bluuebunny/crossref_metadata_2025 huggingface dataset:
Salmonella
associated with agricultural animals exhibit diverse evolutionary rates and show evidence of recent clonal expansion
Authors: Chen Ruixi , Yang Linghuan , Pajor Magdalena S. , Wiedmann Martin , Orsi Renato H.
Published: September 2024

Most foodborne salmonellosis outbreaks are linked to agricultural animal products with a few serovars accounting for most
Salmonella
isolated from specific animal products, suggesting an adaptation to the corresponding animal hosts and their respective environments. Here, we utilized whole-genome sequence (WGS) data to analyze the evolution and population genetics of seven serovars frequently isolated from ground beef (Montevideo, Cerro, and Dublin), chicken (Kentucky, Infantis, and Enteritidis), and turkey (Reading) in the United States. In addition, publicly available metadata were used to characterize major clades within each serovar with regard to public health significance. Except for Dublin, all serovars were polyphyletic, comprising 2–6 phylogenetic groups. Further partitioning of the phylogenies identified 25 major clades, including 12 associated with animal or environmental niches. These 12 clades differed in evolutionary parameters (e.g., substitution rates) as well as public health relevant characteristics (e.g., association with human illness, antimicrobial resistance). Overall, our results highlight several critical trends: (i) the
Salmonella
generation time appears to be more dependent on source than serovar and (ii) all serovars contain clades and sub-clades that are estimated to have emerged after the year 1940 and that are enriched for isolates associated with humans, agricultural animals, antimicrobial resistance (AMR), and/or specific geographical regions. These findings suggest that serotyping alone does not provide enough resolution to differentiate isolates that may have evolved independently, present distinct geographic distribution and host association, and possibly have distinct public health significance.

IMPORTANCE

Non-typhoidal
Salmonella
are major foodborne bacterial pathogens estimated to cause more than one million illnesses, thousands of hospitalizations, and hundreds of deaths annually in the United States. More than 70% of
Salmonella
outbreaks in the United States have been associated with agricultural animals. Certain serovars include persistent strains that have repeatedly contaminated beef, chicken, and turkey, causing outbreaks and sporadic cases over many years. These persistent strains represent a particular challenge to public health, as they are genetically clonal and widespread, making it difficult to differentiate distinct outbreak and contamination events using whole-genome sequence (WGS)-based subtyping methods (e.g., core genome allelic typing). Our results indicate that a phylogenetic approach is needed to investigate persistent strains and suggest that the association between a
Salmonella
serovar and an agricultural animal is driven by the expansion of clonal subtypes that likely became adapted to specific animals and associated environments.
LincR-PPP2R5C deficiency enhancing the fungicidal activity of neutrophils in pulmonary cryptococcosis is linked to the upregulation of IL-4
Authors: Yang Chen , Gong Ying , Liu Shan , Sun Chunan , Wang Ting , Chen Xin , Liu Wei , Zhang Xia , Yang Yonglin , Zhang Mingshun
Published: September 2024

Pulmonary cryptococcosis is a common complication in immunocompromised patients. In a mouse model of pulmonary cryptococcosis,
Cryptococcus neoformans
induces a type 2 immune response that is detrimental to host protection. Long non-coding RNAs (lncRNAs) have emerged as key players in the pathogenesis of infectious diseases. However, the roles and mechanisms of lncRNAs in fungal infection are largely elusive. In the present study, we aimed to explore the roles of LincR-PPP2R5C in pulmonary cryptococcosis. We observed an increase in the level of LincR-PPP2R5C in the lung tissues of C57BL/6J mice after tracheal infection with
C. neoformans
. Subsequently, we intratracheally infected LincR-PPP2R5C knockout (KO) mice and wild-type mice with
C. neoformans
. LincR-PPP2R5C deficiency mitigates
C. neoformans
infection, which can be demonstrated by extending survival time and decreasing fungal burden in the lung. In the lung tissues of infected LincR-PPP2R5C KO mice, there was a notable increase in the levels of type 2 cytokines [interleukin (IL)-4 and IL-5] and an increase in the number of neutrophils in both the lung tissue and bronchoalveolar lavage fluid. Mechanistically, the lack of LincR-PPP2R5C results in increased protein phosphatase 2A phosphorylation, thereby enhancing the fungicidal activity of neutrophils against
Cryptococcus neoformans
, with IL-4 playing a synergistic role in this process. Overall, LincR-PPP2R5C deficiency mitigated pulmonary cryptococcosis by increasing the fungicidal activity of neutrophils, which was associated with increased IL-4 levels. Our study presented specific evidence of the role of host-derived lncRNAs in the regulation of
C. neoformans
infection.

IMPORTANCE

Pulmonary cryptococcosis is a human fungal disease caused by
Cryptococcus neoformans
, which is common not only in immunocompromised individuals but also in patients with normal immune function. Therefore, studying the control mechanisms of pulmonary cryptococcosis is highly important. Here, we demonstrated that the deletion of LincR-PPP2R5C leads to increased killing of
C. neoformans
by neutrophils, thereby reducing pulmonary cryptococcal infection. These findings will greatly enhance our understanding of the mechanisms by which lncRNAs regulate the pathogenesis of
C. neoformans
, facilitating the use of lncRNAs in pulmonary cryptococcosis therapy.
Development of novel multi-protein chimeric immunogens that protect against infection with the Lyme disease agent,
Borreliella burgdorferi
Authors: O’Bier Nathaniel S. , Camire Andrew C. , Patel Dhara T. , Billingsley John S. , Hodges Kelly R. , Marconi Richard T.
Published: September 2024

Lyme disease is the most common tick-borne disease in North America. A vaccine for use in humans is not available. Here, we detail the development of two chimeric vaccine antigens, BAF and Chv2M. BAF elicits Abs that target proteins and protein variants produced by
Borreliella
species in ticks (OspB and OspA) and mammals (FtlA/B). OspB serves as the backbone structure for the BAF chimeric. Two OspA
221-240
epitope-containing domain (ECD) variants (#A1 and #A15) were inserted into a loop in OspB. The N-terminal region of the FtlA protein was joined to the C-terminus of the chimeric. The second chimeric, Chv2M, consists of L5 (loop 5) and H5 (helix 5) ECDs derived from diverse OspC proteins.
Borreliella
species produce OspC upon exposure to the bloodmeal and during early infection in mammals. Here, we demonstrate that BAF and Chv2M are potent immunogens that elicit Abs that bind to each component protein (FtlA, FtlB, OspB, and multiple OspA and OspC variants). Anti-BAF and anti-Chv2M Abs kill
Borreliella burgdorferi
strains through Ab-mediated complement-dependent and complement-independent mechanisms. Eighty percent (32/40) of mice that received a three-dose vaccine regimen were protected from infection with
B. burgdorferi
B31. Efficacy increased to 90% (18/20) when the amount of Chv2M was increased in the third vaccine dose. Readouts for infection were
flaB
PCR and seroconversion to VlsE. This study establishes proof of principle for a chimeric immunogen vaccine formulation that elicits Abs to multiple targets on the
B. burgdorferi
cell surface produced during tick and mammalian stages of the enzootic cycle.

IMPORTANCE

Lyme disease is a growing public health threat across parts of the Northern Hemisphere. Regions that can support sustained tick populations are expanding, and the incidence of tick-borne diseases is increasing. In light of the increasing risk of Lyme disease, effective preventive strategies are needed. Most vaccine development efforts have focused on outer surface protein A, a
Borreliella burgdorferi
protein produced only in ticks. Herein, we describe the development of a novel vaccine formulation consisting of two multivalent chimeric proteins that are immunogenic and elicit antibodies with bactericidal activity that target several cell surface proteins produced by the Lyme disease spirochetes in feeding ticks and mammals. In a broader sense, this study advances efforts to develop custom-designed vaccinogens comprised of epitope-containing domains from multiple proteins.
Deciphering transcript architectural complexity in bacteria and archaea
Authors: Mattick John S. A. , Bromley Robin E. , Watson Kaylee J. , Adkins Ricky S. , Holt Christopher I. , Lebov Jarrett F. , Sparklin Benjamin C. , Tyson Tyonna S. , Rasko David A. , Dunning Hotopp Julie C.
Published: September 2024

RNA transcripts are potential therapeutic targets, yet bacterial transcripts have uncharacterized biodiversity. We developed an algorithm for transcript prediction called tp.py using it to predict transcripts (mRNA and other RNAs) in
Escherichia coli
K12 and E2348/69 strains (Bacteria:gamma-Proteobacteria),
Listeria monocytogenes
strains Scott A and RO15 (Bacteria:Firmicute),
Pseudomonas aeruginosa
strains SG17M and NN2 strains (Bacteria:gamma-Proteobacteria), and
Haloferax volcanii
(Archaea:Halobacteria). From >5 million
E. coli
K12 and >3 million
E. coli
E2348/69 newly generated Oxford Nanopore Technologies direct RNA sequencing reads, 2,487 K12 mRNAs and 1,844 E2348/69 mRNAs were predicted, with the K12 mRNAs containing more than half of the predicted
E. coli
K12 proteins. While the number of predicted transcripts varied by strain based on the amount of sequence data used, across all strains examined, the predicted average size of the mRNAs was 1.6–1.7 kbp, while the median size of the 5′- and 3′-untranslated regions (UTRs) were 30–90 bp. Given the lack of bacterial and archaeal transcript annotation, most predictions were of novel transcripts, but we also predicted many previously characterized mRNAs and ncRNAs, including post-transcriptionally generated transcripts and small RNAs associated with pathogenesis in the
E. coli
E2348/69
LEE
pathogenicity islands. We predicted small transcripts in the 100–200 bp range as well as >10 kbp transcripts for all strains, with the longest transcript for two of the seven strains being the
nuo
operon transcript, and for another two strains it was a phage/prophage transcript. This quick, easy, and reproducible method will facilitate the presentation of transcripts, and UTR predictions alongside coding sequences and protein predictions in bacterial genome annotation as important resources for the research community.

IMPORTANCE

Our understanding of bacterial and archaeal genes and genomes is largely focused on proteins since there have only been limited efforts to describe bacterial/archaeal RNA diversity. This contrasts with studies on the human genome, where transcripts were sequenced prior to the release of the human genome over two decades ago. We developed software for the quick, easy, and reproducible prediction of bacterial and archaeal transcripts from Oxford Nanopore Technologies direct RNA sequencing data. These predictions are urgently needed for more accurate studies examining bacterial/archaeal gene regulation, including regulation of virulence factors, and for the development of novel RNA-based therapeutics and diagnostics to combat bacterial pathogens, like those with extreme antimicrobial resistance.
The interplay between mobilome and resistome in
Staphylococcus aureus
Authors: Contarin Rachel , Drapeau Antoine , François Pauline , Madec Jean-Yves , Haenni Marisa , Dordet-Frisoni Emilie
Published: September 2024

Antibiotic resistance genes (ARGs) in
Staphylococcus aureus
can disseminate vertically through successful clones, but also horizontally through the transfer of genes conveyed by mobile genetic elements (MGEs). Even though underexplored, MGE/ARG associations in
S. aureus
favor the emergence of multidrug-resistant clones, which are challenging therapeutic success in both human and animal health. This study investigated the interplay between the mobilome and the resistome of more than 10,000
S
.
aureus
genomes from human and animal origin. The analysis revealed a remarkable diversity of MGEs and ARGs, with plasmids and transposons being the main carriers of ARGs. Numerous MGE/ARG associations were identified, suggesting that MGEs play a critical role in the dissemination of resistance. A high degree of similarity was observed in MGE/ARG associations between human and animal isolates, highlighting the potential for unrestricted spread of ARGs between hosts. Our results showed that in parallel to clonal expansion, MGEs and their associated ARGs can spread across different strain types sequence types (STs), favoring the evolution of these clones and their adaptation in selective environments. The high variability of MGE/ARG associations within individual STs and their spread across several STs highlight the crucial role of MGEs in shaping the
S. aureus
resistome. Overall, this study provides valuable insights into the complex interplay between MGEs and ARGs in
S. aureus
, emphasizing the need to elucidate the mechanisms governing the epidemic success of MGEs, particularly those implicated in ARG transfer.

IMPORTANCE

The research presented in this article highlights the importance of understanding the interactions between mobile genetic elements (MGEs) and antibiotic resistance genes (ARGs) carried by
Staphylococcus aureus
, a versatile bacterium that can be both a harmless commensal and a dangerous pathogen for humans and animals.
S. aureus
has a great capacity to acquire and disseminate ARGs, enabling efficient adaption to various environmental or clinical conditions. By analyzing a large data set of
S. aureus
genomes, we highlighted the substantial role of MGEs, particularly plasmids and transposons, in disseminating ARGs within and between
S. aureus
populations, bypassing host barriers. Given that multidrug-resistant
S. aureus
strains are classified as a high-priority pathogen by global health organizations, this knowledge is crucial for understanding the complex dynamics of transmission of antibiotic resistance in this species.
Draft genomes of multidrug-resistant
Campylobacter jejuni
and
Campylobacter coli
strains from Brazil representing novel sequence types
Authors: Portes Ana Beatriz , Panzenhagen Pedro , dos Santos Anamaria Mota Pereira , de Jesus Ana Carolina Silva , Ochioni Alan Clavelland , Duque Sheila da Silva , Aburjaile Flávia Figueira , Brenig Bertram , Azevedo Vasco , Conte Junior Carlos Adam
Published: September 2024

Whole-genome sequencing identified three previously unidentified multilocus sequence types of
Campylobacter jejuni
(ST-12332) and
Campylobacter coli
(ST-12333 and ST-12663), harboring resistance genes for multiple antimicrobial classes. The sources of isolation highlight the circulation of resistance strains within animals and humans, emphasizing the need for preventive measures.
Biosynthetic gene clusters from uncultivated soil bacteria of the Atacama Desert
Authors: Andreani-Gerard Constanza M. , Cambiazo Verónica , González Mauricio
Published: September 2024

Soil microorganisms mediate several biological processes through the secretion of natural products synthesized in specialized metabolic pathways, yet functional characterization in ecological contexts remains challenging. Using culture-independent metagenomic analyses of microbial DNA derived directly from soil samples, we examined the potential of biosynthetic gene clusters (BGCs) from six bacterial communities distributed along an altitudinal gradient of the Andes Mountains in the Atacama Desert. We mined 38 metagenome-assembled genomes (MAGs) and identified 168 BGCs. Results indicated that most predicted BGCs were classified as non-ribosomal-peptides (NRP), post-translational modified peptides (RiPP), and terpenes, which were mainly identified in genomes of species from
Acidobacteriota
and
Proteobacteria
phyla. Based on BGC composition according to types of core biosynthetic genes, six clusters of MAGs were observed, three of them with predominance for a single phylum, of which two also showed specificity to a single sampling site. Comparative analyses of accessory genes in BGCs showed associations between membrane transporters and other protein domains involved in specialized metabolism with classes of biosynthetic cores, such as resistance-nodulation-cell division (RND) multidrug efflux pumps with RiPPs and the iron-dependent transporter TonB with terpenes. Our findings increase knowledge regarding the biosynthetic potential of uncultured bacteria inhabiting pristine locations from one of the oldest and driest nonpolar deserts on Earth.

IMPORTANCE

Much of what we know about specialized metabolites in the Atacama Desert, including Andean ecosystems, comes from isolated microorganisms intended for drug development and natural product discovery. To complement research on the metabolic potential of microbes in extreme environments, comparative analyses on functional annotations of biosynthetic gene clusters (BGCs) from uncultivated bacterial genomes were carried out. Results indicated that in general, BGCs encode for structurally unique metabolites and that metagenome-assembled genomes did not show an obvious relationship between the composition of their core biosynthetic potential and taxonomy or geographic distribution. Nevertheless, some members of
Acidobacteriota
showed a phylogenetic relationship with specific metabolic traits and a few members of
Proteobacteria
and
Desulfobacterota
exhibited niche adaptations. Our results emphasize that studying specialized metabolism in environmental samples may significantly contribute to the elucidation of structures, activities, and ecological roles of microbial molecules.
Exploring the vitamin biosynthesis landscape of the human gut microbiota
Authors: Tarracchini Chiara , Lugli Gabriele Andrea , Mancabelli Leonardo , van Sinderen Douwe , Turroni Francesca , Ventura Marco , Milani Christian
Published: September 2024

The human gut microbiota possesses the capacity to synthesize vitamins, especially B group vitamins, which are recognized as indispensable for various biological processes both among members of these bacterial communities and host cells. Accordingly, vitamin production by intestinal commensals has attracted significant interest. Nevertheless, our current understanding of bacterial vitamin synthesis is primarily based on individual genomic and monoculture investigations, therefore not providing an overall view of the biosynthetic potential of complex microbial communities. In the current study, we utilized over 100 bacterial genes known to be involved in the biosynthesis of B group and K vitamins to assess the corresponding vitamin biosynthetic potential of approximately 8,000 human gut microbiomes. Our analyses reveal that host-associated factors, such as age and geographical origin, appear to influence the diversity and abundance of vitamin biosynthetic pathways. Furthermore, we identify gut microbiota members that substantially contribute to these biosynthetic functions at each stage of human life. Interestingly, inference of microbial co-associations and network relationships uncovered the apparent key role played by folate and cobalamin in equilibrium establishment of the infant and adult gut microbial communities, respectively.

IMPORTANCE

Overall, this study expands our understanding of microbe-mediated vitamin biosynthesis in the human gut and may provide potential novel targets to improve availability of these essential micronutrients in the host.
Multi-omics analysis reveals regime shifts in the gastrointestinal ecosystem in chickens following anticoccidial vaccination and
Eimeria tenella
challenge
Authors: Liu Po-Yu , Liaw Janie , Soutter Francesca , Ortiz José Jaramillo , Tomley Fiona M. , Werling Dirk , Gundogdu Ozan , Blake Damer P. , Xia Dong
Published: September 2024

Coccidiosis, caused by
Eimeria
parasites, significantly impacts poultry farm economics and animal welfare. Beyond its direct impact on health,
Eimeria
infection disrupts enteric microbial populations leading to dysbiosis and increases vulnerability to secondary diseases such as necrotic enteritis, caused by
Clostridium perfringens
. The impact of
Eimeria
infection or anticoccidial vaccination on host gastrointestinal phenotypes and enteric microbiota remains understudied. In this study, the metabolomic profiles and microbiota composition of chicken caecal tissue and contents were evaluated concurrently during a controlled experimental vaccination and challenge trial. Cobb500 broilers were vaccinated with a
Saccharomyces cerevisiae
-vectored anticoccidial vaccine and challenged with 15,000
Eimeria tenella
oocysts. Assessment of caecal pathology and quantification of parasite load revealed correlations with alterations to caecal microbiota and caecal metabolome linked to infection and vaccination status. Infection heightened microbiota richness with increases in potentially pathogenic species, while vaccination elevated beneficial
Bifidobacterium
. Using a multi-omics factor analysis, data on caecal microbiota and metabolome were integrated and distinct profiles for healthy, infected, and recovering chickens were identified. Healthy and recovering chickens exhibited higher vitamin B metabolism linked to short-chain fatty acid-producing bacteria, whereas essential amino acid and cell membrane lipid metabolisms were prominent in infected and vaccinated chickens. Notably, vaccinated chickens showed distinct metabolites related to the enrichment of sphingolipids, important components of nerve cells and cell membranes. Our integrated multi-omics model revealed latent biomarkers indicative of vaccination and infection status, offering potential tools for diagnosing infection, monitoring vaccination efficacy, and guiding the development of novel treatments or controls.

IMPORTANCE

Advances in anticoccidial vaccines have garnered significant attention in poultry health management. However, the intricacies of vaccine-induced alterations in the chicken gut microbiome and its subsequent impact on host metabolism remain inadequately explored. This study delves into the metabolic and microbiotic shifts in chickens post-vaccination, employing a multi-omics integration analysis. Our findings highlight a notable synergy between the microbiome composition and host-microbe interacted metabolic pathways in vaccinated chickens, differentiating them from infected or non-vaccinated cohorts. These insights pave the way for more targeted and efficient approaches in poultry disease control, enhancing both the efficacy of vaccines and the overall health of poultry populations.
VSV infection and LPS treatment alter serum bile acid profiles, bile acid biosynthesis, and bile acid receptors in mice
Authors: Li Yamei , Luo Yan , Wang Chao , Xu Lei , Dai Xinhua , An Yunfei , He Lin , Zeng Dongmei , Bai Yangjuan , Zhang Hua
Published: September 2024

Pathogen infections remain a significant public health problem worldwide. Accumulating evidence regarding the crosstalk between bile acid (BA) metabolism and immune response reveals that BA metabolism regulates host immunity and microbial pathogenesis, making it an attractive target for disease prevention and infection control. However, the effect of infection on circulating BA profiles, the biosynthesis-related enzymes, and their receptors remains to be depicted. Here, we investigated the effect of viral (vesicular stomatitis virus, VSV) and bacterial (lipopolysaccharide, LPS) infections on BA metabolism and signaling. Infection models were successfully established by intraperitoneally injecting VSV and LPS, respectively. VSV and LPS injection significantly changed the circulating BA profiles, with highly increased levels of taurine-conjugated BAs and significant decreases in unconjugated BAs. Consistent with the decreased levels of circulating cholic acid (CA) and chenodeoxycholic acid (CDCA), the expression of BA biosynthesis-related rate-limiting enzymes (
Cyp7a1
,
Cyp27a1
,
Cyp8b1,
and
Hsd3b7
) were significantly reduced. Furthermore, hepatic and pulmonary BA receptors (BARs) expression varied in different infection models. LPS treatment had an extensive impact on tested hepatic and pulmonary BARs, resulting in the upregulation of TGR5, S1PR2, and VDR, while VSV infection only promoted VDR expression. Our study provides insights into the involvement of BA metabolism in the pathophysiology of infection, which may provide potential clues for targeting BA metabolism and BAR signaling to boost innate immunity and control infection.

IMPORTANCE

This study focuses on the crosstalk between bile acid (BA) metabolism and immune response in VSV infection and LPS treatment models and depicts the effect of infection on circulating BA profiles, the biosynthesis-related enzymes, and their receptors. These findings provide insights into the effect of infection on BA metabolism and signaling, adding a more comprehensive understanding to the relationship between infection, BA metabolism and immune responses.
Trends in sex differences in neurodevelopmental outcomes among extremely preterm infants
Authors: Boghossian Nansi S , Mack Nicole A , Bell Edward F , Tan Sylvia , Stoll Barbara J , Rysavy Matthew A , Ambalavanan Namasivayam , Tyson Jon E , Das Abhik , Hintz Susan R
Published: September 2024

Objective

To examine whether changes in survival without moderate or severe neurodevelopmental impairment (NDI) at 18–26 months’ corrected age from 1999 to 2018 differed between male and female infants.

Design

This retrospective cohort study used data from the NICHD Neonatal Research Network hospitals. Robust Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% CIs for survival without moderate or severe NDI between males and females. Interactions between sex and time were assessed to evaluate temporal differences in the outcome by sex. Variables adjusted for included centre, maternal age, ethnicity/race, gestational age and small for gestational age.

Patients

Inborn infants with gestational age of 22–26 weeks at NICHD Neonatal Research Network hospitals from 1999 to 2018.

Main outcome measure

Change over time in survival without moderate or severe NDI at 18–26 months’ corrected age between male and female infants.

Results

Of 26 307 infants, 13 045 (49.6%) were male. Survival without moderate or severe NDI declined for both sexes over time, from 32.9% to 30.6% for males and from 47.4% to 40.0% for females, between 1999–2003 and 2014–2018. Males were less likely than females to survive without moderate or severe NDI (aRR=0.80; 95% CI 0.78 to 0.83). Changes in survival without moderate or severe NDI did not differ between males and females.

Conclusion

There were no differential changes in survival without moderate or severe NDI between male and female infants.
Use of CFTR modulators in pregnancy: new information for neonatal, paediatrics and midwifery teams
Authors: Khan Haji Sheeraz , Tran Paula
Published: September 2024

Cystic fibrosis (CF) is common, multisystem, life-limiting genetic condition, predominantly in the Caucasian population. There have been recent advances in the management of CF, in particular in the last 5 years following approval of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators by the National Health Service (NHS) for use in people with CF (pwCF).

Traditionally, almost 40% of female patients with CF (fwCF) and over 95% of male patients with CF (mwCF) have issues with subfertility or infertility. CFTR modulators have transformed the lives of pwCF who have the specific genetic variants that respond to the treatment.

Women taking CFTR modulators, particularly highly effective CFTR modulators (elexacaftor, tezacaftor and ivacaftor), have shown resolution of infertility and successful pregnancies without fertility treatment. At present male patients taking CFTR modulators have not shown improvement in infertility. Unplanned pregnancies are on the increase in fwCF. fwCF have had significantly improved general health when taking CFTR modulators. Subsequently many fwCF now become pregnant and choose to continue their pregnancies to term, with positive outcomes.

Clinical and biochemical status of the newborn babies with CF, who are born to fwCF on CFTR modulators, can be very different when compared with the other babies with CF who are unexposed to CFTR modulators in utero.

New opportunities bring new challenges. This review highlights how infants exposed to CFTR modulators in utero can be affected, and suggests how they should be monitored.
Cumulative live birth rate of a blastocyst versus cleavage stage embryo transfer policy during in vitro fertilisation in women with a good prognosis: multicentre randomised controlled trial
Authors: Cornelisse Simone , Fleischer Kathrin , van der Westerlaken Lucette , de Bruin Jan-Peter , Vergouw Carlijn , Koks Carolien , Derhaag Josien , Visser Jantien , van Echten-Arends Jannie , Slappendel Els , Arends Brigitte , van der Zanden Moniek , van Dongen Angelique , Brink-van der Vlugt Janneke , de Hundt Marcella , Curfs Max , Verhoeve Harold , Traas-Hofmans Maaike , Wurth Yvonne , Manger Petra , Pieterse Quirine , Braat Didi , van Wely Madelon , Ramos Liliana , Mastenbroek Sebastiaan
Published: September 2024

Objectives

To evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and perinatal complications is increased compared with cleavage stage embryo transfers during in vitro fertilisation (IVF) treatment.

Design

Multicentre randomised controlled trial.

Setting

21 hospitals and clinics in the Netherlands, 18 August 2018 to 17 December 2021.

Participants

1202 women with at least four embryos available on day 2 after oocyte retrieval were randomly assigned to either blastocyst stage embryo transfer (n=603) or cleavage stage embryo transfer (n=599).

Interventions

In the blastocyst group and cleavage group, embryo transfers were performed on day 5 and day 3, respectively, after oocyte retrieval, followed by cryopreservation of surplus embryos. Analysis was on an intention-to-treat basis, with secondary analyses as per protocol.

Main outcome measures

The primary outcome was the cumulative live birth rate per oocyte retrieval, including results of all frozen-thawed embryo transfers within a year after randomisation. Secondary outcomes included cumulative rates of pregnancy, pregnancy loss, and live birth after fresh embryo transfer, number of embryo transfers needed, number of frozen embryos, and obstetric and perinatal outcomes.

Results

The cumulative live birth rate did not differ between the blastocyst group and cleavage group (58.9% (355 of 603)
v
58.4% (350 of 599; risk ratio 1.01, 95% confidence interval (CI) 0.84 to 1.22). The blastocyst group showed a higher live birth rate after fresh embryo transfer (1.26, 1.00 to 1.58), lower cumulative pregnancy loss rate (0.68, 0.51 to 0.89), and lower mean number of embryo transfers needed to result in a live birth (1.55
v
1.82; P<0.001). The incidence of moderate preterm birth (32 to <37 weeks) in singletons was higher in the blastocyst group (1.87, 1.05 to 3.34).

Conclusion

Blastocyst stage embryo transfers resulted in a similar cumulative live birth rate to cleavage stage embryo transfers in women with at least four embryos available during IVF treatment.

Trial registration

International Clinical Trial Registry Platform NTR7034.
Does socioeconomic status modify how individuals perceive or describe their own health? An assessment of reporting heterogeneity in the Health Survey for England
Authors: Fforde Rosanna , Parsons Nicholas , Oyebode Oyinlola
Published: September 2024

Background

Self-reported health (SRH) is widely used as a proxy for health status; it is a simple, holistic measure of health and has been associated with other health outcomes. However, variation in these associations has been found by subgroup, leaving open the possibility of systematic reporting differences, including by socioeconomic status.

Methods

Using data from the 2017 and 2018 waves of the Health Survey for England, we assessed the relationship between deprivation quintile and SRH using multiple linear regression models for EQ-5D score, a health-related quality of life measure. Reporting heterogeneity between deprivation quintiles was assessed by the significance of model interaction terms. Analyses were stratified by sex and accounted for age group, ethnicity, marital status and religion (females only).

Results

Significant interactions were found between deprivation quintile and SRH in the models for EQ-5D score for participants reporting poor health in the two most deprived quintiles, with coefficients ranging from –0.041 to –0.098. The largest differences were in the second most deprived quintile for men (–0.075, 95% CI: –0.110 to –0.040, p<0.001) and the most deprived quintile for women (–0.098, 95% CI: –0.128 to –0.067, p<0.001). Secondary analyses using body mass index as the response variable, for models structured in a similar way to those for EQ-5D, found no significant interaction terms between deprivation quintile and SRH.

Conclusions

This analysis suggests that people from more deprived areas who report themselves to be in poor health may have worse health, as measured by EQ-5D, than those from less deprived areas. This could lead to an underestimation of health inequalities, including in measures, such as healthy life expectancy in England, that incorporate SRH data.
How do emergency departments respond to ambulance pre-alert calls? A qualitative exploration of the management of pre-alerts in UK emergency departments
Authors: Long Jaqui , Sampson Fiona C , Coster Joanne , O’Hara Rachel , Bell Fiona , Goodacre Steve
Published: September 2024

Background

Calls to emergency departments (EDs) from ambulances to alert them to a critical case being transported to that facility that requires a special response (‘pre-alerts’) have been shown to improve outcomes for patients requiring immediate time-critical treatment (eg, stroke). However, little is known about their usefulness for other patients and the processes involved in ED responses to them. This study aimed to understand how pre-alerts influence patient care in the ED.

Methods

We undertook non-participant observation (162 hours, 143 pre-alerts) and semi-structured interviews with staff (n=40) in six UK EDs between August 2022 and April 2023 focusing on how ED staff respond to pre-alert calls and what influences their response. Observation notes and interview transcripts were imported into NVivo and analysed using a thematic approach.

Results

Pre-alert calls involved significant time and resources for ED staff but they were valued as they enabled staff to prepare for a patient’s arrival (practically and psychologically). High demand and handover delays at ED created additional pre-alerts due to ambulance clinician concerns about the impact of long waits on patients.

Despite the risk of pre-alert fatigue from calls for patients considered not to require a special response, ED clinicians appreciated timely pre-alert information, perceiving a higher risk from underalerting than overalerting. Variation in ED response was influenced by individual and organisational factors, particularly the resources available at the time of pre-alert. Unclear ED processes for receiving, documenting and sharing information about pre-alerts increased the risk of information loss.

Conclusion

Improving processes for receiving and sharing pre-alert information may help ED clinicians prepare appropriately for incoming patients. Alternative routes for ambulance clinicians to seek advice on borderline pre-alert patients may help to improve the appropriateness of pre-alerts.
Impact of double stent retriever configuration on first-pass effect in stroke: a multicenter study
Authors: Pérez-García Carlos , Castaño Miguel , Llibre Juan Carlos , Vargas Luis , López-Frías Alfonso , Rosati Santiago , López Jose Luis , Venegas Jesus , González Eva , Fondevila Jon , Espinosa de Rueda Mariano , Zamarro Joaquín , Baldi Sebastián , Díaz Teresa , de la Rosa Carmen , Chaviano Grajera Juan , Ballenilla Marco Federico , Cuba Victor , Muñoz Olmedo José M , Mendez Jose Carlos , Remollo Sebastian , Bermejo Rebeca , Morales Edison , Gómez-Escalonilla Carlos , Moreu Manuel
Published: September 2024

Background

Efficient recanalization of occluded cerebral arteries is crucial in the treatment of acute ischemic stroke. Double stent retrievers have shown the potential to enhance the rates of recanalization on the first pass. This study aims to evaluate the efficacy and safety of the double stent retriever technique and the predictors of achieving first-pass effect in patients with acute ischemic stroke.

Methods

This prospective multicenter study involved 209 patients from 16 comprehensive stroke centers in Spain. Patients with occlusions in the anterior circulation were treated using the Aperio Hybrid double stent retriever. The study examined various deployment techniques, including simultaneous and sequential deployment and stent configurations, comparing the Y-shaped and parallel configurations.

Results

The double stent retriever technique achieved a first-pass effect in 72.7% of cases and a final successful recanalization rate of 99.5%. The Y-shaped configuration was significantly associated with higher recanalization rates on the first pass (OR 2.59, 95% CI 1.18 to 5.68, P=0.02). Procedural complications were mild to moderate in 6.7% and severe in 1.5% of cases, with symptomatic intracranial hemorrhage occurring in 3.3% of patients. At 3 months follow-up, 57.2% of patients achieved a good clinical outcome, with a mortality rate of 15.1%.

Conclusion

The findings support the efficacy of the double stent retriever technique, particularly the Y-shaped configuration, in achieving high recanalization rates on the first pass with an acceptable safety profile. This technique may offer clinical benefits for future acute ischemic stroke treatment protocols.
Is speech function lateralised in the basal ganglia? Evidence from de novo Parkinson’s disease
Authors: Rusz Jan , Dusek Petr , Tykalova Tereza , Novotny Michal , Illner Vojtech , Simek Michal , Kouba Tomas , Kryze Petr , Zogala David , Ruzicka Evzen , Sousa Mário , Jorge Adriana , Nef Tobias , Krack Paul
Published: September 2024

Background

Research on the possible influence of lateralised basal ganglia dysfunction on speech in Parkinson’s disease is scarce. This study aimed to compare speech in de-novo, drug-naive patients with Parkinson’s disease (PD) with asymmetric nigral dopaminergic dysfunction, predominantly in either the right or left hemisphere.

Methods

Acoustic analyses of reading passages were performed. Asymmetry of nigral dysfunction was defined using dopamine transporter-single-photon emission CT (DAT-SPECT).

Results

From a total of 135 de novo patients with PD assessed, 47 patients had a lower right and 36 lower left DAT availability in putamen based on DAT-SPECT. Patients with PD with lower left DAT availability had higher dysarthria severity via composite dysarthria index compared with patients with lower right DAT availability (p=0.01).

Conclusion

Our data support the crucial role of DAT availability in the left putamen in speech. This finding might provide important clues for managing speech following deep brain stimulation.
Localisation of function in the brain: a rethink
Authors: O'Sullivan Michael
Published: September 2024

A modular view of brain function dominates the teaching of medical students and clinical psychologists and is implicit in day-to-day clinical practice. This view glosses over a long-standing debate. The extent of one-to-one mappings between region and function remains a controversial topic. For the cortex, localisation of function versus ‘cerebral equipotentiality’ was debated less than 150 years ago, and traces of this debate remain active in systems neuroscience today. The advent of functional brain imaging led to an explosion of evidence on localisation of function studied in vivo, and a gold rush to map an ever-increasing range of ‘functions’. Rapid growth in knowledge was accompanied, to some extent, by a flourishing neuromythology. There are currently few clinical applications of brain mapping techniques, but new areas are emerging. An understanding of the central debate on functional localisation will bring a more nuanced view of problems encountered in clinical practice.
Management of low-level HIV viremia during antiretroviral therapy: Delphi consensus statement and appraisal of the evidence
Authors: Rindi Lorenzo Vittorio , Zaçe Drieda , Compagno Mirko , Colagrossi Luna , Santoro Maria Mercedes , Andreoni Massimo , Perno Carlo Federico , Sarmati Loredana
Published: September 2024

Objective

While antiretroviral therapy (ART) is highly effective, detection of low levels of HIV-1 RNA in plasma is common in treated individuals. Given the uncertainties on the topic, we convened a panel of experts to consider different clinical scenarios, producing a Delphi consensus to help guide clinical practice.

Methods

A panel of 17 experts in infectious diseases, virology and immunology rated 32 statements related to four distinct scenarios: (1) low-level viremia during stable (≥6 months) first-line ART (≥2 consecutive HIV-1 RNA measurements 50–500 copies/mL); (2) a viral blip during otherwise suppressive ART (a HIV-1 RNA measurement 50–1000 copies/mL with adjacent measurements <50 copies/mL); (3) low-level viral rebound during previously suppressive ART (≥2 consecutive HIV-1 RNA measurements 50–500 copies/mL); (4) residual viremia during suppressive ART (persistent HIV-1 RNA quantification below 50 copies/mL). A systematic review, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement, informed the 32 statements. The Delphi procedure was modified to include two voting rounds separated by a moderated group discussion. Grading of Recommendations, Assessment, Development, and Evaluations-based recommendations were developed.

Results

Overall, 18/32 statements (56.2%) achieved a strong consensus, 3/32 (9.4%) achieved a moderate consensus and 11/32 (34.4%) did not achieve a consensus. Across the four scenarios, the panel unanimously emphasised the importance of implementing specific interventions prior to considering therapy changes, including assessing adherence, testing for genotypic drug resistance and scheduling more frequent follow-up visits. Strategies indicated in selected circumstances included therapeutic drug monitoring, quantifying total HIV-1 DNA and evaluating concomitant chronic infections.

Conclusions

While acknowledging the many uncertainties about source, significance and optimal management of low-level viremia during ART, the findings provide insights to help harmonise clinical practice. There is a need for well-designed randomised studies assessing different interventions to manage low-level viremia and future research regarding its definition.
Marine migration, thermal habitat use and feeding habits of Arctic charr (Salvelinus alpinus) in SW Greenland
Authors: Davidsen J.G. , Eldøy S.H. , Piper A.T. , Moccetti C. , Brodersen J. , Whoriskey F. , Power M.
Published: September 2024

Climate change is altering northern coastal aquatic habitats, especially in fjords. Data on current ecosystem structure and biodiversity in many northern fjord and coastal ecosystems, especially for Greenland, are lacking. We used acoustic telemetry combined with stable isotope analyses in a southwest Greenland fjord to investigate marine migrations, marine, and freshwater thermal habitat use, and the marine feeding habits of 80 acoustically tagged Arctic charr over one year. During summer, most Arctic charr occupied the inner fjord. Models of Arctic charr thermal habitat use suggested higher experienced water temperatures in the inner compared to outer fjord (estimated 1.59 °C difference) during tagged charr mean 70-day (SD = 14 days) residencies. During February and March, non-migratory individuals used warmer waters (+0.56 °C higher) than fish that ultimately migrated to sea, suggesting that over-wintering habitat use patterns influenced migration tactics. Stable isotope mixing model analysis indicated that Arctic charr fed mainly on capelin, marine gammarids, and three-spine sticklebacks. The results provide a contemporary baseline for assessing predictions of potential changes in the ecology of Arctic charr in SW Greenland fjords.
Distinct patterns of satDNA distribution in holocentric chromosomes of spike-sedges (Eleocharis, Cyperaceae)
Authors: Souza Thaíssa Boldieri de , Parteka Letícia Maria , Kuo Yi-Tzu , Nascimento Thiago , Schubert Veit , Pedrosa-Harand Andrea , Marques André , Houben Andreas , Vanzela André Luís Laforga
Published: September 2024

Eleocharis R. Br. (Cyperaceae) species are known for having holocentric chromosomes, which enable rapid karyotype differentiation. High intra- and interspecific variations in chromosome numbers and genome sizes are documented for different Eleocharis species, frequently accompanied by fluctuations in the repetitive DNA fraction. However, a lack of detailed analysis has hampered a better understanding of the interplay between holocentricity and repetitive DNA evolution in this genus. In our study, we confirmed the holocentricity of Eleocharis chromosomes by immunostaining against the kinetochore protein KNL1 and the cell-cycle dependent posttranslational modifications histone H2AThr121ph and H3S10ph. We further studied the composition and chromosomal distribution of the main satellite DNA repeats found in the newly sequenced species Eleocharis maculosa, Eleocharis geniculata, Eleocharis parodii, Eleocharis elegans, and Eleocharis montana. Five of the six satellites discovered were arranged in clusters, while EmaSAT14 was distributed irregularly along the chromatid length in a line-like manner. EmaSAT14 monomers were present in a few copies in few species across the Eleocharis phylogenetic tree. Nonetheless, they were accumulated within a restricted group of Maculosae series, subgenus Eleocharis. The data indicates that the amplification and line-like distribution of EmaSAT14 along chromatids may have occurred recently within a section of the genus.
Bulk-induced gravitational waves on braneworld wormhole
Authors: Alias Anuar , Yusuff Imran , Hoh Siew Yan
Published: September 2024

Gravitational waves result from various spacetime-perturbing events which are due to various kinds of motions and changing distributions of mass. Most studies on the source of gravitational waves were derived from the dynamic character of two binary compacted massive objects such as black holes and neutron stars, therefore gravitational waves which originated from a single event source would be of interest. In this paper, we derive the stress–energy tensor (SET) of a braneworld wormhole and demonstrate how the bulk-induced gravitational waves influence the SET of the wormhole. Thus, this study not only suggests a single source of gravitational waves, but also proves the existence of higher dimensional space by providing a formulation, namely, the SET at the wormhole throat affected by the bulk-induced gravitational waves.