillai , Kim Danbi , Yang Hyun‐Seock , Shin Insoo , Kim Junghwan , Lee Bo Ram , Park Sung Heum 
Published: September 2022

AbstractHere, a new synthetic strategy for converting low‐energy benzo[c][1,2,5]thiadiazole (BT)‐based polymers into efficient polymeric donors for non‐fullerene acceptor‐based organic solar cells (NFA–OSCs) is demonstrated. A highly planar 5,6‐difluoro‐benzo[c][1,2,5]thiadiazole (ffBT)‐based alternating polymer, P1, comprising of electron‐rich 4,8‐bis(5‐(2‐ethylhexyl)thiophen‐2‐yl)benzo[1,2‐b:4,5‐b']dithiophene (BDTT) and strong electron‐deficient 5,6‐difluoro‐4,7‐bis(4‐octylthiophen‐2‐yl)benzo[c][1,2,5]thiadiazole (DTffBT) units is prepared. Additionally, two ternary polymers, P2 and P3, are preparedby replacing 25% and 50% of the DTffBT unit on the P1 backbone with a weak electron‐deficient 2,5‐dioctyl‐4,6‐di(thiophen‐2‐yl)pyrrolo[3,4‐c]pyrrole‐1,3(2H,5H)‐dione (DTPPD) unit, which has a twisted but well‐controlled wavy backbone. The properties of the resulting polymers, P1–P3, are investigated to understand the effects of changing the planarity and curvature of the backbone of the BT‐based polymers. Notably, increasing the concentration of the DTPPD unit on P1 results in ablue‐shift in absorption band and relatively deep energy levels. Further, the π–π stacking of the polymers is decreased by increasing the amount of DTPPD units on P1. The NFA–OSCs fabricated using P1–P3 as the electron donor afford maximum power conversion efficiencies (PCE) of 2.46%, 4.52%, and 7.54%, respectively. Overall, the photovoltaic performance of the BT‐based polymers is significantly improved by lowering their planarity and/or changing their backbone curvature.
Multiplication in vector‐valued anisotropic function spaces and applications to non‐linear partial differential equations
Authors: Köhne Matthias , Saal Jürgen 
Published: September 2022

AbstractWe study multiplication as well as Nemytskij operators in anisotropic vector‐valued Besov spaces , Bessel potential spaces , and Sobolev–Slobodeckij spaces . Concerning multiplication we obtain optimal estimates, which constitute generalizations and improvements of known estimates in the isotropic/scalar‐valued case. Concerning Nemytskij operators we consider the acting of analytic functions on supercritial anisotropic vector‐valued function spaces of the above type. Moreover, we show how the given estimates may be used in order to improve results on quasilinear evolution equations as well as their proofs.
The influence of language style (formal vs. colloquial) on the effectiveness of charitable appeals
Authors: Pfeiffer Bruce E. , Sundar Aparna , Cao Edita 
Published: September 2022

AbstractThis paper investigates the influence of language style (formal vs. colloquial) on the effectiveness of charitable appeals. Although prior research has found persuasive effects associated with colloquial language style, we propose that the influence of language style is context dependent. Charitable appeals generally address relatively serious topics. Since formal language style is more context congruent in communicating this seriousness, it should be more effective in expressing the emotional arousal or the effort of the communicator, which we expected to result in greater charitable support. Across four studies, we provide important insights on how charitable organizations can better align language style to increase donor support. We find that formal language style (vs. colloquial) results in greater charitable support. We also find evidence for the underlying role of perceptions of emotional arousal, as in indication of effort, in this relationship. Lastly, we find support for a moderator related to one's prior beliefs. Since individuals with high just‐world beliefs are motivated to vary their prosocial behaviors, we find a moderating effect of just‐world beliefs, but only when the belief is high, that is, when individuals seek accountability.
Advances in mass spectrometry imaging for toxicological analysis and safety evaluation of pharmaceuticals
Authors: Chen Yilin , Xie Yanqiao , Li Linnan , Wang Zhengtao , Yang Li 
Published: September 2022

AbstractSafety issues caused by pharmaceuticals have frequently occurred worldwide, posing a tremendous threat to human health. As an essential part of drug development, the toxicological analysis and safety evaluation is of great significance. In addition, the risk of pharmaceuticals accumulation in the environment and the monitoring of the toxicity from natural medicines have also received ongoing concerns. Due to a lack of spatial distribution information provided by common analytical methods, analyses that provide spatial dimensions could serve as complementary safety evaluation methods for better prediction and evaluation of drug toxicity. With advances in technical solutions and software algorithms, mass spectrometry imaging (MSI) has received increasing attention as a popular analytical tool that enables the simultaneous implementation of qualitative, quantitative, and localization without complex sample pretreatment and labeling steps. In recent years, MSI has become more attractive, powerful, and sensitive and has been applied in several scientific fields that can meet the safety assessment requirements. This review aims to cover a detailed summary of the various MSI technologies utilized in the biomedical and pharmaceutical area, including technical principles, advantages, current status, and future trends. Representative applications and developments in the safety‐related issues of different pharmaceuticals and natural medicines are also described to provide a reference for pharmaceutical research, improve rational clinical medicine use, and ensure public safety.
Defects in DNA double‐strand break repair resensitize antibiotic‐resistant Escherichia coli to multiple bactericidal antibiotics
Authors: Revitt‐Mills Sarah A. , Wright Elizabeth K. , Vereker Madaline , O'Flaherty Callum , McPherson Fairley , Dawson Catherine , van Oijen Antoine M. , Robinson Andrew 
Published: September 2022

AbstractAntibiotic resistance is becoming increasingly prevalent amongst bacterial pathogens and there is an urgent need to develop new types of antibiotics with novel modes of action. One promising strategy is to develop resistance‐breaker compounds, which inhibit resistance mechanisms and thus resensitize bacteria to existing antibiotics. In the current study, we identify bacterial DNA double‐strand break repair as a promising target for the development of resistance‐breaking co‐therapies. We examined genetic variants of Escherichia coli that combined antibiotic‐resistance determinants with DNA repair defects. We observed that defects in the double‐strand break repair pathway led to significant resensitization toward five bactericidal antibiotics representing different functional classes. Effects ranged from partial to full resensitization. For ciprofloxacin and nitrofurantoin, sensitization manifested as a reduction in the minimum inhibitory concentration. For kanamycin and trimethoprim, sensitivity manifested through increased rates of killing at high antibiotic concentrations. For ampicillin, repair defects dramatically reduced antibiotic tolerance. Ciprofloxacin, nitrofurantoin, and trimethoprim induce the promutagenic SOS response. Disruption of double‐strand break repair strongly dampened the induction of SOS by these antibiotics. Our findings suggest that if break‐repair inhibitors can be developed they could resensitize antibiotic‐resistant bacteria to multiple classes of existing antibiotics and may suppress the development of de novo antibiotic‐resistance mutations.