bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atezolizumab and bevacizumab combination compared with sorafenib as the first‐line systemic treatment for patients with unresectable hepatocellular carcinoma: A cost‐effectiveness analysis in China and the United states
Authors: Wen Feng , Zheng Hanrui , Zhang Pengfei , Liao Weiting , Zhou Kexun , Li Qiu 
Published: February 2021

AbstractBackground & AimsIn patients with unresectable hepatocellular carcinoma (HCC), the combination of atezolizumab and bevacizumab improved progression‐free survival (PFS) and overall survival compared with sorafenib in the IMbrave150 trial. However, whether the price of the combination could be affordable is unknown. The current study assessed the cost‐effectiveness of the combination of atezolizumab and bevacizumab as first‐line systemic therapy for patients with unresectable HCC from the Chinese and American payers' perspective.MethodsA Markov model was built based on a global, multicentre, open‐label, phase III randomized trial (IMbrave150, NCT03434379) that included three states of the patient's health: stable disease (SD), progressive disease (PD) and death. Data for all medical costs were acquired from the Red Book, published literature and West China Hospital. Quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratios (ICERs) were the primary outcomes. Sensitivity analyses were performed to evaluate the model uncertainty.ResultsThe treatment consisting of a combination of atezolizumab and bevacizumab yielded an additional 0.53 QALYs compared with sorafenib alone, leading to an ICER of $145,546.21 per QALY in China and $168,030.21 per QALY in the USA, both beyond the willing‐to‐pay threshold ($28,527.00/QALY in China and $150,000.00 /QALY in the USA). The utility of the PD state was the most influential factor in the Chinese model, and the American model was the most sensitive to the price of sorafenib. The results of the models were robust across sensitivity analyses.ConclusionThe combination of atezolizumab and bevacizumab was not a cost‐effective strategy for the first‐line systemic treatment of unresectable HCC from the Chinese and American payers' perspective.
VviNAC33 promotes organ de‐greening and represses vegetative growth during the vegetative‐to‐mature phase transition in grapevine
Authors: D’Incà Erica , Cazzaniga Stefano , Foresti Chiara , Vitulo Nicola , Bertini Edoardo , Galli Mary , Gallavotti Andrea , Pezzotti Mario , Battista Tornielli Giovanni , Zenoni Sara 
Published: February 2021

Summary

Plants undergo several developmental transitions during their life cycle. In grapevine, a perennial woody fruit crop, the transition from vegetative/green‐to‐mature/woody growth involves transcriptomic reprogramming orchestrated by a small group of genes encoding regulators, but the underlying molecular mechanisms are not fully understood.

We investigated the function of the transcriptional regulator VviNAC33 by generating and characterizing transgenic overexpressing grapevine lines and a chimeric repressor, and by exploring its putative targets through a DNA affinity purification sequencing (DAP‐seq) approach combined with transcriptomic data.

We demonstrated that VviNAC33 induces leaf de‐greening, inhibits organ growth and directly activates the expression of STAY‐GREEN PROTEIN 1 (SGR1), which is involved in Chl and photosystem degradation, and AUTOPHAGY 8f (ATG8f), which is involved in the maturation of autophagosomes. Furthermore, we show that VviNAC33 directly inhibits AUXIN EFFLUX FACILITATOR PIN1, RopGEF1 and ATP SYNTHASE GAMMA CHAIN 1T (ATPC1), which are involved in photosystem II integrity and activity.

Our results show that VviNAC33 plays a major role in terminating photosynthetic activity and organ growth as part of a regulatory network governing the vegetative‐to‐mature phase transition.
Transesophageal three‐dimensional echocardiographic guidance for pacemaker lead extraction
Authors: Burkett Dale A. , Runciman Martin , Jone Pei‐Ni , Collins Kathryn K. 
Published: February 2021

AbstractBackgroundThe ability of transesophageal three‐dimensional echocardiography (3DE) to aid in pacemaker lead extraction has not yet been evaluated. 3DE provides real‐time evaluation of intracardiac anatomy and the location of pacemaker leads in greater detail than either fluoroscopy or –two‐dimensional echocardiography (2DE), aiding in the extraction of such leads, which can be potentially dangerous. We sought to investigate the feasibility and utility of 3DE to visualize intracardiac anatomy and pacemaker leads, and to assist in lead extraction procedures.MethodsWe utilized 3DE in nine encounters for eight different patients, to visualize intracardiac anatomy and leads before, during, and after extraction to evaluate the feasibility and utility to aid in the procedure and evaluate for potential sequelae.Results3DE was able to identify pertinent intracardiac anatomy and leads in all cases. 3DE detected procedural complications or altered management in five of nine encounters (five of eight patients); this included detection of an avulsed papillary muscle, tricuspid valve leaflet damage, and cast/thrombus after lead removal, as well as adjustment of excess lead slack to avoid future valve damage, or risk stratification of lead removal.Conclusion3DE is feasible and adds utility to lead extraction cases by visualizing intracardiac anatomy and leads beyond fluoroscopy or 2DE, providing real‐time information during extraction, and identifying potential complications.
On the nonpathological nature of ST‐segment elevation in lateral leads in patients with CRBBB
Authors: Madias John E. 
Published: February 2021

AbstractStable ST‐segment elevation (STSE) in the lateral electrocardiogram (ECG) leads (i.e., I, II, aVL, V5, and V6) are frequently encountered in association with stable and transient complete right bundle branch block (CRBBB). These STSE in the lateral ECG leads in patients with CRBBB, represent parallel changes to the ST‐segment depression seen in the V1‐V3 leads, and both represent secondary ECG changes expected in patients with intraventricular conduction delays, and they are opposite in polarity to the latter part of the QRS complexes. Proprietary automated ECG interpretation algorithms provided by the different electrocardiographs associate such ECG changes in the lateral leads in the presence of CBBB to “lateral myocardial infarction, ischemia, or injury,” “pericarditis,” or “early repolarization,” which results in inappropriate concern among clinicians, and leads to costly unnecessary diagnostic testing. This piece strives to reassure clinicians about the nonpathological nature of lateral STSE in ECGs with CRBBB.
Integrated associations of nasopharyngeal and serum metabolome with bronchiolitis severity and asthma: A multicenter prospective cohort study
Authors: Fujiogi Michimasa , Camargo Carlos A. , Raita Yoshihiko , Zhu Zhaozhong , Celedón Juan C. , Mansbach Jonathan M. , Spergel Jonathan M. , Hasegawa Kohei 
Published: February 2021

AbstractBackgroundWhile infant bronchiolitis contributes to substantial acute (eg, severity) and chronic (eg, asthma development) morbidities, its pathobiology remains uncertain. We examined the integrated relationships of local (nasopharyngeal) and systemic (serum) responses with bronchiolitis morbidities.MethodsIn a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we applied a network analysis approach to identify distinct networks (modules)—clusters of densely interconnected metabolites—of the nasopharyngeal and serum metabolome. We examined their individual and integrated relationships with acute severity (defined by positive pressure ventilation [PPV] use) and asthma development by age 5 years.ResultsIn 140 infants, we identified 285 nasopharyngeal and 639 serum metabolites. Network analysis revealed 7 nasopharyngeal and 8 serum modules. At the individual module level, nasopharyngeal‐amino acid, tricarboxylic acid (TCA) cycle, and carnitine modules were associated with higher risk of PPV use (r > .20; P < .001), while serum‐carnitine, amino acid, and glycerophosphorylcholine (GPC)/glycerophosphorylethanolamine (GPE) modules were associated with lower risk (all r < −.20; P < .05). The integrated analysis for PPV use revealed consistent findings—for example, nasopharyngeal‐TCA (adjOR: 2.87, 95% CI: 1.68‐12.2) and serum‐GPC/GPE (adjOR: 0.54, 95% CI: 0.38‐0.80) modules—and an additional module—serum‐glucose‐alanine cycle module (adjOR: 0.69, 95% CI: 0.56‐0.86). With asthma risk, there were no individual associations, but there were integrated associations (eg, nasopharyngeal‐carnitine module; adjOR: 1.48, 95% CI: 1.11‐1.99).ConclusionIn infants with bronchiolitis, we found integrated relationships of local and systemic metabolome networks with acute and chronic morbidity. Our findings advance research into the complex interplay among respiratory viruses, local and systemic response, and disease pathobiology in infants with bronchiolitis.
Variation of PHT families adapts salt cress to phosphate limitation under salinity
Authors: Lv Sulian , Wang Duoliya , Jiang Ping , Jia Weitao , Li Yinxin 
Published: February 2021

AbstractSalt cress (Eutrema salsugineum) presents relatively high phosphate (Pi) use efficiency cy in its natural habitat. Phosphate Transporters (PHTs) play critical roles in Pi acquisition and homeostasis. Here, a comparative study of PHT families between salt cress and Arabidopsis was performed. A total of 27 putative PHT genes were identified in E. salsugineum genome. Notably, seven tandem genes encoding PHT1;3 were found, and function analysis in Arabidopsis indicated at least six EsPHT1;3s participated in Pi uptake. Meanwhile, different expression profiles of PHT genes between the two species under Pi limitation and salt stress were documented. Most PHT1 genes were down‐regulated in Arabidopsis while up‐regulated in salt cress under salinity, among which EsPHT1;9 was further characterized. EsPHT1;9 was involved in root‐to‐shoot Pi translocation. Particularly, the promoter of EsPHT1;9 outperformed that of AtPHT1;9 in promoting Pi translocation, K+/Na+ ratio, thereby salt tolerance. Through cis‐element analysis, we identified a bZIP transcription factor EsABF5 negatively regulating EsPHT1;9 and plant tolerance to low‐Pi and salt stress. Altogether, more copies and divergent transcriptional regulation of PHT genes contribute to salt cress adaptation to the co‐occurrence of salinity and Pi limitation, which add our knowledge on the evolutionary and molecular component of multistress‐ tolerance of this species.
Fine‐Feature Modifications to Strained Ruthenium Complexes Radically Alter Their Hypoxic Anticancer Activity†
Authors: Cole Houston D. , Roque John A. , Lifshits Liubov M. , Hodges Rachel , Barrett Patrick C. , Havrylyuk Dmytro , Heidary David , Ramasamy Elamparuthi , Cameron Colin G. , Glazer Edith C. , McFarland Sherri A. 
Published: February 2021

AbstractIn an earlier study of π‐expansive ruthenium complexes for photodynamic and photochemo‐therapies, it was shown that a pair of structural isomers differing only in the connection point of a naphthalene residue exhibited vastly different biological activity. These isomers are further explored in this paper through the activity of their functionalized derivatives. In normoxia, the inactive 2‐NIP isomer (5) can be made as photocytotoxic as the active 1‐NIP isomer (1) by functionalizing with methyl or methoxy groups, while methoxy variants of the 1‐NIP isomer became inactive. In all cases, the singlet oxygen sensitization quantum yield was below 1%. Hypoxic photocytotoxicity was attenuated, with only three of the series showing any activity, notwithstanding the photodissociative ligands. The results here are consistent with the earlier findings in that seemingly minor structural modifications on the non‐strained ligand can dramatically modulate the normoxic and hypoxic activity of these strained compounds and that these changes appear to exert a greater influence on photocytotoxicity than singlet oxygen sensitization or rates of photosubstitution in cell‐free conditions would suggest.
Comprehensive diversity assessment of walnut‐associated xanthomonads reveal the occurrence of distinct Xanthomonas arboricola lineages and of a new species (Xanthomonas euroxanthea) within the same tree
Authors: Fernandes Camila , Albuquerque Pedro , Mariz‐Ponte Nuno , Cruz Leonor , Tavares Fernando 
Published: February 2021

AbstractXanthomonas arboricola pv. juglandis (Xaj) is the aetiological agent of walnut diseases causing economic losses on walnut production worldwide. This phytopathogen is spread around the world where walnuts are produced and has a considerable genetic diversity. Using a comprehensive sampling methodology, focusing on factors that could influence the diversity of walnut‐colonizing Xaj in Portugal, this work provides new insights on xanthomonad populations on walnut. Genetic diversity was assessed by multilocus sequence analysis (MLSA) and dot blot hybridization patterns on 131 Xanthomonas isolates obtained from 64 walnut trees considering epidemiological metadata such as year of isolation, distinct bioclimatic regions, production regimes, and host‐related features. The results showed that the majority of isolates were split into 17 lineages of Xaj, while the other isolates clustered in four MLSA groups that did not include Xaj strains. These four groups were represented by three lineages of X. arboricola, and 11 lineages of Xanthomonas spp., including strains assigned to the recently proposed new species Xanthomonas euroxanthea. Furthermore, distinct Xaj, X. arboricola, and Xanthomonas spp. were isolated from the same walnut tree, suggesting possible genetic admixture within the same host. Phylogenetic analysis through geoBurst revealed the high diversity of these Xanthomonas spp. populations. Assessment of type III effector genes gave the indication that some Xanthomonas spp. strains were nonpathogenic on walnut, with the exception for X. euroxanthea CPBF 424. Altogether, these findings add to the thorough characterization of walnut‐associated xanthomonads in Portugal, providing a comprehensive snapshot of the current diversity that could contribute to risk assessment analysis and improve phytosanitary control.
What's In It For Us? Benevolence, National Security, and Digital Surveillance
Authors: Degli Esposti Sara , Ball Kirstie , Dibb Sally 
Published: February 2021

AbstractThis article challenges suggestions that citizens should accept digital surveillance technologies (DSTs) and trade their privacy for better security. Drawing on data from nine EU countries, this research shows that citizens’ support for DSTs varies not only depending on the way their data are used but also depending on their views of the security agency operating them. Using an institutional trustworthiness lens, this research investigates three DST cases—smart CCTV, smartphone location tracking, and deep packet inspection—that present escalating degrees of privacy risk to citizens. The findings show that the perceived benevolence of security agencies is essential to acceptability in all three cases. For DSTs with greater privacy risk, questions of competence and integrity enter citizens' assessments.
Levels of education and technical skills in registered nurses working in post‐anaesthesia care units in Sweden
Authors: Dahlberg Karuna , Jaensson Maria , Flodberg Magnus , Månsson Sandra , Nilsson Ulrica 
Published: February 2021

AbstractBackgroundSpecialized nursing care should be provided by nurses working in post‐anaesthesia care units to ensure safe and successful recovery after surgery and anaesthesia. However, there is no consensus regarding the competence and education needed by nurses working in post‐anaesthesia care units.AimThe aim of this study is to describe and compare levels of education and technical skills in registered nurses working in post‐anaesthesia care units in Sweden, as well as the education that post‐anaesthesia care unit nurse managers’ desire for registered nurses working in post‐anaesthesia care units.MethodsThis descriptive cross‐sectional study was conducted in Sweden between September and December of 2019. A web‐based survey was developed that included questions about the levels of education and technical skills possessed by registered nurses working in Swedish post‐anaesthesia care units and desired by nurse managers for these nurses. The survey was evaluated for content validity by four experts. The survey was distributed to the nurse manager of each studied post‐anaesthesia care unit. All nurse managers received written information and were informed that submitting the survey was considered as consenting to participate in the study.ResultsMost surveyed nurses held a postgraduate diploma in specialist nursing. Registered nurses performed many tasks autonomously; however, there was a significant difference between specialist nurses and registered nurses, with specialist nurses being more autonomous than registered nurses. Most of the nurse managers (n = 31/45) wanted the registered nurses in their units to have education in postoperative care. The relatively low overall response rate of 58% is a study limitation.ConclusionsRegistered nurses working in post‐anaesthesia care units in Sweden must have various technical skills. Some of these skills are only performed by specialist nurses, indicating that postoperative care is an advanced level of nursing care.
Distinct macrophage phenotypes and redox environment during the fin fold regenerative process in zebrafish
Authors: Paredes Lais Cavalieri , Luz Rebeca Bosso dos Santos , Tozzi Ollavo Nogueira , de Carvalho Lucicleide Ângelo Silva Jungles , Calado Sabrina Loise de Morais , Padovani Bárbara Nunes , Fénero Camila Idelí Morales , do Amaral Mariana Abrantes , de Assis Helena Cristina da Silva , Câmara Niels Olsen Saraiva , Braga Tarcio Teodoro 
Published: February 2021

AbstractIn contrast to mammals, zebrafish (Danio rerio) has the ability to regenerate injured sites such as different tissues present in the fin. It is known that cells of the innate immune system play essential roles in regeneration; however, some aspects of the molecular mechanisms by which these cells orchestrate regeneration remain unknown. This study aimed to evaluate the infiltration dynamics of neutrophils and macrophages in the regenerative process of fin fold in regard to the influence of the redox environment and oxidative pathways. Fin fold amputation was performed on transgenic larvae for macrophage‐expressed gene 1 (mpeg1), lysozyme (lyz), myeloperoxidase (mpo) and tumour necrosis factor alpha (TNFα) at 3 days post‐fertilization, followed by confocal microscopy imaging and measurement of the activities of oxidant and antioxidant enzymes. We observed initially an increase in the number of neutrophils (lyz:DsRed+/mpx:GFP+) and then macrophages (mpeg1+) in the injury site followed by a decrease in neutrophils at 7 days post‐amputation (dpa). Moreover, macrophages switch from a pro‐inflammatory to an anti‐inflammatory profile throughout the process, while the activity of superoxide dismutase (SOD) increased at 1 dpa and catalase (CAT) at 5 dpa. Higher levels of lipid peroxidation were also detected during regeneration. Despite oxidative stress, there is, therefore, an antioxidant response throughout the regeneration of the caudal fin. The present work can contribute to future studies on the development of cell therapies, achieving greater effectiveness in the treatment of diseases related to the formation of fibrotic tissue.
Can the G20 serve as a launchpad for a multilateral investment agreement?
Authors: Berger Axel , Liu Wan‐Hsin 
Published: February 2021

AbstractThe international system for the governance of foreign investments is highly fragmented consisting mainly of bilateral agreements. With the adoption of nine guiding principles for global investment policy‐making in 2016, some observers argue that the G20 can actually serve as a launchpad for negotiations of a multilateral investment agreement. This paper provides empirical evidence on the question of whether the contents of international investment agreements (IIAs) have gradually converged to facilitate the multilateralisation of investment rules. We find that IIAs negotiated among non‐G20 countries are more similar to each other than those concluded by G20 countries in general and even more so since 2000 in particular. This result calls into question the premise that the G20 can serve as the most suitable forum to initiate multilateral negotiations on multilateral investment rules. Instead, an extended analysis using different country grouping criteria suggests that the Member States of the European Union may be a more suitable alternative in this regard. Here, the EU can jointly take a leading role in facilitating related negotiations on multilateral investment rules.
Assessing the uncertainty of treatment outcomes in a previous systematic review of venous leg ulcer randomized controlled trials: Additional secondary analysis
Authors: Eckert Kristen A. , Carter Marissa J. 
Published: February 2021

AbstractIn this secondary analysis of a previous systematic review, we assessed randomized controlled trials evaluating treatments of venous leg ulcers in terms of factors that affect risk of bias at the study level and thus uncertainty of outcomes obtained from the interventions. Articles that assessed the wound bed condition in venous leg ulcers and that were published in English between 1998 and May 22, 2018 were previously searched in PubMed, Embase, CINAHL, CENTRAL, Scopus, Science Direct, and Web of Science. Duplicates and retracted articles were excluded. The following data were extracted to assess the risk of bias: treatment groups; primary and secondary endpoints that were statistically tested between groups, including their results and p values; whether blinding of patients and assessors was done; whether allocation concealment was adequate; whether an intention‐to‐treat analysis was conducted; whether an appropriate power calculation was correctly done; and whether an appropriate multiplicity adjustment was made, as necessary. Pre‐ and post‐study power calculations were made. The step‐up Hochberg procedure adjusted for multiplicity. Results were analysed for all studies, pre‐2013 studies, and 2013/post‐2013 studies. We included 142 randomized controlled trials that evaluated 14,141 patients. Most studies lacked blinding (72.5–77.5%) and allocation concealment (88.7%). Only 49.3% of trials provided a power calculation, with 27.5% having an appropriate calculation correctly done. Adequate statistical power of the primary endpoint was found in 27.2% of trials. The lack of multiplicity adjustment in 98.6% of studies affected the uncertainty of outcomes in 20% of studies, with the majority of the secondary endpoints (67.7%) in those studies becoming non‐significant after multiplicity adjustment. Recent studies tended to weakly demonstrate improved certainty of outcomes. Venous leg ulcer randomized controlled trials have a high degree of uncertainty associated with treatment outcomes. Greater attention to trial design and conduct is needed to improve the evidence base.