bluuebunny/crossref_metadata_2025 huggingface dataset:
An Update on the Healthy Soldier Effect in U.S. Veterans
Authors: Sullivan-Baca Erin , Rehman Rizwana , Haneef Zulfi
Published: June 2022

Introduction

The healthy soldier effect (HSE) describes a phenomenon of enduring health and lower mortality among veterans due in part to initial screening procedures and health care access. Although early data were supportive of a broad HSE among former military members, more recent investigations have suggested a possible attenuation of the effect with older age. The present study aimed to provide an update of the HSE using an expansive Veterans Health Administration (VHA)–wide sample with a particular focus on age and sex effects.

Materials and Methods

Mortality data for veterans within the VHA were obtained from the VHA Support Service Center program office and compared to mortality data from the general U.S. population spanning FY2014 to the second quarter of FY2020. The standardized mortality ratio (SMR) was calculated for the overall sample and for age- and sex-specific cohorts. Mortality rate ratios were also calculated and compared across sexes.

Results

Lower SMRs were observed in veterans compared to the general U.S. population (SMR 0.866). This effect was most prominent in younger and very old veterans, although a higher mortality was seen in the 55- to 64-year age cohort (SMR 1.371 for males and 1.074 for females). The HSE in females was lower than that in males in the <55-year age group but became higher in older cohorts.

Conclusions

This is the largest investigation to date examining the HSE in U.S. veterans and includes younger veterans from more recent military eras. Higher mortality among the 55- to 74-year age groups merits further investigation, as does the relatively higher mortality among older female veterans. Our findings have implications for the provision of health care and preventative care to these veterans most at risk for higher mortality.
Asteroseismology of the dip structure in period-spacings of rapidly rotating γ Doradus stars caused by the coupling between core and envelope oscillations
Authors: Tokuno Takato , Takata Masao
Published: June 2022

Recent asteroseismic observations by the Kepler space mission have revealed the dip fine structure in the period-spacing versus period diagram of rapidly rotating γ Doradus stars. Following the successful reproduction of the dip structure by numerical calculations in previous studies, we present in this paper the physical mechanism of how the dip is formed as a result of the interaction between the gravito-inertial waves in the radiative envelope and the pure inertial waves in the convective core. We analytically describe the wave solutions in both of the radiative envelope and the convective core, and match them at the interface to construct an eigenmode. We have found from the analysis the following points: the dip structure is mainly controlled by a parameter that has an inverse correlation with Brunt–Väisälä frequency at the interface; the depth and the width of the dip is shallower and larger, respectively, as the parameter gets large; the shape of the dip can be approximated by the Lorentzian function; the period at the central position of the dip is equal to or slightly smaller than that of the involved pure inertial mode in the convective core. We have also understood based on the evolutionary models of main-sequence stars that the parameter is inversely correlated with the chemical composition gradient at the convective-core boundary. The dip structure thus would provide information about the poorly-understood physical processes, such as diffusion, convective overshooting and rotational mixing, around the boundary between the convective core and the radiative envelope.
Kink oscillations in a coronal loop arcade with finite plasma-β: effect of oblique propagation
Authors: Lopin I
Published: June 2022

Kink oscillations of a curved coronal slab with finite plasma-β, simulating a loop arcade, are examined. Perpendicular propagation, i.e. propagation along the arcade axis (ky > 0) is taken into account. Two surface modes, labelled as faster and slower mode, are found to exist in the model. In the zero-β limit, the faster mode is a vertically polarized kink mode and the slower mode produces bending motions polarized along the arcade axis, provided $k_y^{-1}$ is of the order of or larger than the slab thickness a. Otherwise, if $k_y^{-1}$ is much less than a, the faster mode results in periodic displacement of a loop arcade along its axis and the slower mode has mixed properties. The phase speeds of both modes are very similar when $k_y^{-1}\sim a$, and they tend to the external and internal Alfvén speeds when ky → 0. As the internal plasma-β becomes finite and grows, the phase speed of the faster mode increases and that of the slower mode decreases. When βi > 0, these modes are a superposition of vertical kink motions and those that are oriented along the arcade axis, both supplemented with the significant cross-averaged density perturbations. It seems promising to use the obtained results for interpreting quasi-periodic pulsations, in terms of kink oscillations of flaring high-β loops, provided the developed theory is applicable to the torroidal single loop model when choosing an appropriate ky.
Atmosphere loss by aerial bursts
Authors: Trierweiler Isabella L , Schlichting Hilke E
Published: June 2022

We present a simple analytic description of atmospheric mass loss by aerial bursts and demonstrate that mass loss from aerial bursts becomes significant when the maximum impactor size that leads to an aerial burst rather than a ground explosion, ro, is larger than the minimum impactor size needed to achieve atmospheric loss, rmin. For vertical trajectories, which give the most stringent limit, this condition is approximately satisfied when ρo/ρi ≳ 0.4v, which implies atmospheric densities need to be comparable to impactor densities for impactor velocities that are a few times the escape velocity of the planet. The range of impactor radii resulting in aerial burst-induced mass loss, ro–rmin, increases with the ratio of the atmosphere to the impactor density and with the trajectory angle of the impactor. The range of impactor radii that result in aerial burst-induced mass loss and the atmospheric mass lost is larger in adiabatic atmospheres than in isothermal atmospheres of equivalent total mass, scale height, and atmospheric surface density. Our results imply that aerial bursts are not expected to significantly contribute to the atmospheric mass loss history of Earth, but are expected to play an important role for planets and exoplanets similar to Neptune with significant atmospheres. For Neptune-like atmospheres, the atmospheric mass ejected per impactor mass by aerial bursts is comparable to that lost by ground explosions, which implies that, for impactors following a Dohnanyi size distribution, overall loss by aerial bursts is expected to exceed that by ground explosions by a factor of (rground/raerial)0.5.
An efficient method for simulating light curves of cosmological microlensing and caustic crossing events
Authors: Meena Ashish Kumar , Arad Ofir , Zitrin Adi
Published: June 2022

A new window to observing individual stars and other small sources at cosmological distances was opened recently, with the detection of several caustic-crossing events in galaxy cluster fields. Many more such events are expected soon from dedicated campaigns with the Hubble Space Telescope and the James Webb Space Telescope. These events can not only teach us about the lensed sources themselves, such as individual high-redshift stars, star clusters, or accretion discs, but through their light curves they also hold information about the point-mass function of the lens, and thus, potentially, the composition of dark matter. We present here a simple method for simulating light curves of such events, i.e. the change in apparent magnitude of the source as it sweeps over the net of caustics generated by microlenses embedded around the critical region of the lens. The method is recursive and so any reasonably sized small source can be accommodated, down to sub-solar scales, in principle. We compare the method, which we dub Adaptive Boundary Method, with other common methods such as simple inverse ray shooting, and demonstrate that it is significantly more efficient and accurate in the small-source and high-magnification regime of interest. A python version of the code is made publicly available in an open-source fashion for simulating future events.
Classifying Kepler light curves for 12 000 A and F stars using supervised feature-based machine learning
Authors: Barbara Nicholas H , Bedding Timothy R , Fulcher Ben D , Murphy Simon J , Van Reeth Timothy
Published: June 2022

With the availability of large-scale surveys like Kepler and TESS, there is a pressing need for automated methods to classify light curves according to known classes of variable stars. We introduce a new algorithm for classifying light curves that compares 7000 time-series features to find those that most effectively classify a given set of light curves. We apply our method to Kepler light curves for stars with effective temperatures in the range 6500–10 000 K. We show that the sample can be meaningfully represented in an interpretable 5D feature space that separates seven major classes of light curves (δ Scuti stars, γ Doradus stars, RR Lyrae stars, rotational variables, contact eclipsing binaries, detached eclipsing binaries, and non-variables). We achieve a balanced classification accuracy of 82 per cent on an independent test set of Kepler stars using a Gaussian mixture model classifier. We use our method to classify 12 000 Kepler light curves from Quarter 9 and provide a catalogue of the results. We further outline a confidence heuristic based on probability density to search our catalogue and extract candidate lists of correctly classified variable stars.
Low-luminosity type IIP supermnovae: SN 2005cs and SN 2020cxd as very low-energy iron core-collapse explosions
Authors: Kozyreva Alexandra , Janka Hans-Thomas , Kresse Daniel , Taubenberger Stefan , Baklanov Petr
Published: June 2022

SN 2020cxd is a representative of the family of low-energy, underluminous Type IIP supernovae (SNe), whose observations and analysis were recently reported by Yang et al. (2021). Here, we re-evaluate the observational data for the diagnostic SN properties by employing the hydrodynamic explosion model of a 9 M⊙ red supergiant progenitor with an iron core and a pre-collapse mass of 8.75 M⊙. The explosion of the star was obtained by the neutrino-driven mechanism in a fully self-consistent simulation in three dimensions (3D). Multiband light curves and photospheric velocities for the plateau phase are computed with the one-dimensional radiation-hydrodynamics code STELLA, applied to the spherically averaged 3D explosion model as well as sphericized radial profiles in different directions of the 3D model. We find that the overall evolution of the bolometric light curve, duration of the plateau phase, and basic properties of the multiband emission can be well reproduced by our SN model with its explosion energy of only 0.7 × 1050 erg and an ejecta mass of 7.4 M⊙. These values are considerably lower than the previously reported numbers, but they are compatible with those needed to explain the fundamental observational properties of the prototype low-luminosity SN 2005cs. Because of the good compatibility of our photospheric velocities with line velocities determined for SN 2005cs, we conclude that the line velocities of SN 2020cxd are probably overestimated by up to a factor of about 3. The evolution of the line velocities of SN 2005cs compared to photospheric velocities in different explosion directions might point to intrinsic asymmetries in the SN ejecta.
Incidence of new carotid plaques in rheumatoid arthritis patients: 6-Year prospective results of the TOMORROW study
Authors: Anno Shohei , Okano Tadashi , Mamoto Kenji , Sugioka Yuko , Tada Masahiro , Inui Kentaro , Koike Tatsuya , Nakamura Hiroaki
Published: June 2022

Objectives

The purpose of this study was to evaluate the new incidence of carotid plaques in rheumatoid arthritis (RA) patients over a 6-year prospective follow-up and to assess the risk factors.

Methods

This is a 10-year prospective cohort study that included 208 RA patients and 205 age- and gender-matched controls. Ultrasound assessment of the bilateral carotid arteries was performed in 2011 and 2017.

Results

There were no differences in the incidence of new carotid atherosclerotic plaques over 6 years between the two groups (35.5% vs. 37.0%, respectively; p = .936). The mean Disease Activity Score 28-C-reactive protein over 6 years in RA patients was 2.73 ± 0.95. Multiple logistic regression analysis showed that RA was not a risk factor for new carotid atherosclerotic plaques (odds ratios, 0.708; 95% confidence interval, 0.348–1.440; p = .340). An average glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques (odds ratios, 8.54; 95% confidence interval, 1.641–44.455; p = .011).

Conclusions

Incidence of new carotid atherosclerotic plaques was similar between well-controlled disease activity RA patients and control subjects. A mean glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques.
The evolution of stomatal traits along the trajectory toward C4 photosynthesis
Authors: Zhao Yong-Yao , Lyu Mingju Amy , Miao FenFen , Chen Genyun , Zhu Xin-Guang
Published: June 2022

C4 photosynthesis optimizes plant carbon and water relations, allowing high photosynthetic rates with low stomatal conductance. Stomata have long been considered a part of the C4 syndrome. However, it remains unclear how stomatal traits evolved along the path from C3 to C4. Here, we examined stomata in the Flaveria genus, a model used for C4 evolutionary study. Comparative, transgenic, and semi-in vitro experiments were performed to study the molecular basis that underlies the changes of stomatal traits in C4 evolution. The evolution from C3 to C4 species is accompanied by a gradual rather than an abrupt change in stomatal traits. The initial change appears near the Type I intermediate stage. Co-evolution of the photosynthetic pathway and stomatal traits is supported. On the road to C4, stomata tend to be fewer in number but larger in size and stomatal density dominates changes in anatomical maximum stomatal conductance (gsmax). Reduction of FSTOMAGEN expression underlies decreased gsmax in Flaveria and likely occurs in other C4 lineages. Decreased gsmax contributes to the increase in intrinsic water-use efficiency in C4 evolution. This work highlights the stomatal traits in the current C4 evolutionary model. Our study provides insights into the pattern, mechanism, and role of stomatal evolution along the road toward C4.
A First Estimate of the Annual Prevalence of Basivertebral Nerve Ablation Candidates in a Spine Clinic
Authors: Sherwood David , Miller Scott , Epps Adam , Gill Benjamin , Zhivotenko Oksana , Khan Samir , Swenson Theodora , Gardner James , Roehmer Christian , Martin Dann , Kennedy David “D J” , Modic Michael , Schneider Byron J
Published: June 2022

Background

Emerging literature supports the use of basivertebral nerve ablation (BVNA) for a specific cohort of patients with chronic low back pain and Type 1 or Type 2 Modic changes from vertebral levels L3–S1. The early literature warrants further evaluation. Studies establishing the efficacy of BVNA use highly selective patient criteria.

Objective

Provide a first estimate of the prevalence of BVNA candidates in a spine clinic over a year using the foundational studies patient selection criteria?

Methods

A retrospective review of four fellowhsip trained spine physiatrists patient encounters at a large academic medical center using relevant ICD-10 codes to isolate chronic low back pain without radiating symptoms from January 1, 2019 to January 1, 2020. Charts were then reviewed by a team of physicians for exclusionary criteria from the foundational studies which have demonstrated benefit from BVNA. MRI’s from qualifying charts which did not meet exclusionary criteria were then independently reviewed by four physician for localization and characterization of Modic changes.

Results

The relevant diagnostic codes query yielded 338 unique patient records. Based on exclusionary criteria or lack of imaging availability, 318 charts were eliminated. The remaining 20 charts qualified for imaging review. There were 11 charts in which there was 100% agreement between all reviewers regarding the presence and either Type 1 or Type 2 Modic changes between vertebral levels L3 to S1. Accordingly, the prevalence of eligibility for BVNA was 3% (11/338, 95% CI 1–5%).

Conclusion

The population which may benefit from BVNA is small. Our study demonstrated that over a year, the prevalence for BVNA candidacy using the foundational studies criteria was 3% (95% CI 1% – 5%). While physicians may be tempted to use less stringent selection criteria in practice, upon doing so they cannot cite the foundational studies as evidence for the outcomes they expect to achieve. Those outcomes will require more studies which formally assess the benefits of BVNA when selection criteria are relaxed.
Optimal Fiscal Policy in a Model with Uninsurable Idiosyncratic Income Risk
Authors: Dyrda Sebastian , Pedroni Marcelo
Published: June 2022

We study optimal fiscal policy in a standard incomplete-markets model with uninsurable idiosyncratic income risk, where a Ramsey planner chooses time-varying paths of proportional capital and labour income taxes, lump-sum transfers (or taxes), and government debt. We find that (1) short-run capital income taxes are effective in providing redistribution since the tax base is relatively unequal and inelastic; (2) an increasing pattern of labour income taxes over time mitigates intertemporal distortions from capital income taxes; (3) the optimal policy increases overall transfers, calibrated initially to the US welfare system, by roughly $50\%$; (4) two-thirds of the welfare gains come from redistribution and the remaining third come mostly from insurance; and (5) redistribution also leads to a more efficient allocation of labour via wealth effects on labour supply—lower productivity households can afford to work relatively less.
Metabolomics mapping changed after olanzapine therapy in drug-naive schizophrenia patients—the significant impact of gene polymorphisms
Authors: Karahalil Bensu , Elkama Aylin , Ak Mehmet , Nemutlu Emirhan
Published: June 2022

Oxidative stress may contribute to the development of schizophrenia and antipsychotics used in schizophrenia treatment may also cause oxidative stress. Gene polymorphisms on antioxidant and repair enzymes are responsible for individual variations and may change the efficacy of olanzapine treatment among schizophrenia patients. In our study, we assessed oxidative stress-related metabolite changes due to genetic polymorphisms on first diagnosed-schizophrenia patients treated with olanzapine. Blood samples (n = 30 patients) were taken before treatment (T1), after 10 ± 1 days (T2), and after 3 ± 1 months (T3). T1 served as control for T2 and T3, since it is advantageous to perform on same patient to evaluate the impact of olanzapine only. GSTs (GSTM1, GSTT1, and GSTP1) and OGG1 gene polymorphisms were analyzed by polymerase chain reaction. Changes in metabolites were detected with metabolomics profiling by gas chromatography–mass spectrometry according to each genotype before and after treatment. Multivariate analysis showed that metabolomics profiles differed after olanzapine treatment regardless gene polymorphisms. Tryptophan could be a biomarker in response to olanzapine treatment since its levels were increased after treatment. GSTM1 gene polymorphism caused significant changes in some metabolites after treatment. Urea, palmitic acid, and caprylic acid levels increased and alanine levels decreased in patients with GSTM1 null genotypes after olanzapine. In future, targeted metabolomics with these prominent metabolites and assessing gene expressions of GSTs will be beneficial to understand the mechanism of action.
10Performance, Theatre, and Drama
Authors: Simpson Hannah
Published: June 2022

The first section of this review, ‘Staging Reality’, reads two monographs that grapple with large-scale thinking about how theatre and performance engage with various ideas of ‘reality’: Lindsay Brandon Hunter’s exploration of performing ‘the real’ in theatre, television, and alternative-reality gaming in Playing Real: Mimesis, Media, and Mischief, and Bess Rowen’s theorizing of ‘affective stage directions’ in The Lines Between the Lines: How Stage Directions Affect Embodiment. The second section, ‘Politics and/of Performance’, reviews two books with an explicit interest in the political as well as aesthetic dimensions of performance: Tiziana Morosetti and Osita Okagbue’s edited volume The Palgrave Handbook of Theatre and Race, and Jon Venn’s Madness in Contemporary British Theatre: Resistances and Representations. The final section shifts to monographs that structure their enquiry around a specific figure: the playwright Jez Butterworth, in the case of Sean McEvoy’s Class, Culture and Tragedy in the Plays of Jez Butterworth, and the biblical figure of Salomé, in the case of Megan Girdwood’s Modernism and the Choreographic Imagination: Salome’s Dance after 1890.
A Novel Method of Steroid Delivery to Improve the Efficacy of Intralesional Injection in Keloid Treatment
Authors: Cho Mi Yeon , Song Ahreum , Chung Kee Yang , Roh Mi Ryung
Published: June 2022

BACKGROUND

Keloids are a chronic disease and cause pain, pruritus, and limitation of motion. Intralesional corticosteroid injection is the first-line treatment, but its effects can be limited, even with repeated injections.

OBJECTIVE

To investigate the efficacy and safety of a tunneling method of corticosteroid injection compared with conventional intralesional injection.

MATERIALS AND METHODS

A retrospective review was conducted of keloid patients treated with intralesional corticosteroid injection by conventional and tunneling methods.

RESULTS

A total of 119 cases of keloid were included in the study. Among 78 patients treated with 20 mg/mL triamcinolone, the Investigators' Global Assessment effectiveness score and Observer Scar Assessment Scale (OSAS) score were significantly higher in the tunneling group than the conventional group at 1 month. At 6 months, the tunneling group showed significantly higher effectiveness in the OSAS score than the conventional group. In the tunneling group, the interval between treatments was significantly longer than in the conventional group. The occurrence of side effects was lower in the tunneling method group than in the conventional method group.

CONCLUSION

This study reveals the benefits of the tunneling method over the conventional method for therapeutic effect and side effects in keloid treatment.
Bioelectrical Impedance Analysis (BIA)- Derived Phase Angle in Children and Adolescents: A Systematic Review
Authors: Ballarin Giada , Valerio Giuliana , Alicante Paola , Di Vincenzo Olivia , Scalfi Luca
Published: June 2022

Phase angle (PhA), a directly-measured bioelectrical impedance analysis variable, is suggested to be a proxy of body cell mass as well as extracellular/intracellular water ratio, and is related to cellular integrity and functions. The aim of this systematic review was to evaluate PhA in healthy youths in relation to sex, age, weight status, physical fitness, and sports activities. A systematic literature search (preferred reporting items for systematic reviews and meta-analyses criteria) until January 2022 was performed using PubMed, Embase, Scopus, and Web of Science regarding studies on PhA in healthy children and adolescents 4–18 years of age. Quality was assessed according to the National Institute of Health. After removing duplicates and studies not fulfilling the inclusion criteria, 22 cross-sectional and 1 longitudinal were considered appropriate. As for quality, 14 articles were rated fair and 9 good. Ten studies found that PhA increases with age: the increase was more marked after puberty, whereas changes in younger subjects are by far less defined. A clear sex difference was found in adolescents, likely due to pubertal development. Limited evidence suggests that PhA increases in participants with very high BMI. Limited data were reported on physically active youths without convincing findings. Positive associations of PhA with physical fitness and fat-free mass were found in few studies. In conclusion, partial and limited evidence suggests that changes in PhA over the first 2 decades of life reflect modification in body composition and fat-free mass composition. Further studies are needed for confirming PhA as a relevant marker of nutritional status in youths.
Growing the Next Generation of Trauma Surgeon Scientists – Reflections on 20 Years of Research Investment
Authors: Callcut Rachael A. , Dixon Rachel , Smith Jason W. , Zarzaur Ben ,   the EAST Research-Scholarship Committee
Published: June 2022

Introduction

The EAST mission includes fostering research and providing career development opportunities. EAST has awarded for 20 years a Research Scholarship to a promising young investigator. The Research mentorship efforts were expanded 5 yrs ago with the INVEST-C Hack-a-thon. INVEST-C provides an intensive, short-term engagement to propel junior faculty toward establishing research independence. This study investigates the impact of these programs on academic productivity.

Methods

Pubmed records, NIH Reporter data, and SCOPUS h-index was acquired for all scholarship [SCH] awardees from 2002-2021 (n = 20) and all INVEST-C [INV] participants (2017-2020, n = 19). Current type of practice, total number of funding awards, and timing of first award were ascertained. INVEST-C participants were also surveyed on an annual basis to track their progress. Medians (IQR) are reported and compared (ANOVA).

Results

Median publications (PUB) of SCH awardees was 56 [IQR 33-88], h-index 16 (12-21), and 25% with > = 1 NIH grant since their SCH. Amongst the last 10 awardees with a minimum of 2 yrs from SCH, 40% have received a NIH award compared with a mean NIH funding rate of 18.5% over the same time period. For those remaining in academics (90% SCH), PUB were higher for those >5 yrs (66, 51-115) vs. <5 yrs from their SCH (33, 22-59, p = 0.05), but there was no difference in h-index (16, IQR 14-25, vs 15, 9-19, p = NS). Comparing the most recent 5 yrs of SCH to INV group, there was no difference in academic productivity as measured by total PUB (SCH 33, IQR 22-59 vs INV 34, IQR 18-44, p = 0.7) or h-index (INV 9, 5-14, p = 0.1). However, no attendee held research funding prior to INV, but 31.6% (6/19) have subsequently acquired > = 1 funding award (11 non-NIH, 1 NIH) in the short interval since participation.

Conclusion

Investments in research activities have translated to significant extramural funding. Those in the last 5 yrs have been particularly fruitful with INV participants already achieving equal median academic productivity to SCH recipients.

Level of Evidence

Level III, Epidemiologic, Cohort
Lipidome- and genome-wide study to understand sex differences in circulatory lipids
Authors: Tabassum Rubina , Ruotsalainen Sanni , Ottensmann Linda , Gerl Mathias J. , Klose Christian , Tukiainen Taru , Pirinen Matti , Simons Kai , Widén Elisabeth , Ripatti Samuli
Published: June 2022

Despite well-recognized difference in the atherosclerotic cardiovascular disease (ASCVD) risk between men and women, sex differences in risk factors and sex specific mechanisms in the pathophysiology of ASCVD remain poorly understood. Lipid metabolism plays a central role in the development of ASCVD. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in ASCVD and aid in precise risk assessment. Thus, we examined sex differences in plasma levels of 179 lipid species from 7,266 participants and performed sex-stratified genome-wide association studies (GWAS) to evaluate contribution of genetic factors in sex differences. We sought for replication using independent data from 2,045 participants. Significant sex differences in levels of 141 lipid species were observed (P<7.0×10−4). Interestingly, 121 lipid species showed significant age-sex interactions with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids and glycerides were higher in 45-50-year-old men compared with women of same age, but the sex-differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex stratified GWAS which suggests that common genetic variants do not have a major role in sex differences in lipidome. In conclusion, our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism, highlighting need for sex- and age-specific prevention strategies.
The cost of the COVID-19 pandemic vs the cost-effectiveness of mitigation strategies in the EU/UK/EEA and OECD countries: a systematic review
Authors: Vardavas Constantine , Zisis Konstantinos , Nikitara Katerina , Lagou Ioanna , Aslanoglou Katerina , Athanasakis Kostas , Phalkey Revati , Leonardi-Bee Jo , Fernandez Esteve , Condell Orla , Lamb Favelle , Sandmann Frank , Pharris Anastasia , Deogan Charlotte , Suk Jonathan E.
Published: June 2022

Objectives

COVID-19 poses a threat of loss of life, economic instability, and social disruption. We conducted a systematic review of published economic analyses to assess the direct and indirect costs of the SARS-CoV-2 pandemic, and to contrast these with the costs and the cost-benefit of public health surveillance, preparedness, and response measures in averting and/or responding to SARS-CoV-2 pandemic.

Setting

A systematic literature review was conducted to identify peer-reviewed articles estimating the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions in EU/EEA/UK and OECD countries, published from the 1st of January 2020 through 22nd April 2021 in Ovid Medline and EMBASE. The cost-effectiveness of interventions was assessed through a dominance ranking matrix approach. All cost data were adjusted to the 2021 Euro, with interventions compared with the null.

Primary and secondary outcome measures

Direct and indirect costs for SARS-CoV-2 and preparedness and/or response or cost-benefit and cost-effectiveness were measured.

Results

We included data from 41 economic studies. Ten studies evaluated the cost of COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness, and response measures. Overall, the economic burden of SARS-CoV-2 was found to be substantial for both the general population and within specific population subgroups. Community screening, bed provision policies, investing in personal protective equipment and vaccination strategies were cost-effective, in most cases due to the representative economic value of below acceptable cost-effectiveness thresholds. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented.

Conclusions

SARS-CoV-2 is associated with substantial economic costs to healthcare systems, payers, and societies, both short term and long term, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic.
Impact of Adverse Drug Reactions in the outcomes of Tuberculosis Treatment
Authors: Sant’Anna Flávia M. , Araújo-Pereira Mariana , Schmaltz Carolina A. S. , Arriaga María B. , Andrade Bruno B. , Rolla Valeria C.
Published: June 2022

Adverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on treatment outcomes. A prospective cohort study of persons with tuberculosis at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate probability ADR-free time. A logistic regression model was performed to identify independent associations with unfavorable outcomes. 550 patients were enrolled and 35.1% were people living with HIV (PLHIV). ADR occurred in 78.6% of participants and was associated with favorable outcomes. Smokers (OR:2.32;95%CI:1.34-3.99) and illicit drug users (OR:2.02;95%CI:1.15-3.55) exhibited higher risk of unfavorable outcome. PLHIV more frequently experienced grade 3/4-ADR, specially “liver and biliary system disorders”. Lower CD4 counts were associated with hepatotoxicity (p=0.03). Male sex, low schooling, smoking and illicit-drug use are independent risk factors for unfavorable outcomes, as well alcohol abuse and previous ART in PLHIV. ADR increases the odds of favorable outcomes, although it is more severe in PLHIV and related to a higher risk of hepatotoxicity.
U.S. CDC support to international SARS-CoV-2 seroprevalence surveys, May 2020–February 2022
Authors: Hamida Amen Ben , Charles Myrna , Murrill Christopher , Henao Olga , Gallagher Kathleen
Published: June 2022

SARS-CoV-2 seroprevalence surveys provide critical information to assess the burden of COVID-19, describe population immunity, and guide public health strategies. Early in the pandemic, most of these surveys were conducted within high-income countries, leaving significant knowledge gaps in low-and middle-income (LMI) countries. To address this gap, the U.S. Centers for Disease Control and Prevention (CDC) is supporting serosurveys internationally.

We conducted a descriptive analysis of international serosurveys supported by CDC during May 12, 2020–February 28, 2022, using an internal tracker including data on the type of assistance provided, study design, population surveyed, laboratory testing performed, and status of implementation. Since the beginning of the pandemic, CDC has supported 72 serosurveys (77 serosurvey rounds) in 35 LMI countries by providing technical assistance (TA) on epidemiologic, statistical, and laboratory methods, financial assistance (FA), or both. Among these serosurvey rounds, the majority (61%) received both TA and FA from CDC, 30% received TA only, 3% received only FA, and 5% were part of informal reviews. Fifty-four percent of these serosurveys target the general population, 13% sample pregnant women, 7% sample healthcare workers, 7% sample other special populations (internally displaced persons, patients, students, and people living with HIV), and 18% assess multiple or other populations. These studies are in different stages of implementation, ranging from protocol development to dissemination of results. They are conducted under the leadership of local governments, who have ownership over the data, in collaboration with international partners. Thirty-four surveys rounds have completed data collection.

CDC TA and FA of SARS-CoV-2 seroprevalence surveys will enhance the knowledge of the COVID-19 pandemic in almost three dozen LMI countries. Support for these surveys should account for current limitations with interpreting results, focusing efforts on prospective cohorts, identifying, and forecasting disease patterns over time, and helping understand antibody kinetics and correlates of protection.
Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529) dominance: A Danish nationwide study
Authors: Nielsen Katrine Finderup , Moustsen-Helms Ida Rask , Schelde Astrid Blicher , Gram Mie Agermose , Emborg Hanne-Dorthe , Nielsen Jens , Hansen Christian Holm , Andersen Michael Asger , Meaidi Marianna , Wohlfahrt Jan , Valentiner-Branth Palle
Published: June 2022

Introduction

Individuals with a prior severe acute respiratory corona virus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, that is, in individuals with prior SARS-CoV-2 infection, during periods with different dominant SARS-CoV-2 variants.

Methods

A nationwide cohort study design including all individuals with a confirmed SARS-CoV-2 infection, who were alive and residing in Denmark between 1 January 2020 and 31 January 2022 were used. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, Coronavirus Disease 2019 (COVID-19) vaccination, age, sex, comorbidity, staying at hospital and region of affiliation. The study population included were individuals with prior SARS-CoV-2 infection. Crude and adjusted estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using Poisson and Cox regression models, respectively. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference.

Findings

The study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%) and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 85% (95% CI: 37% to 97%) at 104 days or more after vaccination during the Alpha period, 88% (95% CI: 81% to 92%) 14-43 days after vaccination during the Delta period and 60% (95% CI: 58% to 62%) 14-43 days after vaccination during the Omicron period. Waning immunity was observed, and was most pronounced during the Omicron period.

Interpretation

This study shows that, in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination for all three variant periods. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods.
Obesity and longevity: The retrospective longitudinal analysis of international data
Authors: Liapin G. , Vlassov V.
Published: June 2022

Objectives

Due to the economic growth at the end of the 20th century people in low-income countries live longer, but still spend on food most of their income, and suffer from the low food quality. These countries, as well as affluent countries demonstrate rising prevalence of obesity, which is a risk factor for bad health and increased mortality. The interplay of longevity and obesity at different levels of economic development is not clear.

Design

We used World Bank, International Monetary Fund, and Global Burden of Disease project data on population size, longevity, prevalence of obesity, and income as Gross domestic product per capita adjusted to purchasing power in international dollars.

Results

After we stratified countries by income, we found that there is a long-term increase in life expectancy with an increase in the prevalence of obesity in countries of all income levels. There is a higher prevalence of obesity in poor countries than in the affluent countries at the equal life expectancy.

Conclusions

The economic growth in all countries lead to increase in length of life and is associated with the increase of obesity prevalence. In poor countries the access to food and the food quality is limited as well as customs of consumption are different. It leads to the higher prevalence of overweight and obesity at similar level of length of life. It may be the cause of the slower progress in life expectancy.
Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and rewires the microenvironment toward an immune-suppressive state
Authors: Tang Yan , Kwiatkowski David J. , Henske Elizabeth P.
Published: June 2022

mTORC1 regulates cell metabolism to enable cell proliferation, and is hyperactive in multiple cancer types1, 2. Here, we performed integrative analysis of single cell transcriptomic profiling, paired T cell receptor (TCR) sequencing, and spatial transcriptomic profiling on Tuberous Sclerosis Complex (TSC) associated tumors with mTORC1 hyperactivity, and identified a stem-like tumor cell state (SLS) linked to T cell dysfunction via tumor-modulated immunosuppressive macrophages. Rapamycin and its derivatives (rapalogs) are the primary treatments for TSC tumors, and the stem-like tumor cells showed rapamycin resistance in vitro, reminiscent of the cytostatic effects of these drugs in patients. The pro-angiogenic factor midkine (MDK) was highly expressed by the SLS population, and associated with enrichment of endothelial cells in SLS-dominant samples. Inhibition of MDK showed synergistic benefit with rapamycin in reducing the growth of TSC cell lines in vitro and in vivo. In aggregate, this study suggests an autocrine rapamycin resistance mechanism and a paracrine tumor survival mechanism via immune suppression adopted by the stem-like state tumor cells with mTORC1 hyperactivity. We also provide a comprehensive resource to advance the understanding of TSC and potentially other mTORC1-hyperactive tumors.
Mapping-by-sequencing reveals genomic regions associated with seed quality parameters in Brassica napus
Authors: Schilbert Hanna Marie , Pucker Boas , Ries David , Viehöver Prisca , Micic Zeljko , Dreyer Felix , Beckmann Katrin , Wittkop Benjamin , Weisshaar Bernd , Holtgräwe Daniela
Published: June 2022

Rapeseed (Brassica napus L.) is an important oil crop and harbours the potential to serve as a highly productive source of protein. This protein exhibits an excellent amino acid composition and has a high nutritional value for humans. Seed protein content (SPC) and seed oil content (SOC) are two complex quantitative and polygenic traits which are negatively correlated and assumed to be controlled by additive and epistatic effects. A reduction of seed glucosinolate (GSL) content is desired as GSLs cause a stringent and bitter taste. The goal here was the identification of genomic intervals relevant for seed GSL content and SPC/SOC. Mapping-by-sequencing (MBS) revealed 30 and 15 new and known genomic intervals associated with seed GSL content and SPC/SOC, respectively. Within these intervals we identified known but also so far unknown putatively causal genes and sequence variants. A 4 bp insertion in the MYB28 homolog on C09 shows a significant correlation with a reduction in seed GSL content. This study provides insights into the genetic architecture and potential mechanisms underlying seed quality traits, which will enhance future breeding approaches in B. napus.
Evolutionary unpredictability in cancer model system
Authors: Chattopadhyay Subhayan , Karlsson Jenny , Mañas Adriana , Kanzaki Ryu , Fredlund Elina , Murphy Andrew J. , Morton Christopher L. , Andersson Natalie , Woolard Mary A. , Hansson Karin , Radke Katarzyna , Davidhoff Andrew M. , Mohlin Sofie , Pietras Kristian , Bexell Daniel , Gisselsson David
Published: June 2022

Despite the advent of personalized medicine, it is still difficult to predict how a cancer develops over time at the level of the individual patient or even in cancer model systems which begs the question whether certain aspects of cancer can ever be predicted or if there is an inherent unpredictability in cancer, similar to other complex biological systems, We demonstrate by a combination of agent-based mathematical modelling and analysis of data from patient-derived xenograft systems from multiple cancer types that certain conditions may invoke chaotic fluctuations in the clonal landscape of cancer cells. Our findings indicate that under those conditions, the cancer genome behaves as a complex dynamic system, making its long-term evolution inherently unpredictable.
Genome-wide analyses of vocabulary size in infancy and toddlerhood: associations with Attention-Deficit/Hyperactivity Disorder and cognition-related traits
Authors: Verhoef Ellen , Allegrini Andrea G. , Jansen Philip R. , Lange Katherine , Wang Carol A. , Morgan Angela T. , Ahluwalia Tarunveer S. , Symeonides Christos ,   EAGLE working group, Eising Else , Franken Marie-Christine , Hypponen Elina , Mansell Toby , Olislagers Mitchell , Omerovic Emina , Rimfeld Kaili , Schlag Fenja , Selzam Saskia , Shapland Chin Yang , Tiemeier Henning , Whitehouse Andrew J.O. , Saffery Richard , Bønnelykke Klaus , Reilly Sheena , Pennell Craig E. , Wake Melissa , Cecil Charlotte A.M. , Plomin Robert , Fisher Simon E. , St Pourcain Beate
Published: June 2022

Background

The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors, although mechanisms are not well understood. Here, we performed a meta-genome-wide association study within the EAGLE consortium and investigated polygenic overlap with later-life traits, including Attention-Deficit/Hyperactivity Disorder (ADHD) and cognition.

Methods

We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months) and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated Single-Nucleotide Polymorphism heritability (SNP-h2), genetic correlations (rg) and modelled underlying genetic factor structures with multivariate models.

Results

Contributions of common genetic variation to early-life vocabulary were modest (SNP-h2: 0.08(SE=0.01) to 0.24(SE=0.03)) and multi-factorial. Genetic overlap between infant expressive and toddler receptive vocabulary was near zero (rg=0.07(SE=0.10)), although both measures were genetically related to toddler expressive vocabulary (rg=0.69(SE=0.14) and rg=0.67(SE=0.16), respectively). Consistently, polygenic association patterns with later-life traits differed: Genetic links with cognition emerged only in toddlerhood (e.g. toddler receptive vocabulary and intelligence: rg=0.36(SE=0.12)), despite comparable study power for infant measures. Furthermore, increased polygenic ADHD risk was associated with larger infant expressive vocabulary (rg=0.23(SE=0.08)), as confirmed by ADHD-symptom-based follow-up analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC-rg=0.54(SE=0.26)). Genetic relationships with toddler receptive vocabulary were, however, opposite (ALSPAC-rg=-0.74(SE=0.23)), highlighting developmental changes in genetic architectures.

Conclusions

Multiple genetic components contribute to early-life vocabulary development, shaping polygenic association patterns with later-life ADHD symptoms and cognition.