bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental pressures on stomatal size may drive plant genome size evolution: evidence from a natural experiment with Cape geophytes
Authors: Veselý Pavel , Šmarda Petr , Bureš Petr , Stirton Charles , Muasya A Muthama , Mucina Ladislav , Horová Lucie , Veselá Kristýna , Šilerová Alexandra , Šmerda Jakub , Knápek Ondřej 
Published: May 2020

Abstract

Background and Aims
The idea that genome (size) evolution in eukaryotes could be driven by environmental factors is still vigorously debated. In extant plants, genome size correlates positively with stomatal size, leading to the idea that conditions enabling the existence of large stomata in fossil plants also supported growth of their genome size. We test this inductive assumption in drought-adapted, prostrate-leaved Cape (South Africa) geophytes where, compared with their upright-leaved geophytic ancestors, stomata develop in a favourably humid microclimate formed underneath their leaves.

Methods
Stomatal parameters (leaf cuticle imprints) and genome size (flow cytometry) were measured in 16 closely related geophytic species pairs from seven plant families. In each pair, representing a different genus, we contrasted a prostrate-leaved species with its upright-leaved phylogenetic relative, the latter whose stomata are exposed to the ambient arid climate.

Key Results
Except for one, all prostrate-leaves species had larger stomata, and in 13 of 16 pairs they also had larger genomes than their upright-leaved relatives. Stomatal density and theoretical maximum conductance were less in prostrate-leaved species with small guard cells (&lt;1 pL) but showed no systematic difference in species pairs with larger guard cells (&gt;1 pL). Giant stomata were observed in the prostrate-leaved Satyrium bicorne (89–137 µm long), despite its relatively small genome (2C = 9 Gbp).

Conclusions
Our results imply that climate, through selection on stomatal size, might be able to drive genome size evolution in plants. The data support the idea that plants from ‘greenhouse’ geological periods with large stomata might have generally had larger genome sizes when compared with extant plants, though this might not have been solely due to higher atmospheric CO2 in these periods but could also have been due to humid conditions prevailing at fossil deposit sites.
Ethical and Practical Issues Associated With the Possibility of Using Controlled Human Infection Trials in Developing a Hepatitis C Virus Vaccine
Authors: Cox Andrea , Sulkowski Mark , Sugarman Jeremy 
Published: May 2020

Abstract
Despite the existence of established treatments for hepatitis C virus (HCV), more effective means of preventing infection, such as a vaccine, are arguably needed to help reduce substantial global morbidity and mortality. Given the expected challenges of developing such a vaccine among those at heightened risk of infection, controlled human infection studies seem to be a promising potential approach to HCV vaccine development, but they raise substantial ethical and practical concerns. In this article, we describe some of the challenges related to the possibility of using controlled human infection studies to accelerate HCV vaccine development. The related ethical and practical concerns require further deliberation before such studies are planned and implemented.
The Structure and Behavioral Effects of Revealed Social Identity Preferences*
Authors: Hett Florian , Mechtel Mario , Kröll Markus 
Published: May 2020

AbstractA large body of evidence shows that social identity affects behaviour. However, our understanding of the substantial variation of these behavioural effects is still limited. We use a novel laboratory experiment to measure differences in preferences for social identities as a potential source of behavioural heterogeneity. Facing a trade-off between monetary payments and belonging to different groups, individuals are willing to forego significant earnings to avoid belonging to certain groups. We then show that individual differences in these foregone earnings correspond to the differences in discriminatory behaviour towards these groups. Our results illustrate the importance of considering individual heterogeneity to fully understand the behavioural effects of social identity.
The gold standard, fiscal dominance and financial supervision in Greece and South-East Europe, 1841–1939
Authors: Morys Matthias 
Published: May 2020

AbstractWe add a historical and regional dimension to the debate on the Greek debt crisis by analysing repeated cycles of entry and exit from the gold standard, government default, and financial supervision for four South-East European countries from political independence to World War II. The prevailing pattern of fiscal dominance was broken only under financial supervision, when conditionality scaled back the treasury’s influence; only then were central banks able to stabilize their exchange rates. A political economy analysis for Greece finds that financial supervision was politically acceptable as it made successfully adhering to gold more likely in the view of contemporaries.
Understanding the factors influencing the implementation of participatory interventions to improve care coordination. An analytical framework based on an evaluation in Latin America
Authors: Vargas Ingrid , Eguiguren Pamela , Mogollón-Pérez Amparo-Susana , Bertolotto Fernando , Samico Isabella , López Julieta , De Paepe Pierre , Vázquez María-Luisa 
Published: May 2020

Abstract
Healthcare coordination is considered key to improving care quality. Although participatory action research (PAR) has been used effectively to bridge the gap between evidence and practice in other areas, little is known about the key success factors of its use in healthcare organizations. This article analyses the factors influencing the implementation of PAR interventions to improve clinical coordination from the perspective of actors in public healthcare networks of Brazil, Chile, Colombia, Mexico and Uruguay. A qualitative, descriptive-interpretative study was conducted in each country’s healthcare network. Focus groups and semi-structured individual interviews were conducted to a criterion sample of: local steering committee (LSC) (29), professional platform (PP) (28), health professionals (49) and managers (28). Thematic content analysis was conducted, segmented by country and themes. The PAR process led by the LSC covered the return of baseline results, selection of problems and interventions and design, implementation and adjustment of the intervention, with PP. Interventions were implemented to improve communication and clinical agreement between primary and secondary care. Results reveal that contextual factors, the PAR process and the intervention’s content influenced their implementation, interacting across time. First, institutional support providing necessary resources, and professionals’ and managers’ willingness to participate, emerge as contextual pivotal factors, influenced by other factors related to: the system (alignment with policy and political cycle), networks (lack of time due to work overload and inadequate working conditions) and individuals (not knowing each other and mutual mistrust). Second, different characteristics of the PAR process have a bearing, in turn, on institutional support and professionals’ motivation: participation, flexibility, consensual decision-making, the LSC’s leadership and the facilitating role of researchers. Evidence is provided that implementation through an adequate PAR process can become a factor of motivation and cohesion that is crucial to the adoption of care coordination interventions, leading to better results when certain contextual factors converge.
Time as an outcome measure in fertility-related clinical studies: long-awaited
Authors: Sunkara Sesh K , Zheng Wenjing , D’Hooghe Thomas , Longobardi Salvatore , Boivin Jacky 
Published: May 2020

Abstract
Time taken to achieve a live birth is an important consideration that is central to managing patient expectations during infertility treatment. However, time-related endpoints are not reported as standard in the majority of fertility-related clinical studies and there is no internationally recognized consensus definition for such endpoints. There is, therefore, a need for meaningful discussions around the selection of appropriate time-related treatment outcome measures for studies evaluating fertility treatments that will be relevant to diverse stakeholders (e.g. patients, healthcare professionals, clinical scientists, authorities and industry). Here, we provide a proposal for the evaluation of time-related outcome measures in fertility-related clinical studies, alongside associated definitions.
Responsiveness of the Patient-reported Outcomes Measurement Information System (PROMIS) Pediatric Measures to Changes in Disease Status and Quality of Life Among Children and Adolescents With Crohn’s Disease
Authors: Brenner Erica J , Long Millie D , Mann Courtney M , Chen Wenli , Reyes Camila , Lin Li , Reeve Bryce B , Kappelman Michael D 
Published: May 2020

Abstract

Background
PROMIS Pediatric domains provide self-reported measures of physical, emotional, and social health in children with chronic conditions. We evaluated the responsiveness of the PROMIS Pediatric measures to changes in disease activity and disease-specific, health-related quality of life (HRQOL) in children with Crohn’s disease (CD).

Methods
IBD Partners Kids & Teens is an internet-based cohort of children with inflammatory bowel disease (IBD). Participants age 9 to 17 report symptoms related to disease activity (short Crohn’s Disease Activity Index [sCDAI]), the IMPACT-III HRQOL measure, and 5 PROMIS Pediatric domains. We conducted longitudinal analyses using mixed linear models to examine the extent to which PROMIS Pediatric measures respond to changes in sCDAI and IMPACT-III.

Results
Our study sample included 544 participants with CD (mean age 13 years, 44% female). All PROMIS Pediatric domains responded to changes in sCDAI, indicating improved physical, emotional, and social health, corresponding to improved disease activity and the converse (P &lt; 0.001). Observed effect estimates ranged from 1.8 for peer relationships to 6.8 for fatigue. Of 246 participants with 2 or more completed reports, disease activity was stable in 527, worse in 72, and improved in 67. Changes in PROMIS Pediatric scores were associated with changes in IMPACT-III (r = −0.43 for anxiety, r = −0.45 for depressive symptoms, r = −0.43 for pain interference, r = −0.59 for fatigue, and r = 0.23 for peer relationships).

Conclusions
This study provides evidence for the longitudinal responsiveness of the PROMIS Pediatric measures to change in disease status and HRQOL in pediatric CD patients.
Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 via Close Contact and Respiratory Droplets Among Human Angiotensin-Converting Enzyme 2 Mice
Authors: Bao Linlin , Gao Hong , Deng Wei , Lv Qi , Yu Haisheng , Liu Mingya , Yu Pin , Liu Jiangning , Qu Yajin , Gong Shuran , Lin Kaili , Qi Feifei , Xu Yanfeng , Li Fengli , Xiao Chong , Xue Jing , Song Zhiqi , Xiang Zhiguang , Wang Guanpeng , Wang Shunyi , Liu Xing , Zhao Wenjie , Han Yunlin , Wei Qiang , Qin Chuan 
Published: May 2020

Abstract
We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations.
Relationships Between Maternal Antibody Responses and Early Childhood Infection With Kaposi Sarcoma-Associated Herpesvirus
Authors: Poppe Lisa K , Kankasa Chipepo , Wood Charles , West John T 
Published: May 2020

Abstract
While mother-to-child transmission is believed to play in important role in early childhood infection with Kaposi sarcoma-associated herpesvirus (KSHV), the maternal immune response remains largely uncharacterized. This study aimed to characterize the longitudinal humoral response to KSHV in a cohort of HIV-infected Zambian mothers without KS and identify potential factors that may influence transmission. In total, 86/124 (69.4%) mothers were found to be KSHV seropositive. Longitudinal KSHV titers were fairly stable over time, although seroreversion was still common. Of the total 124 mothers, 81 had at least 1 child KSHV seroconvert during the 2 years analyzed, while the remaining 43 mothers had KSHV-seronegative children. Mothers of KSHV-negative children had higher geometric mean titers than mothers of KSHV-positive children; however, there was no difference in the presence of neutralizing antibodies. This suggests that a strong anti-KSHV immune response, and potentially nonneutralizing antibodies, may reduce transmission.
Quality assessment of weekend discharge: a systematic review and meta-analysis
Authors: Chiu Chia-Yu , Oria David , Yangga Peter , Kang Dasol 
Published: May 2020

AbstractPurposeHospital bed utility and length of stay affect the healthcare budget and quality of patient care. Prior studies already show admission and operation on weekends have higher mortality rates compared with weekdays, which has been identified as the ‘weekend effect.’ However, discharges on weekends are also linked with quality of care, and have been evaluated in the recent decade with different dimensions. This meta-analysis aims to discuss weekend discharges associated with 30-day readmission, 30-day mortality, 30-day emergency department visits and 14-day follow-up visits compared with weekday discharges.Data sourcesPubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched from January 2000 to November 2019.Study selectionPreferred reporting items for systematic reviews and meta-analyses guidelines were followed. Only studies published in English were reviewed. The random-effects model was applied to assess the effects of heterogeneity among the selected studies.Data extractionYear of publication, country, sample size, number of weekday/weekend discharges, 30-day readmission, 30-day mortality, 30-day ED visits and 14-day appointment follow-up rate.Results of data synthesisThere are 20 studies from seven countries, including 13 articles from America, in the present meta-analysis. There was no significant difference in odds ratio (OR) in 30-day readmission, 30-day mortality, 30-day ED visit, and 14-day follow-up between weekday and weekend. However, the OR for 30-day readmission was significantly higher among patients in the USA, including studies with high heterogeneity.ConclusionIn the USA, the 30-day readmission rate was higher in patients who had been discharged on the weekend compared with the weekday. However, interpretation should be cautious because of data limitation and high heterogeneity. Further intervention should be conducted to eliminate any healthcare inequality within the healthcare system and to improve the quality of patient care.
Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model
Authors: Lodise Thomas P , Smith Nicolas M , O’Donnell Nick , Eakin Ann E , Holden Patricia N , Boissonneault Katie Rose , Zhou Jieqiang , Tao Xun , Bulitta Jürgen B , Fowler Vance G , Chambers Henry F , Bonomo Robert A , Tsuji Brian T 
Published: May 2020

Abstract

Background
MBL-producing strains of Enterobacteriaceae are a major public health concern. We sought to define optimal combination regimens of ceftazidime/avibactam with aztreonam in a hollow-fibre infection model (HFIM) of MBL-producing strains of Escherichia coli and Klebsiella pneumoniae.

Methods
E. coli ARLG-1013 (blaNDM-1, blaCTX-M, blaCMY, blaTEM) and K. pneumoniae ARLG-1002 (blaNDM-1, blaCTXM-15, blaDHA, blaSHV, blaTEM) were studied in the HFIM using simulated human dosing regimens of ceftazidime/avibactam and aztreonam. Experiments were designed to evaluate the effect of staggered versus simultaneous administration, infusion duration and aztreonam daily dose (6 g/day versus 8 g/day) on bacterial killing and resistance suppression. Prospective validation experiments for the most active combination regimens were performed in triplicate to ensure reproducibility.

Results
Staggered administration of the combination (ceftazidime/avibactam followed by aztreonam) was found to be inferior to simultaneous administration. Longer infusion durations (2 h and continuous infusion) also resulted in enhanced bacterial killing relative to 30 min infusions. The rate of killing was more pronounced with 8 g/day versus 6 g/day aztreonam combination regimens for both tested strains. In the prospective validation experiments, ceftazidime/avibactam with aztreonam dosed every 8 and 6 h, respectively (ceftazidime/avibactam 2/0.5 g every 8 h + aztreonam 2 g every 6 h), or ceftazidime/avibactam with aztreonam as continuous infusions resulted in maximal bacterial killing and resistance suppression over 7 days.

Conclusions
Simultaneous administration of aztreonam 8 g/day given as a continuous or 2 h infusion with ceftazidime/avibactam resulted in complete bacterial eradication and resistance suppression. Further study of this combination is needed with additional MBL-producing Gram-negative pathogens. The safety of this double β-lactam strategy also warrants further study in Phase 1 clinical trials.
Efficacy, metabolism and pharmacokinetics of Ro 15-5458, a forgotten schistosomicidal 9-acridanone hydrazone
Authors: Probst Alexandra , Häberli Cécile , Siegel Dionicio , Huang Jianbo , Vigneron Seth , Ta Anh P , Skinner Danielle E , El-Sakkary Nelly , Momper Jeremiah D , Gangoiti Jon , Dong Yuxiang , Vennerstrom Jonathan L , Charman Susan A , Caffrey Conor R , Keiser Jennifer 
Published: May 2020

AbstractBackgroundTreatment of schistosomiasis, a neglected disease, relies on just one partially effective drug, praziquantel. We revisited the 9-acridanone hydrazone, Ro 15-5458, a largely forgotten antischistosomal lead compound.MethodsRo 15-5458 was evaluated in juvenile and adult Schistosoma mansoni-infected mice. We studied dose–response, hepatic shift and stage specificity. The metabolic stability of Ro 15-5458 was measured in the presence of human and mouse liver microsomes, and human hepatocytes; the latter also served to identify metabolites. Pharmacokinetic parameters were measured in naive mice. The efficacy of Ro 15-5458 was also assessed in S. haematobium-infected hamsters and S. japonicum-infected mice.ResultsRo 15-5458 had single-dose ED50 values of 15 and 5.3 mg/kg in mice harbouring juvenile and adult S. mansoni infections, respectively. An ED50 value of 17 mg/kg was measured in S. haematobium-infected hamsters; however, the compound was inactive at up to 100 mg/kg in S. japonicum-infected mice. The drug-induced hepatic shift occurred between 48 and 66 h post treatment. A single oral dose of 50 mg/kg of Ro 15-5458 had high activity against all tested S. mansoni stages (1-, 7-, 14-, 21- and 49-day-old). In vitro, human hepatocytes produced N-desethyl and glucuronide metabolites; otherwise Ro 15-5458 was metabolically stable in the presence of microsomes or whole hepatocytes. The maximum plasma concentration was approximately 8.13 μg/mL 3 h after a 50 mg/kg oral dose and the half-life was approximately 4.9 h.ConclusionsRo 15-5458 has high activity against S. mansoni and S. haematobium, yet lacks activity against S. japonicum, which is striking. This will require further investigation, as a broad-spectrum antischistosomal drug is desirable.
Establishing metastatic patient-derived xenograft model for colorectal cancer
Authors: Zhang Yanmei , Lee Sau Har , Wang Cheng , Gao Yunhe , Li Jiyang , Xu Wei 
Published: May 2020

Abstract

Background
Patient-derived xenograft model is a powerful and promising tool for drug discovery and cancer biology studies. The application of previous metastatic colorectal cancer models has been greatly limited by its low success rate and long time to develop metastasis. Therefore, in this study, we aim to describe an optimized protocol for faster establishment of colorectal cancer metastatic patient-derived xenograft mouse models.

Methods
Smaller micro tissues (˂150 μm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours.

Results
About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients’ tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active β-catenin, Ki-67 and α smooth muscle actin when compared with the original patients’ tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin.

Conclusions
Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.
Sublobar resection versus lobectomy for patients with resectable stage I non-small cell lung cancer with idiopathic pulmonary fibrosis: a phase III study evaluating survival (JCOG1708, SURPRISE)
Authors: Tanaka Kiyo , Tsutani Yasuhiro , Wakabayashi Masashi , Mizutani Tomonori , Aokage Keiju , Miyata Yoshihiro , Kuroda Hiroaki , Saji Hisashi , Watanabe Shun-ichi , Okada Morihito ,   behalf of the Lung Cancer Surgical Study Group/Japan Clinical Oncology Group
Published: May 2020

Abstract
The standard treatment for the patients with surgically resectable early non-small cell lung cancer (NSCLC) is lung lobectomy. However, if patients have idiopathic pulmonary fibrosis combined with early stage lung cancer, there is no standard treatment for this population. Patients with idiopathic pulmonary fibrosis have chronic progressive decline in respiratory function; thus, the preservation of respiratory function is essential. The aim of this trial is to confirm the clinical effectiveness of sublobar resection such as wedge resection or segmentectomy for early NSCLC with idiopathic pulmonary fibrosis compared with lobectomy in a randomized phase III trial. The primary endpoint is overall survival. If the non-inferiority of overall survival and minimal invasiveness are proven, it can be a new standard treatment for early NSCLC with idiopathic pulmonary fibrosis. A planned total 430 patients will be enrolled from 50 institutions over 5 years. This trial has been registered in the UMIN Clinical Trials Registry with code UMIN000032696 [http://www.umin.ac.jp/ctr/index.htm].