bluuebunny/crossref_metadata_2025_split huggingface dataset:
STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases
Authors: Pham Phuong Tran , Fukuda Daiju , Nishimoto Sachiko , Kim-Kaneyama Joo-Ri , Lei Xiao-Feng , Takahashi Yutaka , Sato Tomohito , Tanaka Kimie , Suto Kumiko , Kawabata Yutaka , Yamaguchi Koji , Yagi Shusuke , Kusunose Kenya , Yamada Hirotsugu , Soeki Takeshi , Wakatsuki Tetsuzo , Shimada Kenji , Kanematsu Yasuhisa , Takagi Yasushi , Shimabukuro Michio , Setou Mitsutoshi , Barber Glen N , Sata Masataka 
Published: April 2021

Abstract

Aims
Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis.

Methods and results
Apolipoprotein E-deficient (Apoe−/−) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe−/− mice. Genetic deletion of Sting in Apoe−/− mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe−/− mice. In contrast, bone marrow-specific STING expression in Apoe−/− mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP.

Conclusion
Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.
Non-canonical substrates for terpene synthases in bacteria are synthesized by a new family of methyltransferases
Authors: Piechulla Birgit , Zhang Chi , Eisenschmidt-Bönn Daniela , Chen Feng , Magnus Nancy 
Published: April 2021

ABSTRACT
The ‘biogenetic isoprene rule’, formulated in the mid 20th century, predicted that terpenoids are biosynthesized via polymerization of C5 isoprene units. The polymerizing enzymes have been identified to be isoprenyl diphosphate synthases, products of which are catalyzed by terpene synthases (TPSs) to achieve vast structural diversity of terpene skeletons. Irregular terpenes (e.g, C11, C12, C16 and C17) are also frequently observed, and they have presumed to be synthesized by the modification of terpene skeletons. This review highlights the exciting discovery of an additional route to the biosynthesis of irregular terpenes which involves the action of a newly discovered enzyme family of isoprenyl diphosphate methyltransferases (IDMTs). These enzymes methylate, and sometimes cyclize, the classical isoprenyl diphosphate substrates to produce modified, non-canonical substrates for specifically evolved TPSs. So far, this new pathway has been found only in bacteria. Structure and sequence comparisons of the IDMTs strongly indicate a conservation of their active pockets and overall topologies. Some bacterial IDMTs and TPSs appear in small gene clusters, which may facilitate future mining of bacterial genomes for identification of irregular terpene-producing enzymes. The IDMT-TPS route for terpenoid biosynthesis presents another example of nature's ingenuity in creating chemical diversity, particularly terpenoids, for organismal fitness.
Galerkin finite element approximation of a stochastic semilinear fractional subdiffusion with fractionally integrated additive noise
Authors: Kang Wenyan , Egwu Bernard A , Yan Yubin , Pani Amiya K 
Published: April 2021

AbstractA Galerkin finite element method is applied to approximate the solution of a semilinear stochastic space and time fractional subdiffusion problem with the Caputo fractional derivative of the order $ \alpha \in (0, 1)$, driven by fractionally integrated additive noise. After discussing the existence, uniqueness and regularity results, we approximate the noise with the piecewise constant function in time, in order to obtain a regularized stochastic fractional subdiffusion problem. The regularized problem is then approximated by using the finite element method in spatial direction. The mean squared errors are proved based on the sharp estimates of the various Mittag–Leffler functions involved in the integrals. Numerical experiments are conducted to show that the numerical results are consistent with the theoretical findings.
On the Weyl Problem in Minkowski Space
Authors: Smith Graham 
Published: April 2021

Abstract
Let $S$ be a closed surface of hyperbolic type. We show that, for every pair $(g_+,g_-)$ of negatively curved metrics over $S$, there exists a unique globally hyperbolic, maximal, and Cauchy compact Minkowski spacetime $X$ into which $(S,g_+)$ and $(S,g_-)$ isometrically embed as Cauchy surfaces in the future and past components, respectively.
Disease Progression in Children With Perinatal Human Immunodeficiency Virus Correlates With Increased PD-1+ CD8 T Cells That Coexpress Multiple Immune Checkpoints
Authors: Tailor Janki , Foldi Julia , Generoso Matthew , McCarty Bret , Alankar Aparna , Kilberg Max , Mwamzuka Mussa , Marshed Fatma , Ahmed Aabid , Liu Mengling , Borkowsky William , Unutmaz Derya , Khaitan Alka 
Published: April 2021

AbstractBackgroundPD-1 marks exhausted T cells, with weak effector functions. Adults living with human immunodeficiency virus (HIV) have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV.MethodsWe enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells; their coexpression with immune checkpoints (ICs) 2B4, CD160, and TIM3; correlates with immune activation and HIV disease progression; and HIV-specific and -nonspecific proliferative responses.ResultsPD-1+ CD8 T-cell frequencies are elevated in children with perinatal HIV and associated with disease progression. The majority of PD-1+ CD8 T cells coexpress additional ICs. ART initiation lowers total PD-1 levels and coexpression of multiple ICs. The frequency of PD-1+2B4+CD160+TIM3– in PD-1+ CD8 T cells predicts weaker HIV-specific proliferative responses, suggesting that this subset is functionally exhausted.ConclusionsChildren with perinatal HIV have high levels of PD-1+ CD8 T cells that are a heterogeneous population differentially coexpressing multiple ICs. Understanding the complex interplay of ICs is essential to guide the development of PD-1–directed immunotherapies for pediatric HIV remission and cure.
Severe Acute Respiratory Syndrome Coronavirus 2 Total and Subgenomic RNA Viral Load in Hospitalized Patients
Authors: Dimcheff Derek E , Valesano Andrew L , Rumfelt Kalee E , Fitzsimmons William J , Blair Christopher , Mirabelli Carmen , Petrie Joshua G , Martin Emily T , Bhambhani Chandan , Tewari Muneesh , Lauring Adam S 
Published: April 2021

Abstract

Background
Previous studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected for weeks after infection. The significance of this finding is unclear and, in most patients, does not represent active infection. Detection of subgenomic RNA has been proposed to represent productive infection and may be a useful marker for monitoring infectivity.

Methods
We used quantitative reverse-transcription polymerase chain reaction (RT-qPCR) to quantify total and subgenomic nucleocapsid (sgN) and envelope (sgE) transcripts in 185 SARS-CoV-2–positive nasopharyngeal swab samples collected on hospital admission and to relate to symptom duration.

Results
We find that all transcripts decline at the same rate; however, sgE becomes undetectable before other transcripts. The median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic compared to total RNA, suggesting that subgenomic transcript copy number is dependent on copy number of total transcripts. The mean difference between total and sgN is 16-fold and the mean difference between total and sgE is 137-fold. This relationship is constant over duration of symptoms, allowing prediction of subgenomic copy number from total copy number.

Conclusions
Subgenomic RNA may be no more useful in determining infectivity than a copy number threshold determined for total RNA.
The role of co-production in Learning Health Systems
Authors: Gremyr Andreas , Andersson Gäre Boel , Thor Johan , Elwyn Glyn , Batalden Paul , Andersson Ann-Christine 
Published: April 2021

Abstract

Background
Co-production of health is defined as ‘the interdependent work of users and professionals who are creating, designing, producing, delivering, assessing, and evaluating the relationships and actions that contribute to the health of individuals and populations’. It can assume many forms and include multiple stakeholders in pursuit of continuous improvement, as in Learning Health Systems (LHSs). There is increasing interest in how the LHS concept allows integration of different knowledge domains to support and achieve better health. Even if definitions of LHSs include engaging users and their family as active participants in aspects of enabling better health for individuals and populations, LHS descriptions emphasize technological solutions, such as the use of information systems. Fewer LHS texts address how interpersonal interactions contribute to the design and improvement of healthcare services.

Objective
We examined the literature on LHS to clarify the role and contributions of co-production in LHS conceptualizations and applications.

Method
First, we undertook a scoping review of LHS conceptualizations. Second, we compared those conceptualizations to the characteristics of LHSs first described by the US Institute of Medicine. Third, we examined the LHS conceptualizations to assess how they bring four types of value co-creation in public services into play: co-production, co-design, co-construction and co-innovation. These were used to describe core ideas, as principles, to guide development.

Result
Among 17 identified LHS conceptualizations, 3 qualified as most comprehensive regarding fidelity to LHS characteristics and their use in multiple settings: (i) the Cincinnati Collaborative LHS Model, (ii) the Dartmouth Coproduction LHS Model and (iii) the Michigan Learning Cycle Model. These conceptualizations exhibit all four types of value co-creation, provide examples of how LHSs can harness co-production and are used to identify principles that can enhance value co-creation: (i) use a shared aim, (ii) navigate towards improved outcomes, (iii) tailor feedback with and for users, (iv) distribute leadership, (v) facilitate interactions, (vi) co-design services and (vii) support self-organization.

Conclusions
The LHS conceptualizations have common features and harness co-production to generate value for individual patients as well as for health systems. They facilitate learning and improvement by integrating supportive technologies into the sociotechnical systems that make up healthcare. Further research on LHS applications in real-world complex settings is needed to unpack how LHSs are grown through coproduction and other types of value co-creation.
Activity of novel lactone ketolide nafithromycin against multicentric invasive and non-invasive pneumococcal isolates collected in India
Authors: Veeraraghavan Balaji , Varghese Rosemol , Saigal Karnika , Balasubramanian S , Bai P Sulochana Putli , Lal Y Binesh , Neeravi Ayyanraj , Baskar Pavithra , Anandhan Kavipriya , Kumar C P Girish , Jayaraman Yuvraj , Nag Vijaya Lakshmi , Baveja Sujata , J Bhavana , Joshi Shrikrishna A , Iyer Ranganathan 
Published: April 2021

Abstract

Background
India is among the nations reporting substantial healthcare burden linked to pneumococcal infections. Nafithromycin is a novel lactone ketolide antibiotic, which recently entered Phase 3 development in India for the indication of community-acquired bacterial pneumonia (CABP).

Objectives
To assess the in vitro activity of nafithromycin against serotyped invasive and non-invasive Streptococcus pneumoniae isolates, collected from nine medical centres across India.

Methods
A total of 534 isolates of S. pneumoniae were collected during 2015–20 and serotyped as per CDC protocol. A subset of erythromycin-non-susceptible S. pneumoniae (n = 200) was screened for the presence of erm(B) and mef(A/E) genes. A subset of MDR isolates (n = 54) were also subjected to MLST. The MICs of antibiotics were determined by the reference agar-dilution method (CLSI). Susceptibilities of the comparators were interpreted as per CLSI criteria.

Results
Fifty-nine distinct serotypes were identified among the 534 isolates. Among erythromycin-non-susceptible isolates, erm(B) and mef(A/E) genes were found in 49% and 59% strains respectively, while MLST showed clonal diversity. Azithromycin (67.6% non-susceptible) and clindamycin (31.8% non-susceptible) showed limited activity. Penicillin (for non-meningitis) or quinolone non-susceptibility was low (&lt;11% and &lt;6%, respectively). Nafithromycin showed potent activity with MIC50 and MIC90 of 0.015–0.03 and 0.06 mg/L, respectively, regardless of the macrolide resistance mechanisms.

Conclusions
Indian pneumococcal isolates show poor susceptibilities to macrolides, in concordance with the global trend. Nafithromycin overcomes erm as well as mef-mediated macrolide resistance mechanisms expressed individually or concurrently in S. pneumoniae. This study supports continued clinical development of nafithromycin for pneumococcal infections including CABP.
A novel interpretation of speciation, hybridization, and genetic population structure of the stone crabsMenippe mercenaria(Say, 1817–1818) andM. adinaWilliams & Felder, 1986 (Decapoda: Brachyura: Menippidae)
Authors: Seyoum Seifu , Gandy Ryan L , Crowley Claire E , Puchulutegui Cecilia 
Published: April 2021

AbstractMitochondrial DNA cytochrome oxidase (COI) and microsatellite DNA loci were used to better explain the speciation events, history of hybridization, and genetic population structure of the stone crabs Menippe adinaWilliams & Felder, 1986 and M. mercenaria (Say, 1817–1818). A survey of a 670-bp COI sequence of 711 stone crabs collected from Texas to North Carolina and from Belize, Central America showed the presence of two well-defined mtDNA lineages, Lin-A and Lin-B. Based on molecular clock calibrations of a published study these lineages shared a common ancestor between 1.5 to 1.8 million years. Lin-A was evident throughout the range of the two Menippe species, but Lin-B was found only in the eastern Gulf of Mexico and does not represent any of the two species. Our findings refute the claim that the eastern Gulf hybrid zone is the product of hybridization between M. adina and M. mercenaria. We propose that the hybrid zone is instead a relic of introgressive hybridization between the M. mercenaria of eastern Gulf stone crab nDNA Lin-AA that carries Lin-A and the new nDNA Lin-BB that carries Lin-B, forming the hybrid nDNA Lin-AB. Lin-B emerged from a founder effect in the Okefenokee Trough and introgressed into the eastern Gulf. There is no Lin-B in the Atlantic, hence no hybridization in that region. Using stone crab-specific microsatellite markers we found no evidence of an ongoing hybridization in the eastern Gulf and this region cannot be called a hybrid zone since hybridization here ceased probably soon after the last glacial episode. The microsatellite-marker analyses also suggested that the stone crab was geographically divided into four genetic clusters by three barriers to gene flow, the strongest of which is the one between the two species, M. adina and M. mercenaria, around Cape San Blas, Apalachicola Bay, Florida.
Social Ties and the Influence of Public Policies on Individual Opinions: The Case of Same-Sex Marriage Laws
Authors: Blasco Sylvie , Moreno Galbis Eva , Tanguy Jeremy 
Published: April 2021

AbstractThis paper evaluates if same-sex marriage (SSM) laws, approved in several European Union countries over the past decades, have contributed to favor gay-friendly opinions among people depending on their social interactions. We propose a dyadic model in which individuals learn about the social norm conveyed by a law through strong and weak ties. We show that the relative importance of these social ties in shaping individuals’ opinions depends on the alignment between the law and the local social norm. Using the 2002–2016 European Social Surveys, we test the theoretical predictions with a pseudo-panel dynamic difference-in-difference setting relying on the progressive adoption of SSM in European countries. We show that strong ties induce a lower increase in gay-friendly opinions following the adoption of SSM when the law is aligned with the local social norm. When the law clashes with this norm, strong ties induce a larger increase. (JEL J12, J18, K36, Z1).
Comparing Contributions of Passive and Active Tick Collection Methods to Determine Establishment of Ticks of Public Health Concern Within Illinois
Authors: Lyons Lee Ann , Brand Mary E , Gronemeyer Peg , Mateus-Pinilla Nohra , Ruiz Marilyn O’Hara , Stone Chris M , Tuten Holly C , Smith Rebecca L 
Published: April 2021

AbstractIn Illinois, between 1990 and 2017, tick-borne diseases in humans increased 10-fold, yet we have insufficient information on when and where people are exposed to vector ticks (Ixodida: Ixodidae). The aims of our research were to compare contributions of passive and active tick collection methods in determining establishment of ticks of public health concern and obtain information on tick distributions within Illinois. We used three surveillance strategies within the Illinois Tick Inventory Collaboration Network to gather information about the ticks of public health concern: 1) passive collection (voluntary submission by the public); 2) systematic collection (biweekly active surveillance); and 3) special collections (active collections in locations of special interest). Of collected adult and nymphal ticks, 436 were from passive collections, 142 from systematic collections, and 1,270 from special collections. Tick species distribution status changed in 36 counties. Our data provide noteworthy updates to distribution maps for use by public health agencies to develop prevention and control strategies. Additionally, the program built a network of collaborations and partnerships to support future tick surveillance efforts within Illinois and highlighted how the combination of the three surveillance strategies can be used to determine geographic spread of ticks, pinpoint locations in need of more surveillance, and help with long-term efforts that support phenology studies.
Case report: actinomycosis of the abdominal wall
Authors: Tarzi Mario , Douedari Alma , Aldakhil Rama , Danial Aghyad Kudra , Al-Haj Ahmad 
Published: April 2021

AbstractPrimary abdominal wall actinomycosis is rare, but even rarer when it comes to intestinal infiltration; it is usually misdiagnosed as a neoplasm in computed tomography till proved otherwise with pathological examination.We report a 59-year-old diabetic male presented with a year-old abdominal wall mass, diagnosed by pathology after surgical excisional biopsy, and treated with penicillin for 6 months. We recommend consideration of actinomycosis in cases of abdominal wall mass, especially in immunocompromised patients, as a differential diagnosis of neoplastic lesions.
Revealing the physical properties of gas accreting to haloes in the EAGLE simulations
Authors: Wright Ruby J , Lagos Claudia del P , Power Chris , Correa Camila A 
Published: April 2021

ABSTRACT
The inflow of cosmological gas on to haloes, while challenging to directly observe and quantify, plays a fundamental role in the baryon cycle of galaxies. Using the eagle suite of hydrodynamical simulations, we present a thorough exploration of the physical properties of gas accreting on to haloes – namely, its spatial characteristics, density, temperature, and metallicity. Classifying accretion as ‘hot’ or ‘ cold’ based on a temperature cut-off 105.5 K, we find that the covering fraction (fcov) of cold-mode accreting gas is significantly lower than the hot-mode, with z = 0 fcov values of ${\approx}50{{\ \rm per\ cent}}$ and ${\approx}80{{\ \rm per\ cent}}$, respectively. Active galactic nucleus (AGN) feedback in eagle reduces inflow fcov values by ${\approx}10{{\ \rm per\ cent}}$, with outflows decreasing the solid angle available for accretion flows. Classifying inflow by particle history, we find that gas on first-infall on to a halo is metal depleted by ≈2 dex compared to pre-processed gas, which we find to mimic the circum-galactic medium (CGM) in terms of metal content. We also show that high (low) halo-scale gas accretion rates are associated with metal-poor (rich) CGM in haloes below $10^{12}\, \mathrm{M}_{\odot }$, and that variation in halo-scale gas accretion rates may offer a physical explanation for the enhanced scatter in the star-forming main sequence at low (${\lesssim}10^{9}\, \mathrm{M}_{\odot }$) and high (${\gtrsim}10^{10}\, \mathrm{M}_{\odot }$) stellar masses. Our results highlight how gas inflow influences several halo- and galaxy-scale properties, and the need to combine kinematic and chemical data in order to confidently break the degeneracy between accreting and outgoing gas in CGM observations.
The impact of tidal friction evolution on the orbital decay of ultra-short-period planets
Authors: Alvarado-Montes Jaime A , Sucerquia Mario , García-Carmona Carolina , Zuluaga Jorge I , Spitler Lee , Schwab Christian 
Published: April 2021

ABSTRACT
Unveiling the fate of ultra-short-period (USP) planets may help us understand the qualitative agreement between tidal theory and the observed exoplanet distribution. Nevertheless, due to the time-varying interchange of spin–orbit angular momentum in star–planet systems, the expected amount of tidal friction is unknown and depends on the dissipative properties of stellar and planetary interiors. In this work, we couple structural changes in the star and the planet resulting from the energy released per tidal cycle and simulate the orbital evolution of USP planets and the spin-up produced on their host star. For the first time, we allow the strength of magnetic braking to vary within a model that includes photo-evaporation, drag caused by the stellar wind, stellar mass-loss, and stellar wind enhancement due to the in-falling USP planet. We apply our model to the two exoplanets with the shortest periods known to date, NGTS-10b and WASP-19b. We predict they will undergo orbital decay in time-scales that depend on the evolution of the tidal dissipation reservoir inside the star, as well as the contribution of the stellar convective envelope to the transfer of angular momentum. Contrary to previous work, which predicted mid-transit time shifts of ∼30–190 s over 10 yr, we found that such changes would be smaller than 10 s. We note this is sensitive to the assumptions about the dissipative properties of the system. Our results have important implications for the search for observational evidence of orbital decay in USP planets, using present and future observational campaigns.