bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive, Agentic, Apathetic, or Challenged? Aging, Emotion, and Coping During the COVID-19 Pandemic
Authors: Young Nathaniel A , Waugh Christian E , Minton Alyssa R , Charles Susan T , Haase Claudia M , Mikels Joseph A 
Published: December 2020

Abstract

Background and Objectives
Advanced age is generally associated with improved emotional well-being, but the coronavirus 2019 pandemic unleashed a global stressor that gravely threatened the physical well-being and ostensibly challenged the emotional well-being of older adults disproportionately. The current study investigated differences in emotional experiences and coping strategies between younger and older adults during the pandemic, and whether these differences were accounted for by age differences in appraisal of the pandemic.

Research Design and Methods
We asked younger (n = 181) and older (n = 176) adult participants to report their stress, appraisals of the pandemic, emotions, and the ways in which they were coping with the pandemic.

Results
Results indicated that older adults experienced less stress and less negative affect and used greater problem-focused coping and less avoidant coping in response to the pandemic than younger adults. Furthermore, age differences in affect and coping were partially accounted for by age differences in appraisals of the pandemic.

Discussion and Implications
Despite their objectively higher risk of illness and death due to the pandemic, older adults experienced less negative affect and used more agentic coping strategies than younger adults.
Free-Riding for the Common Good? Generics, Biosimilars and References to Originator Trademarks in Comparative Advertising in France
Authors: Rouvinen Markus 
Published: December 2020

Abstract
Generic and biosimilar medicines are fiscally advantageous products in relation to which the generally applicable EU rules governing comparative advertising seemingly conflict with national healthcare policy. This article argues that the permissive stance of the French courts on the use of the trademarked names of originator medicines in advertising for generics appears inconsistent with the case law of the Court of Justice of the European Union as it stands in relation to Art. 4(f) of Directive 2006/114/EC on misleading and comparative advertising. This gives rise to an undesirable divergence in the application of the Directive between Member States, suggesting that further guidance is needed on the application of the provision to generic-originator comparisons. It is submitted that treating generic drugs with particular leniency is unjustified given the detrimental effect the use of originator trademarks by the marketers of generics and biosimilars may have on the ability of the originator trademark to stimulate investment into manufacturing quality. The issue of the degree to which the use of originator trademarks in advertising promoting generics and biosimilars should be permitted serves as a poignant example of the delicate balance required for comparative advertising to increase consumer choice whilst simultaneously protecting competitors from advertising that may ultimately be detrimental to undistorted competition in the Single Market.
Bayesian spatio-temporal modelling and prediction of areal demands for ambulance services
Authors: Nicoletta Vittorio , Guglielmi Alessandra , Ruiz Angel , Bélanger Valérie , Lanzarone Ettore 
Published: December 2020

Abstract
Careful planning of an ambulance service is critical to reduce response times to emergency calls and make assistance more effective. However, the demand for emergency services is highly variable, and good prediction of the number of future emergency calls, and their spatial and temporal distribution, is challenging. In this work, we propose a Bayesian approach to predict the number of emergency calls in future time periods for each zone of the served territory. The number of calls is described by a generalized linear mixed effects model, and inference, in terms of posterior predictive distributions, is obtained through Markov chain Monte Carlo simulation. Our approach is applied in a large city in Canada. The paper demonstrates that using a model for areal data provides good results in terms of predictive accuracy and allows flexibility in accounting for the main features of the dataset. Moreover, it shows the computational efficiency of the approach despite the huge dataset.
Burden of Respiratory Syncytial Virus Infection During the First Year of Life
Authors: Thomas Emilia , Mattila Janna-Maija , Lehtinen Pasi , Vuorinen Tytti , Waris Matti , Heikkinen Terho 
Published: December 2020

Abstract

Background
Although many infants with respiratory syncytial virus (RSV) infection are hospitalized, most infants are treated as outpatients. Limited data are available on the burden of RSV in outpatient infants.

Methods
In a prospective study, we enrolled 431 newborn infants and followed them up for a 10-month period (September–June). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for the detection of RSV. The parents completed daily symptom diaries throughout the study.

Results
Among 408 active participants, the seasonal incidence rate of RSV illness was 328.4 per 1000 (95% confidence interval [CI], 275.2–389.0). Infants with ≥1 sibling had a 1.9-fold higher incidence of RSV illness than those without siblings (95% CI, 1.3–2.8; P &lt; .001). Acute otitis media developed in 103 (76.9%) of 134 infants with RSV infection, and 95 (70.9%) were treated with antibiotics. Nine infants with RSV (6.7%) were hospitalized, for a seasonal incidence rate of RSV hospitalization of 22.1 per 1000 (95% CI, 10.1–41.9).

Conclusions
The outpatient burden of RSV is heavy on infants during the first year of life. Acute otitis media is a frequent complication of RSV, and it should be included in cost-effectiveness analyses of prevention or treatment of RSV infections in infants.
Synthesis, inhibitory activity and oral dosing formulation of AV5124, the structural analogue of influenza virus endonuclease inhibitor baloxavir
Authors: Ivashchenko Andrei A , Mitkin Oleg D , Jones Jeremy C , Nikitin Alexander V , Koryakova Angela G , Karapetian Ruben N , Kravchenko Dmitry V , Mochalov Stephan V , Ryakhovskiy Alexey A , Aladinskiy Vladimir , Leneva Irina A , Falynskova Irina N , Glubokova Ekaterina A , Govorkova Elena A , Ivachtchenko Alexandre V 
Published: December 2020

Abstract

Background
The development and clinical implementation of the cap-dependent endonuclease (CEN) inhibitor baloxavir marboxil was a breakthrough in influenza therapy, but it was associated with the emergence of drug-resistant variants.

Objectives
To design and synthesize structural analogues of CEN inhibitors and evaluate their safety, pharmacokinetics and antiviral potency in vitro and in vivo.

Methods
The drug candidate AV5124 and its active metabolite AV5116 were synthesized based on pharmacophore modelling. Stability in plasma and microsomes, plasma protein binding, cytotoxicity and antiviral activities were assessed in vitro. Pharmacokinetics after IV or oral administration were analysed in CD-1 mice. Acute toxicity and protective efficacy against lethal A(H1N1)pdm09 influenza virus challenge were examined in BALB/c mice.

Results
Pharmacophore model-assisted, 3D molecular docking predicted key supramolecular interactions of the metal-binding group and bulky hydrophobic group of AV5116 with the CEN binding site (Protein Data Bank code: 6FS6) that are essential for high antiviral activity. AV5116 inhibited influenza virus polymerase complexes in cell-free assays and replication of oseltamivir-susceptible and -resistant influenza A and B viruses at nanomolar concentrations. Notably, AV5116 was equipotent or more potent than baloxavir acid (BXA) against WT (I38-WT) viruses and viruses with reduced BXA susceptibility carrying an I38T polymerase acidic (PA) substitution. AV5116 exhibited low cytotoxicity in Madin–Darby canine kidney cells and lacked mitochondrial toxicity, resulting in favourable selective indices. Treatment with 20 or 50 mg/kg AV5124 prevented death in 60% and 100% of animals, respectively.

Conclusions
Overall, AV5124 and A5116 are promising inhibitors of the influenza virus CEN and warrant further development as potent anti-influenza agents.
Fully Automated Optical Hematocrit Measurement from Dried Blood Spots
Authors: Luginbühl Marc , Fischer Yannick , Gaugler Stefan 
Published: December 2020

Abstract
The impact of the hematocrit (HCT) on the dried blood spot (DBS)’s spreading area is one of the most important hurdles, which prevents the full acceptance of quantitative microsampling strategies. Several destructive and non-destructive strategies to assess the HCT from a DBS post-sampling have been presented. Unfortunately, the current methods are either labor-intensive, require a complicated algorithm or are not automatable. Here, we present a novel setup that permits the fully automated reflectance analysis to measure the HCT from a DBS. The underlying principle is based on the concept of the non-destructive single-wavelength HCT measurement. The novel module was embedded within the DBS-MS 500 platform to enable high-throughput analysis of HCT values in combination with automated DBS extraction. The novel setup was assessed and optimized for the probe to card distance, stability, anti-coagulant, spotting volume, scan number, calibration variability, accuracy and precision. It showed excellent inter-day (≤3.7%) and intra-day (≤1.16%) precision as well as high accuracy when analyzing authentic samples (101% ± 7% [range: 87–127%]). Besides, the simple and straightforward application of an HCT correction for DBS was demonstrated during a pharmacokinetic study with diclofenac involving three subjects. Thereby, the sample’s HCT and the HCT impact on the analyte were assessed and compensated. In conclusion, the novel setup enables quantitative analysis of non-volumetric samples in an automated fashion without compromising the concept of cost-effective, minimally invasive sampling.
The WOX family transcriptional regulator SlLAM1 controls compound leaf and floral organ development inSolanum lycopersicum
Authors: Wang Chaoqun , Zhao Baolin , He Liangliang , Zhou Shaoli , Liu Ye , Zhao Weiyue , Guo Shiqi , Wang Ruoruo , Bai Quanzi , Li Youhan , Wang Dongfa , Wu Qing , Yang Yuanfan , Liu Yu , Tadege Million , Chen Jianghua 
Published: December 2020

AbstractPlant-specific WOX family transcription factors play important roles ranging from embryogenesis to lateral organ development. The WOX1 transcription factors, which belong to the modern clade of the WOX family, are known to regulate outgrowth of the leaf blade specifically in the mediolateral axis; however, the role of WOX1 in compound leaf development remains unknown. Phylogenetic analysis of the whole WOX family in tomato (Solanum lycopersicum) indicates that there are 10 members that represent the modern, intermediate, and ancient clades. Using phylogenetic analysis and a reverse genetic approach, in this study we identified SlLAM1 in the modern clade and examined its function and tissue-specific expression pattern. We found that knocking out SlLAM1 via CRISPR/Cas9-mediated genome editing led to narrow leaves and a reduced number of secondary leaflets. Overexpression of tomato SlLAM1 could rescue the defects of the tobacco lam1 mutant. Anatomical and transcriptomic analyses demonstrated that floral organ development, fruit size, secondary leaflet initiation, and leaf complexity were altered due to loss-of-function of SlLAM1. These findings demonstrate that tomato SlLAM1 plays an important role in the regulation of secondary leaflet initiation, in addition to its conserved function in blade expansion.
Abortion Rights after Artificial Wombs: Why Decriminalisation is Needed Ahead of Ectogenesis
Authors: Horn Claire 
Published: December 2020

Abstract
Significant scientific progress has been made toward artificial womb technology, which would allow part of human gestation to occur outside the body. Bioethical and legal scholars have argued that artificial wombs will challenge defences of abortion based in arguments for protecting bodily autonomy, for a pregnant person could have the foetus transferred to an artificial womb instead of being terminated. Drawing on examples from the common law jurisdictions of Canada, the USA, and the UK, I assess three ways scholars have argued abortion might be defended after ectogenesis (through redefining foetal viability, through a property right, and through a right to avoid genetic parenthood). I argue that while each of these proposals has strategic merit, each has significant legal and ethical limitations. Taking the normative position that abortion will remain a vital healthcare resource, I make the case for protecting abortion rights from a challenge posed by ectogenesis by focusing on decriminalisation.
Phylogenetic Analysis of SARS-CoV-2 Data Is Difficult
Authors: Morel Benoit , Barbera Pierre , Czech Lucas , Bettisworth Ben , Hübner Lukas , Lutteropp Sarah , Serdari Dora , Kostaki Evangelia-Georgia , Mamais Ioannis , Kozlov Alexey M , Pavlidis Pavlos , Paraskevis Dimitrios , Stamatakis Alexandros 
Published: December 2020

AbstractNumerous studies covering some aspects of SARS-CoV-2 data analyses are being published on a daily basis, including a regularly updated phylogeny on nextstrain.org. Here, we review the difficulties of inferring reliable phylogenies by example of a data snapshot comprising a quality-filtered subset of 8,736 out of all 16,453 virus sequences available on May 5, 2020 from gisaid.org. We find that it is difficult to infer a reliable phylogeny on these data due to the large number of sequences in conjunction with the low number of mutations. We further find that rooting the inferred phylogeny with some degree of confidence either via the bat and pangolin outgroups or by applying novel computational methods on the ingroup phylogeny does not appear to be credible. Finally, an automatic classification of the current sequences into subclasses using the mPTP tool for molecular species delimitation is also, as might be expected, not possible, as the sequences are too closely related. We conclude that, although the application of phylogenetic methods to disentangle the evolution and spread of COVID-19 provides some insight, results of phylogenetic analyses, in particular those conducted under the default settings of current phylogenetic inference tools, as well as downstream analyses on the inferred phylogenies, should be considered and interpreted with extreme caution.
Splicing at the phase-separated nuclear speckle interface: a model
Authors: Liao Susan E , Regev Oded 
Published: December 2020

AbstractPhase-separated membraneless bodies play important roles in nucleic acid biology. While current models for the roles of phase separation largely focus on the compartmentalization of constituent proteins, we reason that other properties of phase separation may play functional roles. Specifically, we propose that interfaces of phase-separated membraneless bodies could have functional roles in spatially organizing biochemical reactions. Here we propose such a model for the nuclear speckle, a membraneless body implicated in RNA splicing. In our model, sequence-dependent RNA positioning along the nuclear speckle interface coordinates RNA splicing. Our model asserts that exons are preferentially sequestered into nuclear speckles through binding by SR proteins, while introns are excluded through binding by nucleoplasmic hnRNP proteins. As a result, splice sites at exon-intron boundaries are preferentially positioned at nuclear speckle interfaces. This positioning exposes splice sites to interface-localized spliceosomes, enabling the subsequent splicing reaction. Our model provides a simple mechanism that seamlessly explains much of the complex logic of splicing. This logic includes experimental results such as the antagonistic duality between splicing factors, the position dependence of splicing sequence motifs, and the collective contribution of many motifs to splicing decisions. Similar functional roles for phase-separated interfaces may exist for other membraneless bodies.
Differential activation mechanisms of two isoforms of Gcr1 transcription factor generated from spliced and un-spliced transcripts inSaccharomyces cerevisiae
Authors: Cha Seungwoo , Hong Chang Pyo , Kang Hyun Ah , Hahn Ji-Sook 
Published: December 2020

AbstractGcr1, an important transcription factor for glycolytic genes in Saccharomyces cerevisiae, was recently revealed to have two isoforms, Gcr1U and Gcr1S, produced from un-spliced and spliced transcripts, respectively. In this study, by generating strains expressing only Gcr1U or Gcr1S using the CRISPR/Cas9 system, we elucidate differential activation mechanisms of these two isoforms. The Gcr1U monomer forms an active complex with its coactivator Gcr2 homodimer, whereas Gcr1S acts as a homodimer without Gcr2. The USS domain, 55 residues at the N-terminus existing only in Gcr1U, inhibits dimerization of Gcr1U and even acts in trans to inhibit Gcr1S dimerization. The Gcr1S monomer inhibits the metabolic switch from fermentation to respiration by directly binding to the ALD4 promoter, which can be restored by overexpression of the ALD4 gene, encoding a mitochondrial aldehyde dehydrogenase required for ethanol utilization. Gcr1U and Gcr1S regulate almost the same target genes, but show unique activities depending on growth phase, suggesting that these isoforms play differential roles through separate activation mechanisms depending on environmental conditions.
COVD-30. A SNAPSHOT OF THE IMPACT OF COVID-19 ON PATIENTS WITH NERVOUS SYSTEM TUMORS
Authors: Aaroe Ashley ,   D3CODE Team, Harrison Rebecca , Majd Nazanin , O’Brien Barbara , Weathers Shiao-Pei , Loghin Monica , Kamiya-Matsuoka Carlos , Yung W K Alfred , de Groot John , Woodman Karin 
Published: December 2020

Abstract

BACKGROUND
The impact of COVID-19 on patients with nervous system tumors is not known. This population is often immunosuppressed, susceptible to neurological complications, and requiring of frequent cancer care, all of which may confer vulnerability to poorer outcomes after infection.

METHODS
Clinical data were obtained from structured electronic medical record elements, clinical note text and laboratory RESULTS: Each source was identified, integrated and analyzed using the Palantir Foundry platform (Syntropy), part of the Context Engine Data Management System through the MD Anderson Cancer Center (MDACC) IRB approved D3CODE initiative. The population of interest was patients diagnosed with COVID-19 who had been seen at the Brain and Spine Center for nervous system tumors.

RESULTS
8,177 ambulatory patients were seen at the Brain and Spine Center from 3/1/20–9/1/20. COVID status was known for 1,753 (21%). Sixty-one (0.7%) were COVID-19 positive. Of these, 17 had primary nervous system tumors. Seven (41%) were treated in the emergency department or hospital for infection. Two were symptomatic but did not require further care. Eight were asymptomatic. Nine (53%) had alterations in cancer management within one week of COVID-19 diagnosis – delayed surgery (3), delayed/interrupted chemotherapy (2), delayed/interrupted radiation (2), cancer treatment discontinued (2). Eight patients (47%) had no clear impact of infection on their cancer treatment, three were on surveillance. Three (18%) unique patients had neurological symptoms attributed to/exacerbated by COVID-19 – encephalopathy (2), seizure (2), stroke (1).

CONCLUSION
No deleterious effects of alterations in cancer management after COVID-19 infection have been identified thus far, though longitudinal follow up is warranted. Our results suggest that COVID-19 infection frequently incurs medical complications or alterations in cancer treatment. The potential impacts of COVID-19 on our vulnerable neuro-oncology patient population should be further explored, and attention to these potential implications for our patients is warranted by treating clinicians.
Investigating Changes in Patients’ Smoking Behavior, Tobacco Dependence, and Motivation to Stop Smoking Following a “Smoke-Free” Mental Health Inpatient Stay: Results From a Longitudinal Survey in England
Authors: Ainscough Tom S , Mitchell Alex , Hewitt Catherine , Horspool Michelle , Stewart Pete , Ker Suzy , Colley Lesley , Paul Claire , Hough Phil , Hough Simon , Britton John , Ratschen Elena 
Published: December 2020

Abstract

Introduction
In line with national guidance, mental health Trusts in England are implementing complete smoke-free policies. We investigated inpatients’ changes in smoking behavior, tobacco dependence, vaping, and motivation to stop smoking between pre-admission and post-discharge.

Methods
We surveyed acute adult mental health inpatients from 14 wards in three mental health Trusts in England in 2019. Structured face-to-face and telephone interviews with patients who smoked on or during admission were conducted during the admission period and at one week and one month after discharge. Data on smoking status; daily cigarette consumption; Heaviness of Smoking Index (HSI); Strength of Urges to Smoke (SUTS); Motivation to Stop Smoking (MTSS) and vaping were collected and analyzed using regression and probit models.

Results
Inpatient smoking prevalence was 51.9%, and a total of 152 of all 555 eligible smokers (27%) were recruited. Attrition was high: 49.3% at the first and 50.7% at the second follow-up interview. Changes in self-reported smoking status, motivation to quit, and vaping did not change significantly over the study period. Cigarette consumption (p &lt; 0.001) and Heaviness of Smoking Index (p &lt; 0.001) modestly reduced. The frequency and strength of urges to smoke (p = 0.011 and 0.012, respectively) decreased modestly after discharge but were scored as high by 57% and 60% of participants during admission respectively. Just over half (56%) reported being offered smoking cessation support on admission.

Conclusions
This study identified very modest changes in smoking-related outcomes during and after admission and indicates major challenges to smoke-free policy implementation, including limited support for patients who smoke.

Implications
Despite mental health Trusts in England had developed and implemented smoke-free policies to meet national guidelines, adherence to these policies and provision of effective smoking cessation and temporary abstinence support for inpatients admitted to acute adult mental health wards appear to be limited. Patients who smoke on admission are likely to continue to do so during admission and after discharge, and only a very modest change in smoking behaviors appears to take place. Important opportunities to promote smoking cessation in this population are missed. Barriers to effective support need to be identified and addressed.
The Value of Unemployment Insurance
Authors: Landais Camille , Spinnewijn Johannes 
Published: December 2020

Abstract
Due to the absence of unemployment insurance (UI) choices, the traditional approach to estimating the value of UI is to infer it from the observed consumption response to job loss under some assumption on risk preferences. Exploiting the rich data and unique policy context in Sweden, we propose two alternative approaches that relax this assumption and we implement all three methods on the same sample of workers. The first approach considers the difference in marginal propensity to consume (MPC) when unemployed versus employed, which allows to identify the difference in prices to smooth consumption in the respective states. The second approach exploits UI choices embedded in the Swedish UI system in a Revealed Preference approach. While the drop in consumption expenditures is relatively small ($\sim$13%), we find that the MPC is around 25% higher when unemployed than employed, translating into a marginal value of transfers that is at least $60$% higher when unemployed than employed. This high value of UI is confirmed by our RP estimates and indicates substantial risk aversion given the relatively small drop in consumption expenditures.