bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying how restoration measures influence the presence of shorebirds: a case study on the use of artificial structures for restoring mussel reefs
Authors: Schotanus Jildou , Walles Brenda , Capelle Jacob J. , van de Koppel Johan , Bouma Tjeerd J.
Published: November 2023

Artificial structures are often used as a tool for habitat restoration and the recreation of degraded coastal ecosystems and their associated food webs. However, it is often unknown if and how these artificial structures may influence the habitat use of target species, thereby hampering restoration goals. In this study, we test how artificial barriers, deployed to enhance the creation of an intertidal mussel bed, influenced the mussel‐habitat use by two bird species under pressure, Eurasian oystercatchers and Eurasian curlews. Average bird presence was monitored using time‐lapse camera's from the start of the mussel bed restoration in August 2018 until April 2019. We found that in the first few months of the experiment, both oystercatchers and curlews avoided the restored mussel beds containing artificial structures in the form of metal barriers that act as traps for dislodged mussels. Thereafter, the presence of barriers had no negative influence on the average presence of oystercatchers or curlews. In fact, curlews were significantly attracted to the mussel beds with barriers in January and February. In addition, we found a negative effect of the presence of European herring gulls on the presence of oystercatchers and curlews. The higher herring gull densities in the first 2 months of the experiment might explain the lower‐than‐expected curlew and oystercatcher densities observed in August. To our knowledge, no other studies have investigated the effect of artificial restoration structures on the abundance or habitat use of specific shorebirds.
A COVID‐19 cluster analysis in an office: Assessing the long‐range aerosol and fomite transmissions with infection control measures
Authors: Mizukoshi Atsushi , Okumura Jiro , Azuma Kenichi
Published: November 2023

Simulated exposure to severe acute respiratory syndrome coronavirus 2 in the environment was demonstrated based on the actual coronavirus disease 2019 cluster occurrence in an office, with a projected risk considering the likely transmission pathways via aerosols and fomites. A total of 35/85 occupants were infected, with the attack rate in the first stage as 0.30. It was inferred that the aerosol transmission at long‐range produced the cluster at virus concentration in the saliva of the infected cases on the basis of the simulation, more than 108 PFU mL−1. Additionally, all wearing masks effectiveness was estimated to be 61%–81% and 88%–95% reduction in risk for long‐range aerosol transmission in the normal and fit state of the masks, respectively, and a 99.8% or above decline in risk of fomite transmission. The ventilation effectiveness for long‐range aerosol transmission was also calculated to be 12%–29% and 36%–66% reductions with increases from one air change per hour (ACH) to two ACH and six ACH, respectively. Furthermore, the virus concentration reduction in the saliva to 1/3 corresponded to the risk reduction for long‐range aerosol transmission by 60%–64% and 40%–51% with and without masks, respectively.
A Decomposition of Economic Vulnerability Among Indigenous and Non‐Indigenous Adults in Canada
Authors: Watson Barry , Daley Angela
Published: November 2023

Using the 2004–2007 and 2008–2011 panels of the Canadian Survey of Labour and Income Dynamics, we examine earnings and employment disparities between Indigenous and non‐Indigenous adults. While an income gap exists and tends not to significantly change over time, taxes and transfers reduce it by almost 40 percent. Further, the gap is generally largest at the bottom of the income distribution. The explained component of the gap is primarily due to differences in education, particularly for young workers, and although the unexplained portion decreases over time, this is due to increased differences in observed labor market characteristics, implying that labor market discrimination may be on the rise. In addition, the probability of joblessness is higher for Indigenous adults and the male gap has increased. Results are robust to a bounding technique that adjusts for labor force participation differences and tend to be driven by First Nations (as opposed to Métis) adults.
Why inconsistent intentional states underlie our grasp of objects
Authors: Golan Rea
Published: November 2023

Several authors maintain that we are capable of having inconsistent intentional states, either in cases of illusion, in certain cases of imagination, or because the observable world is (partly) inconsistent and we perceive it as such. These views are all premised on the assumption that inconsistent intentional states—even if acknowledged—are peculiar and have nothing essential to do with our perceptual capacities. In the present article, I would like to present, and argue for, a much stronger thesis: that inconsistent intentional states underlie the possibility of having intentional content in mind. I argue for this thesis based on a Husserlian phenomenological analysis of our grasp of objects, which I formulate in terms of incompatibility semantics.
A multidimensional examination of children's endorsement of gender stereotypes
Authors: Miller Cindy Faith , Wheeler Lorey A. , Woods Bobbi
Published: November 2023

The present research applied a multidimensional framework to the study of gender stereotypes by investigating whether elementary school children display different levels of endorsement when considering distinct gender stereotype constructs (ability, category, and interest) and feminine versus masculine stereotypes. Study 1 (N = 403) compared children's ability and category beliefs using a set of gender‐neutral skill items. Study 2 (N = 539) extended this research by examining whether children showed different patterns of ability and category decisions for feminine versus masculine occupational items. Study 3 (N = 974) furthered our understanding of the construct dimension by comparing children's interest and ability decisions within the STEM domain. Findings revealed that older elementary school children endorsed ability stereotypes more strongly than category stereotypes and, across all age groups, children endorsed interest stereotypes more strongly than ability stereotypes. Findings also revealed age differences in how children think about masculine versus feminine stereotypes. For masculine stereotypes, younger children showed stronger endorsement than older children; however, for feminine stereotypes, the reverse pattern was found such that older children showed more stereotyped thinking than younger children. The present study illustrates the benefits of employing a multidimensional framework to gain a more nuanced understanding of how children apply their increasing knowledge of gender stereotypes.
Caring peripheries: How care practitioners respond to processes of peripheralisation
Authors: van Pijkeren Nienke , Wallenburg Iris , van de Bovenkamp Hester , Wiig Siri , Bal Roland
Published: November 2023

The centralisation of acute health care is a key policy concern in many countries. Less attention has been given to the side effects of centralisation: peripheralisation, occurring mainly in rural areas and post‐industrial towns. In this research, we start filling this gap by exploring how this trend of concentration of health care can contribute to a phenomenon referred to as ‘discursive peripheralisation’. This article contributes to the literature on discursive peripheralisation by focusing on how actors, in our case acute care practitioners, cope with or oppose such processes. We draw on empirical data from two healthcare regions in different geographical contexts in Norway and The Netherlands. In these regions, we zoom in on the work of care practitioners and how they, in relation to care organisations and local authorities, aim to organise care for patients in ‘the periphery’ and how this contributes to more diverse and alternative narratives and practices of health care in these areas. Our findings offer important insights for both rural and regional policy. We conclude that other narratives, for instance, about perceptions of quality of care should be considered to avoid too much emphasis on the disadvantages faced by peripheral areas, compared to their urban counterparts.
Asymptotic approximations of expectations of power means
Authors: Burić Tomislav , Mihoković Lenka
Published: November 2023

In this paper we study how the expectations of power means behave asymptotically as some relevant parameter approaches infinity and how to approximate them accurately for general nonnegative continuous probability distributions. We derive approximation formulae for such expectations as distribution mean increases, and apply them to some commonly used distributions in statistics and financial mathematics. By numerical computations we demonstrate the accuracy of the proposed formulae which behave well even for smaller sample sizes. Furthermore, analysis of behavior depending on sample size contributes to interesting connections with the power mean of probability distribution.
A global LC–MS2‐based methodology to identify and quantify anionic phospholipids in plant samples
Authors: Genva Manon , Fougère Louise , Bahammou Delphine , Mongrand Sébastien , Boutté Yohann , Fouillen Laetitia
Published: November 2023

Anionic phospholipids (PS, PA, PI, PIPs) are low‐abundant phospholipids with impactful functions in cell signaling, membrane trafficking and cell differentiation processes. They can be quickly metabolized and can transiently accumulate at defined spots within the cell or an organ to respond to physiological or environmental stimuli. As even a small change in their composition profile will produce a significant effect on biological processes, it is crucial to develop a sensitive and optimized analytical method to accurately detect and quantify them. While thin‐layer chromatography (TLC) separation coupled with gas chromatography (GC) detection methods already exist, they do not allow for precise, sensitive, and accurate quantification of all anionic phospholipid species. Here we developed a method based on high‐performance liquid chromatography (HPLC) combined with two‐dimensional mass spectrometry (MS2) by MRM mode to detect and quantify all molecular species and classes of anionic phospholipids in one shot. This method is based on a derivatization step by methylation that greatly enhances the ionization, the separation of each peak, the peak resolution as well as the limit of detection and quantification for each individual molecular species, and more particularly for PA and PS. Our method universally works in various plant samples. Remarkably, we identified that PS is enriched with very long chain fatty acids in the roots but not in aerial organs of Arabidopsis thaliana. Our work thus paves the way for new studies on how the composition of anionic lipids is finely tuned during plant development and environmental responses.
Triacylglycerol lipase, OsSG34, plays an important role in grain shape and appearance quality in rice
Authors: Jin Xiaoli , Chen Jian , Khan Asadullah , Chen Ziyan , Gao Rui , Lu Yingying , Zheng Xi
Published: November 2023

Optimal grain‐appearance quality is largely determined by grain size. To date, dozens of grain size‐related genes have been identified. However, the regulatory mechanism of slender grain formation is not fully clear. We identified the OsSG34 gene by map‐based cloning. A 9‐bp deletion on 5’‐untranslated region of OsSG34, which resulted in the expression difference between the wild‐type and sg34 mutant, led to the slender grains and good transparency in sg34 mutant. OsSG34 as an α/β fold triacylglycerol lipase affected the triglyceride content directly, and the components of cell wall indirectly, especially the lignin between the inner and outer lemmas in rice grains, which could affect the change in grain size by altering cell proliferation and expansion, while the change in starch content and starch granule arrangement in endosperm could affect the grain‐appearance quality. Moreover, the OsERF71 was identified to directly bind to cis‐element on the mutant site, thereby regulating the OsSG34 expression. Knockout of three OsSG34 homologous genes resulted in slender grains as well. The study demonstrated OsSG34, involved in lipid metabolism, affected grain size and quality. Our findings suggest that the OsSG34 gene could be used in rice breeding for high yield and good grain‐appearance quality via marker‐assisted selection and gene‐editing approaches.
Impact of palliative‐intent radiotherapy with or without chemotherapy on lameness in flat coat retrievers with localised periarticular histiocytic sarcoma – a retrospective cohort, single institution study
Authors: Odatzoglou Petros , Kearns Thomas , Pittaway Charlie , Dobson Jane M.
Published: November 2023

Histiocytic sarcoma (HS) is a common tumour in flat coat retrievers (FCRs) often affecting periarticular tissues and joints. Palliative‐intent radiotherapy, seeks to achieve local tumour control, pain relief and improve limb function. However, the effect of palliative‐intent radiotherapy on analgesic levels of dogs with localised HS has not been studied. We hypothesised that palliative‐intent radiotherapy could improve lameness in dogs affected by localised HS. This study aimed to assess the impact of palliative‐intent radiotherapy on lameness of FCRs with localised HS. A retrospective cohort single institution study was performed. Medical records of FCR dogs with HS that received external beam radiotherapy between 2003 and 2022 were reviewed and included demographic, staging, severity of baseline lameness, therapeutic management and outcome data. Descriptive statistics, McNemar's chi‐squared test, Fisher's exact test and Kaplan–Meier analysis were used for statistical analysis. Thirty‐nine dogs were included with a median age of 7.2 years, 25 were male and 14 were female. HS was most commonly located in the forelimb (29 dogs, 74.3%), affecting the shoulder joint (19 dogs, 48.7%). Staging was performed in all 39 dogs with 22 (56.4%) dogs having localised HS, six (15.3%) dogs had localised HS with node metastasis and 11 (28.2%) dogs had localised HS with systemic metastasis. All dogs received palliative‐intent hypo‐fractionated radiation therapy, 32 (82%) dogs showed improvement in lameness. In conclusion, palliative intent radiation treatment has an analgesic effect reducing lameness or clinical signs associated with affected tumour‐bearing joints.
Fast Optimal Design of Shell-Graded-Infill Structures With Explicit Boundary by a Hybrid MMC-AABH Plus Approach
Authors: Bi Yikang , Li Shaoshuai , Zhu Yichao
Published: November 2023

In this study, a hybrid MMC-AABH plus approach is developed for the fast optimal design of shell-graded-infill structures. The key idea is to use a proper description about the graded microstructural infill and the coating shell. To this end, a set of moving morphable components is adopted to represent the boundary of the coating shell, while the graded-infill is embodied by spatially varying orthotropic porous configurations. Under such a treatment, with a small number of design variables, both the boundary of the coating shell and the graded microstructure infill can be optimized simultaneously. Other attractive features of the present study are summarized as follows. First, the smooth variation across the microstructural infill can be automatically satisfied based on the proposed approach compared with other similar methods. Second, with the use of the extreme value principle of Laplace equation, the minimum feature size can be explicitly controlled during the optimization. Finally, compared with other methods in the frontier, the approach proposed in the present study enjoys a considerable reduction in the computation cost and can obtain a near-optimal design of the coating structures. The effectiveness of the proposed approach is further demonstrated with numerical examples.
Evidence of Atlantic midshipman (Porichthys plectrodon) vocalizations from an unmanned surface vehicle in the U.S. South Atlantic
Authors: Iafrate Joseph , Reyier Eric , Ahr Bonnie , Carroll Alexandra , Rice Aaron N. , Dossot Georges , Watwood Stephanie L. , Murie Debra
Published: November 2023

An unmanned surface vehicle (USV; Wave Glider) was deployed to study the coastal soundscape in shallow (less than 30 m) coastal waters off the coast of Cape Canaveral, FL, in July 2020 and January 2022. These surveys documented temporal and seasonal trends in biological sounds across a variety of habitats within an 812-km2 survey area, including sand shoals, sand-mud plains, and natural hardbottom. Among a broader diversity of identifiable and unidentifiable fish choruses recorded during the survey, a distinct and previously unidentified fish chorus was recorded; corroborating evidence suggests it and other sounds with similar spectral properties may be produced by Atlantic midshipman. Putative Atlantic midshipman sounds included an agnostic grunt and a seasonal chorus of persistent hums that peaked 3 h after sunset in the summer survey. While Atlantic midshipman have been demonstrated to have well-developed sonic muscles on their swim bladder, their acoustic behavior has not been previously described. Our use of a mobile passive acoustic platform combined with bottom sampling of fish communities highlights an important opportunity to identify previously undocumented biological sound sources in coastal habitats.
Brittney Griner, Intersectionality, and “Woke Politics”: A Critical Examination of Brittney Griner’s Return to the United States
Authors: Keaton Ajhanai C.I. , Frederick Evan , Branch Keisha , Pegoraro Ann
Published: November 2023

In February of 2022, professional women’s basketball player Brittney Griner was detained in Russia on drug possession charges. Her detainment was a trending Twitter topic demonstrating the cultural, political, and social state of the United States, specifically pertaining to race, gender, nationality, and LGBTQ matters. The purpose of this study was to analyze what Brittney Griner’s release from Russia tells us about social power relations and contemporary social political matters on the axis of race, gender, and sexual orientation. We organized the data to determine three distinct, yet interconnected themes: (a) Woke Politics at the Intersection of Race, Gender, and Queerness; (b) Preferential Treatment at the Expense of Whiteness Informed Patriotism; and (c) Intersectionality as Political Pandering.
Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8
+
T cells in patients with advanced NSCLC
Authors: Naigeon Marie , Roulleaux Dugage Matthieu , Danlos François-Xavier , Boselli Lisa , Jouniaux Jean-Mehdi , de Oliveira Caroline , Ferrara Roberto , Duchemann Boris , Berthot Caroline , Girard Lou , Flippot Ronan , Albiges Laurence , Farhane Siham , Saulnier Patrick , Lacroix Ludovic , Griscelli Frank , Roman Gabriel , Hulett Tyler , Marabelle Aurélien , Cassard Lydie , Besse Benjamin , Chaput Nathalie
Published: November 2023

Circulating senescent CD8
+
T (T
8
sen) cells are characterized by a lack of proliferative capacities but retain cytotoxic activity and have been associated to resistance to immunotherapy in patients with advanced non–small cell lung cancer (aNSCLC). We aimed to better characterize T
8
sen and to determine which factors were associated with their accumulation in patients with aNSCLC. Circulating T
8
sen cells were characterized by a higher expression of SA-βgal and the transcription factor T-bet, confirming their senescent status. Using whole virome profiling, cytomegalovirus (CMV) was the only virus associated with T
8
sen. CMV was necessary but not sufficient to explain high accumulation of T
8
sen (T
8
sen
high
status). In CMV
+
patients, the proportion of T
8
sen cells increased with cancer progression. Last, CMV-induced T
8
sen
high
phenotype but not CMV seropositivity itself was associated with worse progression-free and overall survival in patients treated with anti–PD-(L)1 therapy but not with chemotherapy. Overall, CMV is the unique viral driver of T
8
sen-driven resistance to anti–PD-(L)1 antibodies in patients with aNSCLC.
Observational evidence of strong forcing from aerosol effect on low cloud coverage
Authors: Yuan Tianle , Song Hua , Wood Robert , Oreopoulos Lazaros , Platnick Steven , Wang Chenxi , Yu Hongbin , Meyer Kerry , Wilcox Eric
Published: November 2023

Aerosols cool Earth’s climate indirectly by increasing low cloud brightness and their coverage (Cf), constituting the aerosol indirect forcing (AIF). The forcing partially offsets the greenhouse warming and positively correlates with the climate sensitivity. However, it remains highly uncertain. Here, we show direct observational evidence for strong forcing from Cf adjustment to increased aerosols and weak forcing from cloud liquid water path adjustment. We estimate that the Cf adjustment drives between 52% and 300% of additional forcing to the Twomey effect over the ocean and a total AIF of −1.1 ± 0.8 W m
−2
. The Cf adjustment follows a power law as a function of background cloud droplet number concentration,

N
d

. It thus depends on time and location and is stronger when

N
d

is low. Cf only increases substantially when background clouds start to drizzle, suggesting a role for aerosol-precipitation interactions. Our findings highlight the Cf adjustment as the key process for reducing the uncertainty of AIF and thus future climate projections.
Tropical mountain ice core δ
18
O: A Goldilocks indicator for global temperature change
Authors: Liu Zhengyu , Bao Yuntao , Thompson Lonnie G. , Mosley-Thompson Ellen , Tabor Clay , Zhang Guang J. , Yan Mi , Lofverstrom Marcus , Montanez Isabel , Oster Jessica
Published: November 2023

Very high tropical alpine ice cores provide a distinct paleoclimate record for climate changes in the middle and upper troposphere. However, the climatic interpretation of a key proxy, the stable water oxygen isotopic ratio in ice cores (δ
18
O
ice
), remains an outstanding problem. Here, combining proxy records with climate models, modern satellite measurements, and radiative-convective equilibrium theory, we show that the tropical δ
18
O
ice
is an indicator of the temperature of the middle and upper troposphere, with a glacial cooling of −7.35° ± 1.1°C (66% CI). Moreover, it severs as a “Goldilocks-type” indicator of global mean surface temperature change, providing the first estimate of glacial stage cooling that is independent of marine proxies as −5.9° ± 1.2°C. Combined with all estimations available gives the maximum likelihood estimate of glacial cooling as −5.85° ± 0.51°C.
Immunological drivers of amyotrophic lateral sclerosis
Authors: Gendron Tania F. , Petrucelli Leonard
Published: November 2023

Amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease involving complex genetic and environmental factors, is associated with neuroinflammation. Preclinical and clinical studies support immune system involvement in ALS pathogenesis, thereby spurring investigations into potential pathogenic mechanisms, immune response biomarkers, and ALS therapeutics.
Current status of amyloid-targeting immunotherapies for Alzheimer’s disease
Authors: Tabor G. Travis , Holtzman David M.
Published: November 2023

Anti-amyloid antibodies are moving from clinical trials into patients to treat early clinical stages of Alzheimer’s disease.
mRNAs encoding self-DNA reactive cGAS enhance the immunogenicity of lipid nanoparticle vaccines
Authors: Zhivaki Dania , Gosselin Emily A. , Sengupta Debrup , Concepcion Holly , Arinze Chisom , Chow Jonathan , Nikiforov Anastasia , Komoroski Veronica , MacFarlane Carolyn , Sullivan Caitlin , Kagan Jonathan C.
Published: November 2023

Lipid nanoparticle (LNP)-encapsulated mRNAs have emerged as effective vaccination tools to stimulate immunity. The most common application of this technology is to deliver mRNAs that encode antigenic proteins to dendritic cells (DCs), which then stimulate antigen-specific lymphocyte responses. It is unclear whether other immunostimulatory DC activities necessary for vaccine efficacy, beyond antigen presentation, can be induced via mRNA-encoded proteins. Herein, we report an mRNA encoding a self-DNA reactive variant of the enzyme cyclic GMP-AMP synthase (cGAS), known as cGAS∆N. cGAS∆N produces the cyclic dinucleotide cGAMP upon binding intra-mitochondrial DNA. cGAMP binds the protein STING, which activates innate immune responses that stimulate T cells. We found that when delivered to DCs via LNPs, mRNA-encoded cGAS∆N induced the upregulation of chemokine receptors, T cell costimulatory molecules, major histocompatibility complex proteins, pro-inflammatory cytokines and type I interferons from murine and human DCs. These activities exceeded the immunostimulatory activities of mRNA-encoded antigens delivered via LNPs. Co-immunization of mice with antigen-LNPs and cGAS∆N-LNPs led to the robust production of antigen-specific IFNγ-producing T cells. These T cell responses were durable and circulated through the lymphatics, blood, and lungs. Immunizations with antigen-LNPs alone, akin to what are used in the clinic, stimulated weak and transient T cell responses. Antibody responses to antigen-LNPs were biased towards type I isotypes when co-injected with cGAS∆N-LNPs, as compared to immunizations with antigen-LNPs alone. These findings establish the enzyme cGAS∆N as a catalytic adjuvant, which may prove useful in enhancing the immunogenicity of nucleic acid-based vaccines.

IMPORTANCE

Nucleic acid-based vaccines hold promise in preventing infections and treating cancer. The most common use of this technology is to encode antigenic proteins on mRNAs that are delivered to cells via lipid nanoparticle (LNP) formulations. In this study, we discovered that immunostimulatory proteins can also be encoded on mRNAs in LNPs. We found that an active mutant of the enzyme cGAS, referred to as cGAS∆N, acts as a catalytic adjuvant in LNP-encapsulated mRNA vaccines. The delivery of cGAS∆N mRNA via LNPs in combination with antigen mRNA-LNPs led to durable antigen-specific IFNγ-producing T cells that exceeded the efficiency of antigen-LNPs similar to those currently used in the clinic. This strategy did not compromise B cell responses; rather it induced Th1-biased antibody isotypes. This work unveils new vaccine design strategies using mRNA-encoded catalytic adjuvants that could be ideal for generating CD8
+
T cell and B cell responses for immunotherapies.
Draft genome sequence of
Cupriavidus
sp. strain TKC, isolated from a γ-hexachlorocyclohexane-degrading community
Authors: Kato Hiromi , Ohtsubo Yoshiyuki , Hirano Shoko , Masuda Sachiko , Shibata Arisa , Shirasu Ken , Nagata Yuji
Published: November 2023

Cupriavidus
sp. strain TKC was isolated from a microbial community enriched with γ-hexachlorocyclohexane (γ-HCH). This strain did not show γ-HCH-degrading activity but was one of the major members of the community. Here, we present the draft genome sequence of the strain TKC with a size of 7 Mb.
Draft genome sequence of perfluorinated acids C
7
–C
9
degrading bacterium
Pseudomonas mosselii
5(3), isolated from soil contaminated with pesticides
Authors: Chetverikov Sergey , Hkudaigulov Gaisar , Sharipov Danil , Starikov Sergey , Delegan Yanina
Published: November 2023

The P
seudomonas mosselii
5(3) strain is a potential degrader of persistent perfluorinated pollutants, particularly C
7
–C
9
perfluorinated acids. The genome of the strain has been fully sequenced. It consists of a chromosome with a length of 5,676,241 base pairs and a G-C content of 64.38%.
Development and validation of a multiplex real-time PCR assay for detection and quantification of
Streptococcus pneumoniae
in pediatric respiratory samples
Authors: Butler Molly , Breazeale Garrett , Mwangi Eric , Dowell Elaine , Dominguez Samuel R. , Lamberth Linda , Hultén Kristina G. , Jung Sarah A.
Published: November 2023

Streptococcus pneumoniae
(
Spn
) is a bacterial pathogen that causes a range of disease manifestations in children, from acute otitis media to pneumonia, septicemia, and meningitis. Primary
Spn
laboratory diagnostic identification methods include culture, antigen testing, single-plex real-time PCR, and syndromic PCR panels. However, each method lacks sensitivity, specificity, and/or cost efficiency. We developed and validated a quantitative, multiplex PCR assay using three
Spn
genomic targets (
lytA, piaB
, and SP2020) for improved sensitivity and specificity to detect
Spn
in pleural fluid (PF), bronchoalveolar lavage (BAL), tracheal aspirate (TA), and upper respiratory (UR, research only) samples. Validation testing included analytical sensitivity (limit of detection), specimen storage, analytical specificity (cross-reactivity), and accuracy studies. Limit of detection is 500 genome copies/mL in lower respiratory samples and 100 copies/mL in upper respiratory specimens, with a quantification range of 1,000 to 10,000,000 copies/mL. Specimens can be stored frozen at least 60 days and
Spn
DNA is stable through three freeze-thaw cycles. No cross-reactivity was observed against 20 closely related microorganisms and/or microorganisms that can be detected in similar sample types, including
Streptococcus pseudopneumoniae
. In testing of residual clinical specimens,
Spn
was detected in 5 of 23 (21.7%) PF, 2 of 19 (10.5%) BAL, 1 of 20 (5.0%) TA, and 44 of 178 (24.7%) UR residual specimens. For accuracy studies, 98 specimens were tested and overall percent agreement with a qualitative,
lytA
-based comparator assay was 96.9% across all sample types. This multiplex, quantitative PCR assay is a sensitive and specific method for
Spn
detection in pediatric respiratory samples.

IMPORTANCE

Streptococcus pneumoniae
(
Spn
) is the world’s leading cause of lower respiratory tract infection morbidity and mortality in children. However, current clinical microbiological methods have disadvantages.
Spn
can be difficult to grow in laboratory conditions if a patient is pre-treated, and
Spn
antigen testing has unclear clinical utility in children. Syndromic panel testing is less cost-effective than targeted PCR if clinical suspicion is high for a single pathogen. Also, such testing entails a full, expensive validation for each panel target if used for multiple respiratory sources. Therefore, better diagnostic modalities are needed. Our study validates a multiplex PCR assay with three genomic targets for semi-quantitative and quantitative
Spn
molecular detection from lower respiratory sources for clinical testing and from upper respiratory sources for research investigation.
Diversity for endoribonuclease nsp15-mediated regulation of alpha-coronavirus propagation and virulence
Authors: Xie Yunfei , Chen Chener , Zhang Ding , Jiao Zhe , Chen Yixi , Wang Gang , Tan Yubei , Zhang Wanpo , Xiao Shaobo , Peng Guiqing , Shi Yuejun
Published: November 2023

Endoribonuclease non-structural protein 15 (nsp15) (EndoU) is conserved among coronaviruses (CoVs) and is crucial for viral replication, evasion of the innate immune system, and virulence. EndoU-deficient CoVs can activate the interferon (IFN) response and attenuate their virulence, and nsp15 is considered the target of attenuated vaccine development. Among alpha-CoVs, transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) cause lethal diseases in piglets and cats, but the role of EndoU in viral propagation and virulence remains unclear. Here, we verified the TGEV and FIPV EndoU active sites His226 and His241 and found that the antagonization of SeV-induced IFN-β production by nsp15 depends on its EndoU activity. Furthermore, we constructed infectious clones of wild-type (WT) and EndoU-deficient (EnUmt) TGEV and FIPV. Unexpectedly, we found that both the WT and EnUmt viruses propagated efficiently in multiple types of immunocompetent (PK-15, IPI-2I, ST, CRFK, F81, and Fcwf-4) cells. Moreover, the results of infection experiments showed that compared with piglets and cats infected with the WT, the EnUmt virus-infected piglets and cats did not exhibit significantly reduced mortality, tissue injury, or viral shedding. Specially, the death of cats infected with EnUmt-FIPV occurred earlier than that of cats infected with WT. Hence, our results suggest that the function of EndoU is conserved, but nsp15-mediated regulation of the propagation and pathogenesis of CoVs are diverse. Our findings provide a reference for an in-depth understanding of EndoU-mediated immune escape and pathogenicity in CoVs.

IMPORTANCE

Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target discovery. Whether the EndoU activity of CoV nsp15, as a virulence-related protein, has a diverse effect on viral virulence needs to be further explored. Here, we found that the transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) nsp15 proteins antagonize SeV-induced interferon-β (IFN-β) production in human embryonic kidney 293 cells. Interestingly, compared with wild-type infection, infection with EnUmt-TGEV or EnUmt-FIPV did not change the IFN-β response or reduce viral propagation in immunocompetent cells. The results of animal experiments showed that EnUmt viruses did not reduce the clinical presentation and mortality caused by TGEV and FIPV. Our findings enrich the understanding of nsp15-mediated regulation of alpha-CoV propagation and virulence and reveal that the conserved functions of nonstructural proteins have diverse effects on the pathogenicity of CoVs.
Intra–Neo-Tethyan subduction initiation inferred from the Indawgyi mafic rocks in the Central Ophiolite Belt, Myanmar
Authors: Zhang Qinghua , Chen Yi , Chen Si , Su Bin , Li Yibing , Shi Kaihui , Aung Me M. , Sein Kyaing
Published: November 2023

Geological evidence has demonstrated the presence of an intra–Neo-Tethyan subduction system during the Cretaceous. However, when and how this intra-oceanic subduction was initiated, especially for the eastern Neo-Tethys, are still not well constrained. Here we present geochemical and geochronological analyses of the Indawgyi mafic rocks from the Central Ophiolite Belt in the West Burma Block (Myanmar), which record early forearc spreading during the intra–Neo-Tethyan subduction initiation. Zircon U-Pb ages of gabbros indicate the ophiolitic crust formation at ca. 120 Ma. Gabbros show mid-oceanic-ridge basalt–like rare earth element patterns and depleted Sr-Nd-Pb isotopic compositions with negative anomalies of high field strength elements (e.g., Nb, Ta, Zr, and Hf), similar to forearc basalt characteristics. Basalts show more slab-derived component signatures than the gabbros and represent mantle wedge magmas most likely formed between forearc spreading and arc maturation. These data, together with regional geological records and geophysical observations, suggest that the Indawgyi gabbros were derived from an intra–Neo-Tethyan forearc setting during the early stage of subduction initiation. Considering the timing of supra-subduction zone ophiolites and metamorphic sole in the Indo-Burma Range, we propose that spontaneous subduction initiation and sinking of the eastern Neo-Tethyan lithosphere during the Early Cretaceous (ca. 120 Ma) led to formation of the Indawgyi forearc crust, whereas subsequent mature subduction resulted in the Middle Cretaceous (ca. 108–90 Ma) arc magmatism in the West Burma Block. These findings confirm the double-subduction model of the Neo-Tethys Ocean and shed new light on the intra–Neo-Tethyan subduction initiation.
Long-term outcomes of an educational paediatric antimicrobial stewardship programme: a quality improvement study
Authors: Aboza Garcia Marta , Goycochea-Valdivia Walter , Peñalva Germán , Falcon Neyra Lola , Moleón Ruiz Marta , Rodriguez-Villodres Angel , Montero Valladares Cristina , Olbrich Peter , Sánchez-Valderrabanos Elia , Jiménez Francisco , Molina Maria , Moreno Madueño Gloria , Valencia Martin Raquel , Gil Navarro Maria Victoria , Molina Jose , Neth Olaf , Cisneros Jose Miguel
Published: November 2023

Background and objectives

Antimicrobial stewardship programmes (ASPs) have resulted in antimicrobial consumption (AMC) reduction and quality of prescription (QOP) improvement. However, evidence of ASP impact in paediatrics is still limited. This study aims to assess a paediatric ASP long-term outcomes.

Methods

A quality improvement study assessed by a interrupted time series analysis was conducted in a paediatric tertiary hospital. QOP expressed as proportion of adequate prescriptions, AMC measured by defined daily dose incidence per 1000 occupied bed days, incidence density of bloodstream infections (BSIs) and its related all-cause crude death rate (CDR) were compared between pre (from January 2013 to December 2015) and post (from January 2016 to December 2019) ASP activities intensification, which included a dedicated paediatric infectious diseases physician to actively perform educational interviews with prescribers.

Results

Inappropriate prescribing showed a significant downward shift associated to the intervention with a −51.4% (−61.2% to −41.8%) reduction with respect to the expected values. Overall AMC showed no trend change after the intervention. For neonatology a

28.8% (−36.8% to −20.9%) reduction was observed. Overall anti-pseudomonal cephalosporin use showed a −51.2% (−57.0% to −45.4%) reduction. Decreasing trends were observed for carbapenem use, with a quarterly per cent change (QPC) of −2.4% (−4.3% to −0.4%) and BSI-related CDR (QPC=−3.6%; −5.4% to −1.7%) through the study period. Healthcare-associated multi-drug-resistant BSI remained stable (QPC=2.1; −0.6 to 4.9).

Conclusions

Intensification of counselling educational activities within an ASP suggests to improve QOP and to partially reduce AMC in paediatric patients. The decreasing trends in mortality remained unchanged.
Infant fat mass and later child and adolescent health outcomes: a systematic review
Authors: Amati Federica , McCann Lucy , Castañeda-Gutiérrez Eurídice , Prior Emily , van Loo-Bouwman Carolien Annika , Abrahamse-Berkeveld Marieke , Oliveros Elena , Ozanne Susan , Symonds Michael Edward , Chang Ching-Yu , Modi Neena
Published: November 2023

Objective

Obesity and excess adiposity are leading causes of metabolic and cardiovascular morbidity and mortality. Early identification of individuals at risk is key for preventive strategies. We examined the relationship between infant body composition (0–2 years of age) and later (>2 years) health outcomes using a systematic review.

Design

We preregistered the study on PROSPERO (ID 288013) and searched Embase, PubMed and Cochrane databases for English language publications using the Medical Subject Headings (MeSH) terms ‘infant’ and ‘body composition’ and ‘risk’ between January 1946 and February 2022. We included studies which assessed infant body composition using predetermined in vivo methods other than body mass index (BMI).

Results

We identified 6015 articles. After abstract screening to assess eligibility, we reviewed 130 full text publications. 30 were included in the final assessment and narrative synthesis. Meta-analysis was not possible due to heterogeneity of results. All 30 studies were of high quality and reported associations between infant body composition and 19 different health outcomes after 2 years of age. Outcome measurements ranged from 2 years to 16 years. The strongest associations were found between infant fat mass and later fat mass (7 studies), and later BMI (5 studies). For 11 of the outcomes assessed, there was no relationship to infant adiposity detected.

Conclusions

Current evidence, from a small number of studies, suggests a positive association between infant adiposity and future adiposity or BMI, but the validity of infant body composition as a biomarker of future health remains inconclusive. Carefully designed, standardised studies are required to identify the value of infant body composition for predicting later health.

Trial registration

PROSPERO: 288013
Migrated coronary stent into the left internal carotid artery: a rescue technique
Authors: Kühn Anna Luisa , Singh Jasmeet , Puri Ajit S
Published: November 2023

Coronary stent dislodgement and migration is a rare phenomenon that can potentially result in life-threatening complications. We encountered the unusual case of a coronary artery stent that stripped from its delivery balloon and embolised into the left internal carotid artery during percutaneous coronary intervention. Such an event is a stressful experience for the interventional cardiologist but also an uncommonly encountered situation for a neurointerventionalist whose expertise may be sought to help navigate the situation. Planning the interventional approach and taking into consideration the tools available as well as potential complications is crucial to maximise the chances of best possible outcome for the patient. We were able to retrieve the stent safely and successfully, but, at the same time, we were prepared to manage any adverse events in the best way possible.
Strategic donor behaviour and country vulnerability in health aid transitions
Authors: Mao Wenhui , McDade Kaci Kennedy , Ogbuoji Osondu , Yamey Gavin , Bermeo Sarah Blodgett
Published: November 2023

Background

When countries reach the middle-income threshold, many multilateral donors, including Gavi, the Vaccine Alliance (Gavi), begin to withdraw their official development assistance (ODA), known as graduation. We hypothesised that bilateral donors might follow Gavi’s lead, except in countries where they have strategic interests. We aim to understand how bilateral donors behave after a recipient country graduates from Gavi support and how bilateral donors might treat Gavi support countries differently, based on ‘strategic interest’. We also aim to identify countries that were more vulnerable to ‘simultaneous’ transitions and financial cliffs after Gavi transition.

Methods

This is an observational dyadic analysis using longitudinal data. We collected country-level data on 77 Gavi-eligible countries between 2009 and 2018 and paired donor and recipient country in a specific year to conduct dyadic analysis. We included Gavi graduation status and Gavi disbursement as explanatory variables. We controlled for (1) donor–recipient relationship variables that represent potential strategic relationships (eg, distance between donor and recipient country) and (2) recipient-level characteristics (eg, population, income). We used Odinary Least Squares regression, Tobit and two-part model in Stata SE 15.0.

Findings

We found a country would receive $3.1 million less all sector ODA from a bilateral donor, and $0.6 million less health ODA, after they graduate from Gavi. For every additional 1% ODA a country would receive from Gavi, it would receive 0.14% more ODA and 0.16% more health ODA from individual bilateral donors. Gavi’s graduation status or disbursement brought more change in percentage term to health ODA than to total ODA. Additionally, Gavi’s graduation was observed to have a larger negative impact on bilateral ODA in the longer term. Countries that sent more migrants, had been colonised, and received more US military assistance tended to receive more ODA. There are similarities and differences across different donors and bilateral donors tend to provide more ODA to nearby countries and countries receiving fewer exports from the donor. We found that former colonies did not see a decline in aid after Gavi graduation.

Conclusion

Bilateral donors behave in a similar manner to Gavi when it comes to funding health systems in low and middle-income countries. Therefore, some countries may be at risk of losing donor resources for health from a multitude of sources around the same time. However, countries that have a strategic interest in bilateral donors may be spared from such funding cliffs. This research has important implications for global health donors’ funding policies and approaches in addition to recipient countries’ transition planning.
The contribution of active case detection to malaria elimination in Thailand
Authors: Kitchakarn Suravadee , Naowarat Sathapana , Sudathip Prayuth , Simpson Hope , Stelmach Rachel , Suttiwong Chalita , Puengkasem Sombat , Chanti Worawut , Gopinath Deyer , Kanjanasuwan Jerdsuda , Tipmontree Rungrawee , Pinyajeerapat Niparueradee , Sintasath David , Bisanzio Donal , Shah Jui A
Published: November 2023

Introduction

Thailand’s malaria surveillance system complements passive case detection with active case detection (ACD), comprising proactive ACD (PACD) methods and reactive ACD (RACD) methods that target community members near index cases. However, it is unclear if these resource-intensive surveillance strategies continue to provide useful yield. This study aimed to document the evolution of the ACD programme and to assess the potential to optimise PACD and RACD.

Methods

This study used routine data from all 6 292 302 patients tested for malaria from fiscal year 2015 (FY15) to FY21. To assess trends over time and geography, ACD yield was defined as the proportion of cases detected among total screenings. To investigate geographical variation in yield from FY17 to FY21, we used intercept-only generalised linear regression models (binomial distribution), allowing random intercepts at different geographical levels. A costing analysis gathered the incremental financial costs for one instance of ACD per focus.

Results

Test positivity for ACD was low (0.08%) and declined over time (from 0.14% to 0.03%), compared with 3.81% for passive case detection (5.62%–1.93%). Whereas PACD and RACD contributed nearly equal proportions of confirmed cases in FY15, by FY21 PACD represented just 32.37% of ACD cases, with 0.01% test positivity. Each geography showed different yields. We provide a calculator for PACD costs, which vary widely. RACD costs an expected US$226 per case investigation survey (US$1.62 per person tested) or US$461 per mass blood survey (US$1.10 per person tested).

Conclusion

ACD yield, particularly for PACD, is waning alongside incidence, offering an opportunity to optimise. PACD may remain useful only in specific microcontexts with sharper targeting and implementation. RACD could be narrowed by defining demographic-based screening criteria rather than geographical based. Ultimately, ACD can continue to contribute to Thailand’s malaria elimination programme but with more deliberate targeting to balance operational costs.