bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling the imposed magnetospheres of Mars-like exoplanets: star–planet interactions and atmospheric losses
Authors: Basak Arnab , Nandy Dibyendu
Published: January 2021

Based on 3D compressible magnetohydrodynamic simulations, we explore the interactions between the magnetized wind from a solar-like star and a Mars-like planet – with a gravitionally stratified atmosphere – that is either non-magnetized or hosts a weak intrinsic dipolar field. The primary mechanism for the induction of a magnetosphere around a non-magnetized conducting planet is the pile-up of stellar magnetic fields in the day-side region. The magnetopause stand-off distance decreases as the strength of the planetary dipole field is lowered and saturates to a minimum value for the case of a planet with no magnetic field. Global features such as bow shock, magnetosheath, magnetotail, and strong current sheets are observed in the imposed magnetosphere. We explore variations in atmospheric mass loss rates for different stellar wind strengths to understand the impact of stellar magnetic activity and plasma winds – and their evolution – on (exo)planetary habitability. In order to simulate a case analogous to the present-day Mars, a planet without atmosphere is considered. Our simulations are found to be in good agreement with observational data from Mars Global Surveyor and Mars Atmosphere and Volatile EvolutioN missions and is expected to complement observations from the Emirates (Hope) Mars Mission, China's Tianwen-1 and NASA's Mars 2020 Perseverance mission.
Kozai–Lidov oscillations triggered by a tilt instability of detached circumplanetary discs
Authors: Martin Rebecca G , Zhu Zhaohuan , Armitage Philip J , Yang Chao-Chin , Baehr Hans
Published: January 2021

Circumplanetary discs can be linearly unstable to the growth of disc tilt in the tidal potential of the star–planet system. We use 3D hydrodynamical simulations to characterize the disc conditions needed for instability, together with its long-term evolution. Tilt growth occurs for disc aspect ratios, evaluated near the disc outer edge, of H/r ≳ 0.05, with a weak dependence on viscosity in the wave-like regime of warp propagation. Lower mass giant planets are more likely to have circumplanetary discs that satisfy the conditions for instability. We show that the tilt instability can excite the inclination to above the threshold where the circumplanetary disc becomes unstable to Kozai–Lidov (KL) oscillations. Dissipation in the KL unstable regime caps further tilt growth, but the disc experiences large oscillations in both inclination and eccentricity. Planetary accretion occurs in episodic accretion events. We discuss implications of the joint tilt–KL instability for the detectability of circumplanetary discs, for the obliquity evolution of forming giant planets, and for the formation of satellite systems.
Structural basis of diversity and homodimerization specificity of zinc-finger-associated domains in Drosophila
Authors: Bonchuk Artem , Boyko Konstantin , Fedotova Anna , Nikolaeva Alena , Lushchekina Sofya , Khrustaleva Anastasia , Popov Vladimir , Georgiev Pavel
Published: January 2021

In arthropods, zinc finger-associated domains (ZADs) are found at the N-termini of many DNA-binding proteins with tandem arrays of Cys2-His2 zinc fingers (ZAD-C2H2 proteins). ZAD-C2H2 proteins undergo fast evolutionary lineage-specific expansion and functional diversification. Here, we show that all ZADs from Drosophila melanogaster form homodimers, but only certain ZADs with high homology can also heterodimerize. CG2712, for example, is unable to heterodimerize with its paralog, the previously characterized insulator protein Zw5, with which it shares 46% homology. We obtained a crystal structure of CG2712 protein's ZAD domain that, in spite of a low sequence homology, has similar spatial organization with the only known ZAD structure (from Grauzone protein). Steric clashes prevented the formation of heterodimers between Grauzone and CG2712 ZADs. Using detailed structural analysis, site-directed mutagenesis, and molecular dynamics simulations, we demonstrated that rapid evolutionary acquisition of interaction specificity was mediated by the more energy-favorable formation of homodimers in comparison to heterodimers, and that this specificity was achieved by multiple amino acid substitutions resulting in the formation or breaking of stabilizing interactions. We speculate that specific homodimerization of ZAD-C2H2 proteins is important for their architectural role in genome organization.
Bacteria have numerous distinctive groups of phage–plasmids with conserved phage and variable plasmid gene repertoires
Authors: Pfeifer Eugen , Moura de Sousa Jorge A , Touchon Marie , Rocha Eduardo P C
Published: January 2021

Plasmids and temperate phages are key contributors to bacterial evolution. They are usually regarded as very distinct. However, some elements, termed phage–plasmids, are known to be both plasmids and phages, e.g. P1, N15 or SSU5. The number, distribution, relatedness and characteristics of these phage–plasmids are poorly known. Here, we screened for these elements among ca. 2500 phages and 12000 plasmids and identified 780 phage–plasmids across very diverse bacterial phyla. We grouped 92% of them by similarity of gene repertoires to eight defined groups and 18 other broader communities of elements. The existence of these large groups suggests that phage–plasmids are ancient. Their gene repertoires are large, the average element is larger than an average phage or plasmid, and they include slightly more homologs to phages than to plasmids. We analyzed the pangenomes and the genetic organization of each group of phage–plasmids and found the key phage genes to be conserved and co-localized within distinct groups, whereas genes with homologs in plasmids are much more variable and include most accessory genes. Phage–plasmids are a sizeable fraction of the sequenced plasmids (∼7%) and phages (∼5%), and could have key roles in bridging the genetic divide between phages and other mobile genetic elements.
Experts’ Perceptions of and Suggestions for Cigar Warning Label Messages and Pictorials
Authors: Wackowski Olivia A , Jeong Michelle , Schroth Kevin R J , Rashid Mariam , Delnevo Cristine D
Published: January 2021

Introduction

Warning labels can be effective tools to inform the public about tobacco risks. However, tobacco warning research has been largely cigarette-centric. This formative study explores potential directions for improving the current warnings for cigars.

Aims and Methods

Between June and August 2019, we conducted interviews with 10 experts about the current cigar warning statements and requirements, the inclusion of pictorials in cigar warnings, and legal issues. Additionally, experts viewed and discussed concept images to pair with existing warning statements, including realistic photographic images and symbolic images (eg, icons, caution symbols).

Results

Experts agreed that cigar warnings should be strengthened (eg, by increasing their size and use of pictorials) to better leverage their potential impact and maintain warning parity with cigarettes. However, perceived challenges exist given the wide variety of cigar products, product terminology, and use patterns. Experts agreed that photographic pictorials of health effects are likely to be more salient, informative, and effective for behavior change than symbolic ones, but may be vulnerable to legal challenges. Symbolic images used in warnings may obtain attention in a less “controversial” way, but may be considered less serious and “factually accurate,” increasing legal risks. Experts indicate that cigar educational campaigns can complement warnings and address additional themes, especially aimed at youth, including exposure to chemicals and flavorings and misperceptions that cigars are “natural.”

Conclusions

Additional consumer research is needed to examine the potential public health impact of improving cigar warnings and to support regulatory efforts.

Implications

This study provides feedback from tobacco control experts about the importance of cigar warning labels and directions for future research and improvements. Experts support increasing the size of cigar warnings and adopting pictorials to improve cigar warning impact and maintain warning parity with cigarettes. Experts agreed that photographic pictorials of health effects are likely to be more salient and effective for behavior change than symbolic ones. Given legal challenges, experts discussed potentially prioritizing warning improvements for those cigars used most frequently as cigarette alternatives and by youth. Overall, more cigar warning research is needed to support regulatory efforts.
Winter zooplankton dynamics in the English Channel and southern North Sea: trends and drivers from 1991 to 2013
Authors: Dudeck Tim , Rohlf Norbert , Möllmann Christian , Hufnagl Marc
Published: January 2021

Winter has long been regarded as a period of minor importance in marine zooplankton ecology with static, low concentrations and growth rates of organisms. Yet, there is growing evidence that winter conditions influence spring bloom strength. With rising water temperatures, growing importance of fish larvae survival during winter and the lack of data to parameterize ecosystem models for this period, research focus shifted on winter zooplankton ecology. To enable looking into past changes in winter zooplankton ecology, we established a new winter zooplankton time series based on samples collected in the eastern English Channel and southern North Sea by the International Herring Larvae Survey since 1988. Four areas of the study region were identified containing different congregations of zooplankton. Overall, zooplankton size decreased while total zooplankton abundance increased, reaching its maximum in 2011. Zooplankton abundance dynamics were mainly related to temperature, chlorophyll a concentration and North Atlantic Oscillation index. Depth and Atlantic water inflow strongly influenced zooplankton size. Increased chlorophyll a concentration and high abundances of small copepods indicated bottom-up controlled secondary production since 2010 and a possible winter bloom in 2011. Based on the analysed parameters, no relation between herring larvae abundance and zooplankton or environmental drivers was determined.
Insights into the mechanisms of transport and regulation of the arabidopsis high-affinity K+ transporter HAK51
Authors: Ródenas Reyes , Ragel Paula , Nieves-Cordones Manuel , Martínez-Martínez Almudena , Amo Jesús , Lara Alberto , Martínez Vicente , Quintero Francisco J , Pardo Jose M , Rubio Francisco
Published: January 2021

The high-affinity K+ transporter HAK5 from Arabidopsis (Arabidopsis thaliana) is essential for K+ acquisition and plant growth at low micromolar K+ concentrations. Despite its functional relevance in plant nutrition, information about functional domains of HAK5 is scarce. Its activity is enhanced by phosphorylation via the AtCIPK23/AtCBL1-9 complex. Based on the recently published three-dimensionalstructure of the bacterial ortholog KimA from Bacillus subtilis, we have modeled AtHAK5 and, by a mutational approach, identified residues G67, Y70, G71, D72, D201, and E312 as essential for transporter function. According to the structural model, residues D72, D201, and E312 may bind K+, whereas residues G67, Y70, and G71 may shape the selective filter for K+, which resembles that of K+shaker-like channels. In addition, we show that phosphorylation of residue S35 by AtCIPK23 is required for reaching maximal transport activity. Serial deletions of the AtHAK5 C-terminus disclosed the presence of an autoinhibitory domain located between residues 571 and 633 together with an AtCIPK23-dependent activation domain downstream of position 633. Presumably, autoinhibition of AtHAK5 is counteracted by phosphorylation of S35 by AtCIPK23. Our results provide a molecular model for K+ transport and describe CIPK-CBL-mediated regulation of plant HAK transporters.
Plasma membrane phylloquinone biosynthesis in nonphotosynthetic parasitic plants
Authors: Gu Xi , Chen Ing-Gin , Harding Scott A , Nyamdari Batbayar , Ortega Maria A , Clermont Kristen , Westwood James H , Tsai Chung-Jui
Published: January 2021

Nonphotosynthetic holoparasites exploit flexible targeting of phylloquinone biosynthesis to facilitate plasma membrane redox signaling. Phylloquinone is a lipophilic naphthoquinone found predominantly in chloroplasts and best known for its function in photosystem I electron transport and disulfide bridge formation of photosystem II subunits. Phylloquinone has also been detected in plasma membrane (PM) preparations of heterotrophic tissues with potential transmembrane redox function, but the molecular basis for this noncanonical pathway is unknown. Here, we provide evidence of PM phylloquinone biosynthesis in a nonphotosynthetic holoparasite Phelipanche aegyptiaca. A nonphotosynthetic and nonplastidial role for phylloquinone is supported by transcription of phylloquinone biosynthetic genes during seed germination and haustorium development, by PM-localization of alternative terminal enzymes, and by detection of phylloquinone in germinated seeds. Comparative gene network analysis with photosynthetically competent parasites revealed a bias of P. aegyptiaca phylloquinone genes toward coexpression with oxidoreductases involved in PM electron transport. Genes encoding the PM phylloquinone pathway are also present in several photoautotrophic taxa of Asterids, suggesting an ancient origin of multifunctionality. Our findings suggest that nonphotosynthetic holoparasites exploit alternative targeting of phylloquinone for transmembrane redox signaling associated with parasitism.
Consumer acceptance and willingness to pay for cow housing systems in eight European countries
Authors: Waldrop Megan E , Roosen Jutta
Published: January 2021

Free walk housing systems aim to address major animal health issues for dairy cows and support higher animal welfare. The purpose of this study is to estimate consumer acceptance of different housing systems and willingness to pay (WTP) for milk from tie-stall, cubicle, compost-bedded, and artificial floor housing systems in addition to attitudes toward animal welfare. Focus groups were held to identify the pertinent concepts for an online quantitative survey conducted in eight European countries. A discrete choice experiment was included for estimating WTP. Consumers are found to care about animal welfare and grazing. Results indicate consumers like the compost-bedded system the best followed by the artificial floor system; however, no positive WTP for these systems was found. Consumers seem to find the current labeling rules regarding organic production and grazing sufficiently informative. The results can help producers make more informed investment and marketing decisions regarding cow husbandry.
Defining the optimal disease duration of early diffuse systemic sclerosis for clinical trial design
Authors: Domsic Robyn T , Gao Shiyao , Laffoon Maureen , Wisniewski Steven , Zhang Yuqing , Steen Virginia , Lafyatis Robert , Medsger Thomas A
Published: January 2021

Objectives

Clinical trials in early diffuse cutaneous systemic sclerosis (SSc) using the modified Rodnan skin score (mRSS) as the primary outcome measure have most often been negative. We wanted to assess how the definition of disease onset (first SSc manifestation vs first non-Raynaud manifestation) and varying lengths of disease duration at trial entry as an inclusion criteria functioned. Our objective was to optimize trial inclusion criteria

Methods

We used the prospective, observational University of Pittsburgh Scleroderma Cohort to identify early diffuse SSc patients first evaluated between 1980 and 2015. All had <3 years from first SSc (n = 481) or first non-Raynaud manifestation (n = 514) and three or more mRSS scores. We used descriptive, survival and group-based trajectory analyses to compare the different definitions of disease onset and disease duration as inclusion criteria for clinical trials.

Results

There was no appreciable difference between using first SSc manifestation compared with first non-Raynaud manifestation as the definition of disease onset. Compared with other disease durations, <18 months of disease had >70% of patients fitting into trajectories with worsening cutaneous disease over 6 months of follow-up. Longer disease durations demonstrated the majority of patients with trajectories showing an improvement in mRSS (regression to the mean) over 6 months.

Conclusions

Regardless of whether the first SSc or first non-Raynaud manifestation is used to define disease onset, duration of <18 months at enrolment is preferable. A longer disease duration criterion more frequently results in regression to the mean of the mRSS score, and likely contributes to negative trial outcomes.
Post-translational modifications in T cells in systemic erythematosus lupus
Authors: Yang Fan , Lin Jin , Chen Weiqian
Published: January 2021

Systemic erythematosus lupus (SLE) is a classic autoimmune disease characterized by multiple autoantibodies and immune-mediated tissue damage. The aetiology of this disease is still unclear. A new drug, belimumab, which acts against the B-lymphocyte stimulator (BLyS), can effectively improve the condition of SLE patients, but it cannot resolve all SLE symptoms. The discovery of novel, precise therapeutic targets is urgently needed. It is well known that abnormal T-cell function is one of the most crucial factors contributing to the pathogenesis of SLE. Protein post-translational modifications (PTMs), including phosphorylation, glycosylation, acetylation, methylation, ubiquitination and SUMOylation have been emphasized for their roles in activating protein activity, maintaining structural stability, regulating protein–protein interactions and mediating signalling pathways, in addition to other biological functions. Summarizing the latest data in this area, this review focuses on the potential roles of diverse PTMs in regulating T-cell function and signalling pathways in SLE pathogenesis, with the goal of identifying new targets for SLE therapy.
Is Cohort Representativeness Passé? Poststratified Associations of Lifestyle Risk Factors with Mortality in the UK Biobank
Authors: Stamatakis Emmanuel , Owen Katherine B. , Shepherd Leah , Drayton Bradley , Hamer Mark , Bauman Adrian E.
Published: January 2021

Background:

The UK Biobank (UKB) has been used widely to examine associations between lifestyle risk factors and mortality outcomes. It is unknown whether the extremely low UKB response rate (5.5%) and lack of representativeness materially affects the magnitude and direction of effect estimates.

Methods:

We used poststratification to match the UKB sample to the target population in terms of sociodemographic characteristics and prevalence of lifestyle risk factors (physical inactivity, alcohol intake, smoking, and poor diet). We compared unweighted and poststratified associations between each lifestyle risk factor and a lifestyle index score with all-cause, cardiovascular disease (CVD), and cancer mortality. We also calculated the unweighted to poststratified ratio of HR (RHR) and 95% confidence interval as a marker of effect-size difference.

Results:

Of 371,974 UKB participants with no missing data, 302,009 had no history of CVD or cancer, corresponding to 3,298,958 person years of follow-up. Protective associations between alcohol use and CVD mortality observed in the unweighted UKB were substantially altered after poststratification, for example, from a hazard ratio (HR) of 0.63 (0.45–0.87) unweighted to 0.99 (0.65–1.50) poststratified for drinking ≥5 times/week versus never drinking. The magnitude of the poststratified all-cause mortality hazard ratio comparing least healthy with healthiest tertile of lifestyle risk factor index was 9% higher (95% confidence interval: 4%, 14%) than the unweighted estimates.

Conclusions:

Lack of representativeness may distort the associations of alcohol with CVD mortality, and may underestimate health hazards among those with cumulatively the least healthy lifestyles.
Health Service Utilization Patterns Among Medicaid-Insured Adults With Intellectual and Developmental Disabilities
Authors: Lauer Emily , Lindgren Scott , Momany Elizabeth , Cope Tara , Royer Julie , Cogan Lindsay , McDermott Suzanne , Armour Brian
Published: January 2021

Limited existing evidence suggests that adults with intellectual and developmental disabilities (IDD) experience substantial disparities in numerous areas of health care, including quality ambulatory care. A multistate cohort of adults with IDD was analyzed for patterns of inpatient admissions and emergency department utilization. Utilization was higher (inpatient [RR = 3.2], emergency department visits [RR = 2.6]) for adults with IDD, particularly for ambulatory care–sensitive conditions (eg, urinary tract [RR = 6.6] and respiratory infections [RRs = 5.5-24.7]), and psychiatric conditions (RRs = 5.8-15). Findings underscore the importance of access to ambulatory care skilled in IDD-related needs to recognize and treat ambulatory care–sensitive conditions and to manage chronic medical and mental health conditions.
Increased resistance to fibrinolysis activation in patients with coronavirus disease 2019: a case series
Authors: Duque Patricia , Chasco-Ganuza Maite , Burgos-Santamaria Alba , Terradillos Estrella
Published: January 2021

We describe seven critically ill and seven noncritically ill patients with coronavirus disease 2019 infection. Two viscoelastic assays were performed with ClotPro technology, activated by extrinsic system test and recombinant tissue plasminogen activator challenge test. Coagulation profile presents a marked hypercoagulability with increased resistance to fibrinolysis, reflected by tissue plasminogen activator test. Our pathological observations show that the hypercoagulative status described in these patients is, at least partially, secondary to fibrinolysis shutdown.
Association of mutation in PTPN14 gene and gingival fibromatosis with distinctive facies: a novel finding in whole exome sequencing
Authors: Cogulu Ozgur , Mojarrab Neda , Simsir Ozguc S. , Durmaz Asude , Aykut Ayca , Cogulu Dilsah
Published: January 2021

Gingival fibromatosis with distinctive facies presents a rare clinical picture. It is characterized by gingival fibromatosis in conjunction with some craniofacial dysmorphic features such as relative macrocephaly, bushy eyebrows, synophrys, hypertelorism, downslanting palpebral fissures, flattened nasal bridge, hypoplastic nares, cupid-bow mouth and a high palate. Autosomal recessive inheritance has been suggested. However, to date, no causative gene has been reported. Herein, we report a case presenting with the typical findings of this rare genetic syndrome. A homozygous c.1855C>T (p.Gln619Ter) mutation in the PTPN14 gene was identified.
Health Care Satisfaction in Relation to Gender Identity
Authors: Ferrucci Katarina A. , Walubita Tubanji , Beccia Ariel L. , Ding Eric Y. , Jesdale Bill M. , Lapane Kate L. , Streed Carl G.
Published: January 2021

Background:

Health care satisfaction is a key component of patient-centered care. Prior research on transgender populations has been based on convenience samples, and/or grouped all gender minorities into a single category.

Objective:

The objective of this study was to quantify differences in health care satisfaction among transgender men, transgender women, gender nonconforming, and cisgender adults in a diverse multistate sample.

Research Design:

Cross-sectional analysis of 2014–2018 Behavioral Risk Factor Surveillance System data from 20 states, using multivariable logistic models.

Subjects:

We identified 167,468 transgender men, transgender women, gender-nonconforming people, cisgender women, and cisgender men and compared past year health care satisfaction across these groups.

Results:

Transgender men and women had the highest prevalence of being “not at all satisfied” with the health care they received (14.6% and 8.6%, respectively), and gender-nonconforming people had the lowest prevalence of being “very satisfied” with their health care (55.7%). After adjustment for sociodemographic characteristics, transgender men were more likely to report being “not at all satisfied” with health care than cisgender men (odds ratio: 4.45, 95% confidence interval: 1.72–11.5) and cisgender women (odds ratio: 3.40, 95% confidence interval: 1.31–8.80).

Conclusions:

Findings indicate that transgender and gender-nonconforming adults report considerably less health care satisfaction relative to their cisgender peers. Interventions to address factors driving these differences are needed.
Estimated Lifetime HIV–Related Medical Costs in the United States
Authors: Bingham Adrienna , Shrestha Ram K. , Khurana Nidhi , Jacobson Evin U. , Farnham Paul G.
Published: January 2021

Background

Lifetime cost estimates are a useful tool in measuring the economic burden of HIV in the United States. Previous estimation methods need to be updated, given improving antiretroviral therapy regimens and updated costs.

Methods

We used an updated version of the agent-based model progression and transmission of HIV (PATH) 3.0 to reflect current regimens and costs. We simulated a cohort of those infected in 2015 until the last person had died to track the lifetime costs for treatment of HIV, including HIV health care utilization costs (inpatient, outpatient, opportunistic infection prophylaxis, non-HIV medication, and emergency department), opportunistic infection treatment costs, and testing costs. We assumed a median per-person diagnosis delay of 3 years and a 3% base monthly probability of dropout from care for a base-case scenario. Additionally, we modeled a most favorable scenario (median diagnosis delay of 1 year and 1% base dropout rate) and a least favorable scenario (median diagnosis delay of 5 years and 5% base dropout rate).

Results

We estimated an average lifetime HIV-related medical cost for a person with HIV of $420,285 (2019 US$) discounted (3%) and $1,079,999 undiscounted for a median 3-year diagnosis delay and 3% base dropout rate. Our discounted cost estimate was $490,045 in our most favorable scenario and $326,411 in our least favorable scenario.

Conclusions

Lifetime per-person HIV-related medical costs depend on the time from infection to diagnosis and the likelihood of dropping out of care. Our results, which are similar to previous studies, reflect updated antiretroviral therapy regimens and costs for HIV treatment.
Estimates of the Prevalence and Incidence of Genital Herpes, United States, 2018
Authors: Spicknall Ian H. , Flagg Elaine W. , Torrone Elizabeth A.
Published: January 2021

Background

Although there are more recent estimate of genital herpes prevalence, incidence estimates in the United States (US) have not been updated since 2008.

Methods

We estimated genital herpes prevalence and incidence for 2018 among adults aged 18 to 49 years. We estimated prevalence using 2015–2018 National Health and Nutrition Examination Survey herpes simplex virus type 2 (HSV-2) seroprevalence data among the noninstitutionalized civilian population and extrapolated this prevalence to the full US population using 2018 American Community Survey data. We estimated incidence using 2011 to 2018 National Health and Nutrition Examination Survey HSV-2 data as inputs to a simple mathematical model. We used Monte Carlo simulation to generate 10,000 input parameter sets for age and sex subpopulations and summarized our estimates by their median; uncertainty intervals for these estimates are characterized by their first (Q1) and third (Q3) quartiles. We conducted sensitivity analyses investigating the impact of HSV type 1 (HSV-1) infection on estimates of genital herpes burden.

Results

In 2018, there were an estimated 18.6 (Q1 = 18.1, Q3 = 19.0) million prevalent and 572,000 (Q1 = 479,000, Q3 = 673,000) incident genital herpes infections among 18- to 49-year-olds. Women accounted for two thirds of prevalent infections with an estimated 12.1 (Q1 = 11.9, Q3 = 12.5) million infections. Incidence was highest among 18- to 24-year-olds with an estimated 242,000 (Q1 = 210,000, Q3 = 274,000) infections. Sensitivity analyses indicated that HSV-1 could be responsible for millions more prevalent genital herpes infections, and tens of thousands of additional incident genital herpes infections, depending on the percentage of HSV-1 infections that are genital.

Discussion

Genital herpes is a common sexually transmitted disease in the United States. Future research to understand the burden of genital infections attributable to HSV-1 would refine estimates of genital herpes burden.
The Estimated Lifetime Medical Cost of Diseases Attributable to Human Papillomavirus Infections Acquired in 2018
Authors: Chesson Harrell W. , Laprise Jean-François , Brisson Marc , Martin Dave , Ekwueme Donatus U. , Markowitz Lauri E.
Published: January 2021

Introduction

We estimated the lifetime medical costs of diagnosed cases of diseases attributable to human papillomavirus (HPV) infections acquired in 2018.

Methods

We adapted an existing mathematical model of HPV transmission and associated diseases to estimate the lifetime number of diagnosed cases of disease (genital warts; cervical intraepithelial neoplasia; and cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers) attributable to HPV infections that were acquired in 2018. For each of these outcomes, we multiplied the estimated number of cases by the estimated lifetime medical cost per case obtained from previous studies. We estimated the costs of recurrent respiratory papillomatosis in a separate calculation. Future costs were discounted at 3% annually.

Results

The estimated discounted lifetime medical cost of diseases attributable to HPV infections acquired in 2018 among people aged 15 to 59 years was $774 million (in 2019 US dollars), of which approximately half was accounted for by infections in those aged 15 to 24 years. Human papillomavirus infections in women accounted for approximately 90% of the lifetime number of diagnosed cases of disease and 70% of the lifetime cost attributable to HPV infections acquired in 2018 among those aged 15 to 59 years.

Conclusions

We estimated the lifetime medical costs of diseases attributable to HPV infections acquired in 2018 to be $774 million. This estimate is lower than previous estimates, likely due to the impact of HPV vaccination. The lifetime cost of disease attributable to incident HPV infections is expected to decrease further over time as HPV vaccination coverage increases.
The Estimated Direct Lifetime Medical Costs of Sexually Transmitted Infections Acquired in the United States in 2018
Authors: Chesson Harrell W. , Spicknall Ian H. , Bingham Adrienna , Brisson Marc , Eppink Samuel T. , Farnham Paul G. , Kreisel Kristen M. , Kumar Sagar , Laprise Jean-François , Peterman Thomas A. , Roberts Henry , Gift Thomas L.
Published: January 2021

Background

We estimated the lifetime medical costs attributable to sexually transmitted infections (STIs) acquired in 2018, including sexually acquired human immunodeficiency virus (HIV).

Methods

We estimated the lifetime medical costs of infections acquired in 2018 in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), hepatitis B, and HIV. We limited our analysis to lifetime medical costs incurred for treatment of STIs and for treatment of related sequelae; we did not include other costs, such as STI prevention. For each STI, except HPV, we calculated the lifetime medical cost by multiplying the estimated number of incident infections in 2018 by the estimated lifetime cost per infection. For HPV, we calculated the lifetime cost based on the projected lifetime incidence of health outcomes attributed to HPV infections acquired in 2018. Future costs were discounted at 3% annually.

Results

Incident STIs in 2018 imposed an estimated $15.9 billion (25th–75th percentile: $14.9–16.9 billion) in discounted, lifetime direct medical costs (2019 US dollars). Most of this cost was due to sexually acquired HIV ($13.7 billion) and HPV ($0.8 billion). STIs in women accounted for about one fourth of the cost of incident STIs when including HIV, but about three fourths when excluding HIV. STIs among 15- to 24-year-olds accounted for $4.2 billion (26%) of the cost of incident STIs.

Conclusions

Incident STIs continue to impose a considerable lifetime medical cost burden in the United States. These results can inform health economic analyses to promote the use of cost-effective STI prevention interventions to reduce this burden.
Overexpression of the TRIM24 E3 Ubiquitin Ligase is Linked to Genetic Instability and Predicts Unfavorable Prognosis in Prostate Cancer
Authors: Höflmayer Doris , Fraune Christoph , Hube-Magg Claudia , Simon Ronald , Schroeder Cornelia , Büscheck Franziska , Möller Katharina , Dum David , Weidemann Sören , Wittmer Corinna , Schlomm Thorsten , Huland Hartwig , Heinzer Hans , Graefen Markus , Haese Alexander , Sauter Guido , Burandt Eike , Clauditz Till S. , Steurer Stefan , Minner Sarah , Wilczak Waldemar , Polonski Adam
Published: January 2021

Tripartite motif containing 24 (TRIM24) is a multifunctional protein involved in p53 degradation, chromatin binding, and transcriptional modulation of nuclear receptors. Emerging research has revealed that upregulation of TRIM24 in numerous tumor types is linked to poor prognosis, attributing an important role to TRIM24 in tumor biology. In order to better understand the role of TRIM24 in prostate cancer, we analyzed its immunohistochemical expression on a tissue microarray containing >17,000 prostate cancer specimens. TRIM24 immunostaining was detectable in 61% of 15,321 interpretable cancers, including low expression in 46% and high expression in 15% of cases. TRIM24 upregulation was associated with high Gleason grade, advanced pathologic tumor stage, lymph node metastasis, higher preoperative prostate-specific antigen level, increased cell proliferation as well as increased genomic instability, and predicted prognosis independent of clinicopathologic parameters available at the time of the initial biopsy (all P<0.0001). TRIM24 upregulation provides additional prognostic information in prostate cancer, particularly in patients with low Gleason grade tumors who may be eligible for active surveillance strategies, suggesting promising potential for TRIM24 in the routine diagnostic work-up of these patients.
Development, Assessment, and Outcomes of a Community-Based Model of Antiretroviral Care in Western Kenya Through a Cluster-Randomized Control Trial
Authors: Goodrich Suzanne , Siika Abraham , Mwangi Ann , Nyambura Monicah , Naanyu Violet , Yiannoutsos Constantin , Spira Thomas , Bateganya Moses , Toroitich-Ruto Cathy , Otieno-Nyunya Boaz , Wools-Kaloustian Kara
Published: January 2021

Objective:

To develop and assess an alternative care model using community-based groups for people living with HIV and facilitate by lay personnel.

Methods:

Geographic locations in the Academic Model Providing Access to Healthcare Kitale clinic catchment were randomized to standard of care versus a community-based care group (ART Co-op). Adults stable on antiretroviral therapy and virally suppressed were eligible. Research Assistant–led ART Co-ops met in the community every 3 months. Participants were seen in the HIV clinic only if referred. CD4 count and viral load were measured in clinic at enrollment and after 12 months. Retention, viral suppression, and clinic utilization were compared between groups using χ2, Fisher exact, and Wilcoxon rank sum tests.

Results:

At 12 months, there were no significant differences in mean CD4 count or viral load suppression. There was a significant difference in patient retention in assigned study group between the intervention and control group (81.6% vs 98.6%; P < 0.001), with a number of intervention patients withdrawing because of stigma, relocation, pregnancy, and work conflicts. All participants, however, were retained in an HIV care program for the study duration. The median number of clinic visits was lower for the intervention group than that for the control group (0 vs 3; P < 0.001).

Conclusions:

Individuals retained in a community-based HIV care model had clinical outcomes equivalent to those receiving clinic-based care. This innovative model of HIV care addresses the problems of insufficient health care personnel and patient retention barriers, including time, distance, and cost to attend clinic, and has the potential for wider implementation.
Surgical Outcomes, Technical Performance, and Surgery Burden of Robotic Total Gastrectomy for Locally Advanced Gastric Cancer
Authors: Chen Qi-Yue , Zhong Qing , Liu Zhi-Yu , Li Ping , Wang Jia-Bin , Lin Jian-Xian , Lu Jun , Cao Long-Long , Lin Mi , Tu Ru-Hong , Huang Ze-Ning , Lin Ju-Li , Zheng Hua-Long , Lin Guang-Tan , Zheng Chao-Hui , Huang Chang-Ming , Xie Jian-Wei
Published: January 2021

Objective:

To compare the short-term outcomes, surgery burden, and technical performance of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) for gastric cancer (GC).

Summary of Background Data:

The impact of robotic systems on total gastrectomy remains obscure.

Methods:

This prospective study included 50 patients with advanced proximal GC underwent RTG combined with spleen-preserving splenic hilar lymphadenectomy between March 2018 and February 2020. Patients who underwent LTG in the FUGES-002, http://links.lww.com/SLA/C929 study were enrolled to compare the outcomes between RTG and LTG.

Results:

After propensity score matching, 48 patients in the RTG group and 96 patients in the LTG group were included in the analysis. The RTG group had a lower volume of intraoperative blood loss than the LTG group (38.7 vs 66.4 mL, P = 0.042). Significantly more extraperigastric lymph nodes were retrieved in the RTG group than in the LTG group (20.2 vs 17.5, P = 0.039). The average number of errors was lower in the RTG group than in the LTG group (43.2 vs 53.8 times/case, P < 0.001). The RTG group had a higher technical skill score (30.2 vs 28.4, P < 0.001) and a lower surgery task load index (33.2 vs 39.8, P < 0.001) than the LTG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.6% vs 16.7%, P = 0.748).

Conclusions:

In complex total gastrectomy for GC, compared with traditional laparoscopic surgery, robotic surgery provides a technically superior operative environment and reduces surgeon workload at high-volume specialized institutions.
Tonic Pupil Following COVID-19
Authors: Gopal Madhumita , Ambika Selvakumar , Padmalakshmi Krishnakumar
Published: January 2021

A 37-year-old patient presented to our emergency department with sudden onset decreased vision with a history of being treated for COVID 19 3 weeks earlier. On examination, she was found to have a tonic right pupil, which was confirmed with a dilute pilocarpine test. As tonic pupils are known to be caused by neurotropic viruses and our current understanding of the SARS-CoV-2 is that it does affect the nervous system, we feel that the tonic pupil in our patient may be secondary to COVID 19.
Grounding cognition: heterarchical control mechanisms in biology
Authors: Bechtel William , Bich Leonardo
Published: January 2021

We advance an account that grounds cognition, specifically decision-making, in an activity all organisms as autonomous systems must perform to keep themselves viable—controlling their production mechanisms. Production mechanisms, as we characterize them, perform activities such as procuring resources from their environment, putting these resources to use to construct and repair the organism's body and moving through the environment. Given the variable nature of the environment and the continual degradation of the organism, these production mechanisms must be regulated by control mechanisms that select when a production is required and how it should be carried out. To operate on production mechanisms, control mechanisms need to procure information through measurement processes and evaluate possible actions. They are making decisions. In all organisms, these decisions are made by multiple different control mechanisms that are organized not hierarchically but heterarchically. In many cases, they employ internal models of features of the environment with which the organism must deal. Cognition, in the form of decision-making, is thus fundamental to living systems which must control their production mechanisms.

This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
Spontaneous electrical low-frequency oscillations: a possible role inHydraand all living systems
Authors: Hanson Alison
Published: January 2021

As one of the first model systems in biology, the basal metazoanHydrahas been revealing fundamental features of living systems since it was first discovered by Antonie van Leeuwenhoek in the early eighteenth century. While it has become well-established within cell and developmental biology, this tiny freshwater polyp is only now being re-introduced to modern neuroscience where it has already produced a curious finding: the presence of low-frequency spontaneous neural oscillations at the same frequency as those found in the default mode network in the human brain. Surprisingly, increasing evidence suggests such spontaneous electrical low-frequency oscillations (SELFOs) are found across the wide diversity of life on Earth, from bacteria to humans. This paper reviews the evidence for SELFOs in diverse phyla, beginning with the importance of their discovery inHydra, and hypothesizes a potential role as electrical organism organizers, which supports a growing literature on the role of bioelectricity as a ‘template’ for developmental memory in organism regeneration.

This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
Determination of quality characteristics by the reproduction of
grain vinegars reported in ancient literature
Authors: Kim Sun Hee , Kim Joo-Yeon , Gwon Hee-min , Kim So Young , Yeo Soo-Hwan
Published: January 2021

In this study, the quality characteristics of seven types of reproduced grain
vinegars were determined to promote the discovery and industrialization of
traditional vinegars reported in the ancient literature of the Joseon Dynasty.
The seven types of vinegars identified through literature review were prepared
using rice, glutinous rice, barley, autumn barley, millet, wheat, and
‘Makgeolli’ as the main raw materials, and
‘Mugukcho’, ‘Sajeolcho’, ‘Daemaekcho’,
‘Chunyeoncho’, ‘Sokmigukcho’,
‘Jinmaekcho’, and ‘Dongjucho’ were obtained by
employing various manufacturing methods. These vinegars had a pH of 3.3-3.6, but
the titration acidity was 0.99-4.3%, which was slightly lower than the
baseline standard for a vinegar. The vinegars contained nine types of organic
acids, 21 types of free amino acids, and their fragrance and taste determined
using an electronic nose and tongue varied with the fermentation time. In
particular, ‘Daemaekcho’ produced using barley had a lower pH and
higher acidity (4.3%), resulting in higher organic acid and amino acid
contents than those of other fermented vinegars. The sourness of
‘Daemaekcho’ and ‘Sajeolcho’ was identified by
determining the taste using an electronic tongue. This study is expected to
revive the vinegar industry by identifying and allowing the reproduction of the
representative grain vinegars of Korea based on the literature review of the
Joseon Dynasty.
Optimization of ‘Nuruk’, alcohol, and acetic acid
fermentations for producing vinegar from Acorus gramineus
roots
Authors: Gil Na-Young , Gwon Hee-Min , Yeo Soo-Hwan , Kim So-Young
Published: January 2021

In this study, we investigated the quality characteristics of medicinal vinegar
prepared from the roots of Acorus gramineus. We used barley
alcohol beverage along with both Rhizopus oryzae 82-7 and
Saccharomyces cerevisiae YM33 and vinegar culture with
Acetobacter pasteurianus A11-2 under the optimal conditions
for acetic acid fermentation. We manufactured the barley alcohol beverage with
11% alcohol content for fermentation with ‘Nuruk’ and
Saccharomyces cerevisiae YM33 at 25°C. When
fermented vinegar from Acorus gramineus roots for 10 days at
30°C with a starter, the pH and total acidity were 3.48 and 4.44%,
respectively, and the alcohol in vinegar was totally consumed. Besides, the
vinegar showed total polyphenol content of 870.13 mg TAE/mL at the
15th day, along with significant antioxidant activity. GC-MS
analysis revealed that the major volatiles in vinegar were methyl salicylate and
2-ethylhexanol, which have odors like those of mint and rose, respectively. In
contrast, the ethanol, 3-methyl-1-butanol, and 2-methyl-1-propanol contents,
which were high in the barley alcohol beverage, decreased in the vinegar that
was fermented by Acorus gramineus. Consequently, the vinegar
fermented by Acorus gramineus showed unique aromas and high
antioxidant activity.
Six-month Neurological and Psychiatric Outcomes in 236,379 Survivors of COVID-19
Authors: Taquet M. , Geddes J.R. , Husain M. , Luciano S. , Harrison P.J.
Published: January 2021

Background

Neurological and psychiatric sequelae of COVID-19 have been reported, but there are limited data on incidence rates and relative risks.

Methods

Using retrospective cohort studies and time-to-event analysis, we estimated the incidence of ICD-10 diagnoses in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; Parkinsonism; Guillain-Barré syndrome; nerve/nerve root/plexus disorders; myoneural/muscle disease; encephalitis; dementia; mood, anxiety, and psychotic disorders; substance misuse; and insomnia. Data were obtained from the TriNetX electronic health records network (over 81 million patients). We compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory infections using a Cox model. We investigated the effect on incidence estimates of COVID-19 severity, as proxied by hospitalization and encephalopathy (including delirium and related disorders).

Findings

236,379 patients survived a confirmed diagnosis of COVID-19. Among them, the estimated incidence of neurological or psychiatric sequelae at 6 months was 33.6%, with 12.8% receiving their first such diagnosis. Most diagnostic categories were commoner after COVID-19 than after influenza or other respiratory infections (hazard ratios from 1.21 to 5.28), including stroke, intracranial haemorrhage, dementia, and psychotic disorders. Findings were equivocal for Parkinsonism and Guillain-Barré syndrome. Amongst COVID-19 cases, incidences and hazard ratios for most disorders were higher in patients who had been hospitalized, and markedly so in those who had experienced encephalopathy. Results were robust to sensitivity analyses, including comparisons against an additional four index health events.

Interpretation

The study provides evidence for substantial neurological and psychiatric morbidity following COVID-19 infection. Risks were greatest in, but not limited to, those who had severe COVID-19. The information can help in service planning and identification of research priorities.

Funding

National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.