bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cohort-based smoothing methods for age-specific contact rates
Authors: Vandendijck Yannick , Gressani Oswaldo , Faes Christel , Camarda Carlo G , Hens Niel 
Published: March 2023

Summary
The use of social contact rates is widespread in infectious disease modeling since it has been shown that they are key driving forces of important epidemiological parameters. Quantification of contact patterns is crucial to parameterize dynamic transmission models and to provide insights on the (basic) reproduction number. Information on social interactions can be obtained from population-based contact surveys, such as the European Commission project POLYMOD. Estimation of age-specific contact rates from these studies is often done using a piecewise constant approach or bivariate smoothing techniques. For the latter, typically, smoothness is introduced in the dimensions of the respondent’s and contact’s age (i.e., the rows and columns of the social contact matrix). We propose a smoothing constrained approach—taking into account the reciprocal nature of contacts—introducing smoothness over the diagonal (including all subdiagonals) of the social contact matrix. This modeling approach is justified assuming that when people age their contact behavior changes smoothly. We call this smoothing from a cohort perspective. Two approaches that allow for smoothing over social contact matrix diagonals are proposed, namely (i) reordering of the diagonal components of the contact matrix and (ii) reordering of the penalty matrix ensuring smoothness over the contact matrix diagonals. Parameter estimation is done in the likelihood framework by using constrained penalized iterative reweighted least squares. A simulation study underlines the benefits of cohort-based smoothing. Finally, the proposed methods are illustrated on the Belgian POLYMOD data of 2006. Code to reproduce the results of the article can be downloaded on this GitHub repository https://github.com/oswaldogressani/Cohort_smoothing.
Evaluating the Impact of Statin Use on Influenza Vaccine Effectiveness and Influenza Infection in Older Adults
Authors: Chung Hannah , Campitelli Michael A , Buchan Sarah A , Campigotto Aaron , Chen Branson , Crowcroft Natasha S , Dubey Vinita , Gubbay Jonathan B , Karnauchow Timothy , Katz Kevin , McGeer Allison J , McNally J Dayre , Mubareka Samira , Murti Michelle , Richardson David C , Rosella Laura C , Schwartz Kevin L , Smieja Marek , Zahariadis George , Kwong Jeffrey C 
Published: March 2023

Abstract

Background
Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk.

Methods
Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010–2011 to 2018–2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status.

Results
Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%–20%] and 17% [13%–21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10–1.21] and 1.15 [1.10–1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users.

Conclusions
Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.
Rare benign adrenal lesions
Authors: Dogra Prerna , Sundin Anders , Juhlin C Christofer , Calissendorff Jan , Falhammar Henrik , Bancos Irina 
Published: March 2023

AbstractWhile most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.
Nudges and threats: soft versus hard incentives for tax compliance
Authors: Andersson Henrik , Engström Per , Nordblom Katarina , Wanander Susanna 
Published: March 2023

Abstract
We study what induces delinquent wage earners to pay their taxes due, using high-quality administrative data from the Swedish Tax Agency. We find a strong effect of the standard enforcement regime: a threat of having the debt handed over to the Enforcement Agency increases payments by more than 9 percentage points (from a baseline of 58%). When including actual enforcement, payment increases by 19 percentage points compared with those who do not risk enforcement. In a field experiment, we compare these effects of standard enforcement to those involving much milder nudges, consisting of letters reminding tax delinquents to pay their taxes due. We find that a ‘pure nudge’ (i.e., the inclusion of an extra sheet of paper with no valuable information) has an effect of around 7 percentage points for those who do not risk enforcement upon non-payment, that is, an effect almost as large as for the threat of enforcement. However, the same nudge has no detectable effect on the group that is subject to enforcement. Finally, we find a small additional effect on payments from social norm messages both for those who risk enforcement and for those who do not.
Vitamin D in atherosclerosis and cardiovascular events
Authors: Carbone Federico , Liberale Luca , Libby Peter , Montecucco Fabrizio 
Published: March 2023

AbstractBoth experimental and clinical findings linking vitamin D to cardiovascular (CV) risk have prompted consideration of its supplementation to improve overall health. Yet several meta-analyses do not provide support for the clinical effectiveness of this strategy. Meanwhile, the understanding of the roles of vitamin D in the pathophysiology of CV diseases has evolved. Specifically, recent work has revealed some non-classical pleiotropic effects of vitamin D, increasing the complexity of vitamin D signalling. Within particular microenvironments (e.g. dysfunctional adipose tissue and atherosclerotic plaque), vitamin D can act locally at cellular level through intracrine/autocrine/paracrine feedforward and feedback circuits. Within atherosclerotic tissues, ‘local’ vitamin D levels may influence relevant systemic consequences independently of its circulating pool. Moreover, vitamin D links closely to other signalling pathways of CV relevance including those driving cellular senescence, ageing, and age-related diseases—among them CV conditions. This review updates knowledge on vitamin D biology aiming to clarify the widening gap between experimental and clinical evidence. It highlights the potential reverse causation confounding correlation between vitamin D status and CV health, and the need to consider novel pathophysiological concepts in the design of future clinical trials that explore the effects of vitamin D on atherosclerosis and risk of CV events.
Exposomics as a tool to investigate differences in health and disease by sex and gender
Authors: Bucher Meghan L , Anderson Faith L , Lai Yunjia , Dicent Jocelyn , Miller Gary W , Zota Ami R 
Published: March 2023

AbstractThe health and disease of an individual is mediated by their genetics, a lifetime of environmental exposures, and interactions between the two. Genetic or biological sex, including chromosome composition and hormone expression, may influence both the types and frequency of environmental exposures an individual experiences, as well as the biological responses an individual has to those exposures. Gender identity, which can be associated with social behaviors such as expressions of self, may also mediate the types and frequency of exposures an individual experiences. Recent advances in exposome-level analysis have progressed our understanding of how environmental factors affect health outcomes; however, the relationship between environmental exposures and sex- and gender-specific health remains underexplored. The comprehensive, non-targeted, and unbiased nature of exposomic research provides a unique opportunity to systematically evaluate how environmental exposures interact with biological sex and gender identity to influence health. In this forward-looking narrative review, we provide examples of how biological sex and gender identity influence environmental exposures, discuss how environmental factors may interact with biological processes, and highlight how an intersectional approach to exposomics can provide critical insights for sex- and gender-specific health sciences.
Quantification of the mobility potential of antibiotic resistance genes through multiplexed ddPCR linkage analysis
Authors: de la Cruz Barron Magali , Kneis David , Elena Alan Xavier , Bagra Kenyum , Berendonk Thomas U , Klümper Uli 
Published: March 2023

AbstractThere is a clear need for global monitoring initiatives to evaluate the risks of antibiotic resistance genes (ARGs) towards human health. Therefore, not only ARG abundances within a given environment, but also their potential mobility, hence their ability to spread to human pathogenic bacteria needs to be quantified. We developed a novel, sequencing-independent method for assessing the linkage of an ARG to a mobile genetic element by statistical analysis of multiplexed droplet digital PCR (ddPCR) carried out on environmental DNA sheared into defined, short fragments. This allows quantifying the physical linkage between specific ARGs and mobile genetic elements, here demonstrated for the sulfonamide ARG sul1 and the Class 1 integron integrase gene intI1. The method's efficiency is demonstrated using mixtures of model DNA fragments with either linked and unlinked target genes: Linkage of the two target genes can be accurately quantified based on high correlation coefficients between observed and expected values (R2) as well as low mean absolute errors (MAE) for both target genes, sul1 (R2 = 0.9997, MAE = 0.71%, n = 24) and intI1 (R2 = 0.9991, MAE = 1.14%, n = 24). Furthermore, we demonstrate that adjusting the fragmentation length of DNA during shearing allows controlling rates of false positives and false negative detection of linkage. The presented method allows rapidly obtaining reliable results in a labor- and cost-efficient manner.
Development of vitamin B12 dependency inSaccharomyces cerevisiae
Authors: Lehner Sandra , Boles Eckhard 
Published: March 2023

AbstractFor decades, the industrial vitamin B12 (cobalamin) production has been based on bacterial producer strains. Due to limited methods for strain optimization and difficult strain handling, the desire for new vitamin B12-producing hosts has risen. As a vitamin B12-independent organism with a big toolbox for genomic engineering and easy-to-handle cultivation conditions, Saccharomyces cerevisiae has high potential for heterologous vitamin B12 production. However, the B12 synthesis pathway is long and complex. To be able to easily engineer and evolve B12-producing recombinant yeast cells, we have developed an S. cerevisiae strain whose growth is dependent on vitamin B12. For this, the B12-independent methionine synthase Met6 of yeast was replaced by a B12-dependent methionine synthase MetH from Escherichia coli. Adaptive laboratory evolution, RT-qPCR, and overexpression experiments show that additional high-level expression of a bacterial flavodoxin/ferredoxin-NADP+ reductase (Fpr-FldA) system is essential for in vivo reactivation of MetH activity and growth. Growth of MetH-containing yeast cells on methionine-free media is only possible with the addition of adenosylcobalamin or methylcobalamin. A heterologous vitamin B12 transport system turned out to be not necessary for the uptake of cobalamins. This strain should be a powerful chassis to engineer B12-producing yeast cells.
Exceptional case of aortic atresia associated with atypical double aortic arch
Authors: Krokovay Anna , Cavigelli-Brunner Anna , Kretschmar Oliver , Cesnjevar Robert 
Published: March 2023

AbstractWe present the unique case of atretic aortic valve associated with hypoplastic ascending aorta and double aortic arch of unusual configuration supplying retrograde blood flow to the coronary arteries.
Impact of unplanned pregnancy on neonatal outcomes: findings of new high-risk newborns in Peru
Authors: Ticona Diana Manuela , Huanco Diana , Ticona-Rendón Manuel Benedicto 
Published: March 2023

Abstract

Background
Unplanned pregnancy is a significant public health problem, especially in low- to middle-income countries. The objective of this study was to determine the neonatal outcomes associated with unplanned pregnancy in a public hospital in southern Peru.

Methods
A cross-sectional analytical study was conducted from June to August 2021 among 306 mothers and their newborns selected by convenience sampling. After obtaining informed consent, mothers were surveyed during their postpartum hospitalization about their pregnancy intentions. Unintended pregnancy was considered when it was mistimed or unwanted. Neonatal outcomes were assessed by reviewing medical records prior to discharge, evaluating the presence of low birth weight, insufficient birth weight, prematurity, respiratory distress syndrome, sepsis and neonatal mortality. Association was measured in terms of prevalence ratio (PR) and beta coefficient and respective 95% CIs, crude and adjusted for variables that obtained a value of p&lt;0.20 in the crude model (maternal age, education and parity).

Results
The overall unplanned pregnancies rate was 65%, of which 40.5% were mistimed pregnancies and 24.5% unwanted pregnancies. Unplanned and mistimed pregnancies were significantly associated with insufficient birth weight [adjusted prevalence ratio (aPR)=2.14; 95% CI 1.01 to 4.56 and aPR=2.43; 95% CI 1.09 to 5.39, respectively] and unwanted pregnancies were significantly associated with preterm birth (aPR=3.49; 95% CI 1.01 to 12.11). Furthermore, adjusted analysis showed that birth weight and gestational age were lower in unplanned, mistimed and unwanted pregnancies.

Conclusions
Unplanned pregnancy was associated with lower birth weight and shorter gestational age of newborns. These data collected in a public hospital in a developing country may have significant implications today. If pregnancy intention is not included as a neonatal risk factor, insufficient birth weight and preterm birth could increase because a higher proportion of births will be unplanned.
Enforcing the Digital Markets Act: institutional choices, compliance, and antitrust
Authors: Crémer Jacques , Dinielli David , Heidhues Paul , Kimmelman Gene , Monti Giorgio , Podszun Rupprecht , Schnitzer Monika , Scott Morton Fiona , de Streel Alexandre 
Published: March 2023

Abstract
This article discusses how the European Commission can achieve the goal of effectively implementing the Digital Markets Act. Based on legal and economic reasoning, we highlight the important role of the gatekeeper’s compliance report, and discuss how to incentivize gatekeepers to write useful reports. In addition, we develop recommendations regarding the internal organization of the Commission, the prioritization of cases, and how to effectively use the concurrent enforcement powers of the Digital Markets Act and Article 102 of the TFEU. We illustrate the principles we develop using four different EU antitrust cases. Furthermore, we discuss coordination between the Commission and National Competition Authorities and the need to already develop an independent evaluation process for the Digital Markets Act.
Construction of a Zinc Oxide Nanorod-Modified Coated Wire Electrode for Potentiometric Determination of Levocetirizine Dihydrochloride in Its Pure and Combined Form
Authors: Nashed Dania , Noureldin Imad , Alhaj Sakur Amir 
Published: March 2023

Abstract

Background
Coated wire electrodes (CWEs) are considered the most effective and selective type of ion- selective electrodes because of the electroactive materials which are used in surface modification.

Objective
This study aims to construct the first potentiometric method for analysis of levocetirizine (LVZ) in its combination form with montelukast (MON) drug.

Methods
A novel potentiometric sensor which consists of a silver wire coated with zinc oxide (ZnO) nanorod modified with a polymeric membrane (combining β-cyclodextrin and tetraphenyl borate, and plasticized with di-butyl phthalate) was constructed for the determination of LVZ·2HCl in its pure form and its combination dosage form.

Results
The fabricated sensor exhibited a linearity range of 5 × 10−6–1 × 10−2 mol/L with a Nernstian slope 57.88 mV/decade over the pH range 2–4.5. The effect of temperature on the constructed sensor was studied and it was found that the electrode worked effectively over 10–50°C. The electrode showed a fast response time and the lifetime of the electrode was found to be 72 days without significant change in the Nernstian slope value. The selectivity of the electrode toward LVZ was estimated in the presence of some obstructive ions.

Conclusion
The method was validated according to International Council for Harmonisation of Technical Requirments for Registration of Pharmaceuticals for Human Use (ICH) rules and applied to the determination of LVZ in its pure and combined pharmaceutical dosage forms.

Highlights
This article introduces the synthesis of the first coated wire electrode modified with zinc oxide (ZnO) nanorods for the determination of the drug levocetirizine. The results demonstrate the ability of electrochemical methods to analyze drugs in combination. The presented method excels over the other analytical methods in terms of sensitivity, selectivity, and simplicity.
Design of phase II oncology trials evaluating combinations of experimental agents
Authors: Sharon Elad , Foster Jared C 
Published: March 2023

Abstract
We consider the design of phase II trials evaluating combinations of experimental therapies. In the modern era, many immunotherapy and targeted therapy regimens are being developed as combination regimens, including combinations consisting only of experimental agents. In some clinical or drug development scenarios, it may be difficult to isolate the effect of the individual agents composing a combination of this type, which makes the evaluation of the combination challenging. One such scenario arises when none of the agents making up the experimental combination have demonstrated single-agent activity in the clinical setting of interest. One solution to this problem is to use a randomized comparative trial in which the combination of interest is compared with 1 or both of its component agents, but some modifications to more traditional randomized comparative phase II trials must be made because all arms in such a trial would be experimental. In this manuscript, we present sensible modifications to randomized phase II trial designs that can be used in 2 common drug development scenarios of this type and provide a detailed discussion of the practical aspects of designing these trials. We also include 2 worked examples to further illustrate how to design such a trial.
Is Australia a Model for the UK? A Critical Assessment of Parallels of Cruelty in Refugee Externalization Policies
Authors: Matera Margherita , Tubakovic Tamara , Murray Philomena 
Published: March 2023

Abstract
For several years, Australia has been regarded by some politicians and observers in Europe as a model for hard-line policies towards refugees. At the same time, Australia’s implementation of refugee externalization measures has been subject to considerable scholarly attention and critique. Although the Australian approach has featured prominently in political debates in several European states, this article analyses the implications of a possible adoption of the Australian offshore detention approach for refugee policy-making in the UK, and the consequences this will have for the integrity of the international refugee protection regime. The article considers how states might influence each other’s policies—both directly and indirectly—by focusing on a case study of offshore detention and processing with regard to Australia’s influence on—and similarity to—the UK, to the extent that we observe policy parallels, as the article brings to light substantial policy convergence of detrimental practice of these two countries.
Multilevel emulation for stochastic computer models with application to large offshore wind farms
Authors: Kennedy Jack C , Henderson Daniel A , Wilson Kevin J 
Published: March 2023

Abstract
Renewable energy projects, such as large offshore wind farms, are critical to achieving low-emission targets set by governments. Stochastic computer models allow us to explore future scenarios to aid decision making while considering the most relevant uncertainties. Complex stochastic computer models can be prohibitively slow, and thus an emulator may be constructed and deployed to allow for efficient computation. We present a novel heteroscedastic Gaussian Process emulator that exploits cheap approximations to a stochastic offshore wind farm simulator. We also conduct a probabilistic sensitivity analysis to understand the influence of key parameters in the wind farm model, which will help us to plan a probability elicitation in the future.