bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial central carbon metabolism in a tidal freshwater marsh and an upland mixed conifer soil under oxic and anoxic conditions
Authors: Martinez Ayla , Dijkstra Paul , Megonigal Patrick , Hungate Bruce A.
Published: May 2024

The central carbon (C) metabolic network is responsible for most of the production of energy and biosynthesis in microorganisms and is therefore key to a mechanistic understanding of microbial life in soil communities. Many upland soil communities have shown a relatively high C flux through the pentose phosphate (PP) or the Entner-Doudoroff (ED) pathway, thought to be related to oxidative damage control. We tested the hypothesis that the metabolic organization of the central C metabolic network differed between two ecosystems, an anoxic marsh soil and oxic upland soil, and would be affected by altering oxygen concentrations. We expected there to be high PP/ED pathway activity under high oxygen concentrations and in oxic soils and low PP/ED activity in reduced oxygen concentrations and in marsh soil. Although we found high PP/ED activity in the upland soil and low activity in the marsh soil, lowering the oxygen concentration for the upland soil did not reduce the relative PP/ED pathway activity as hypothesized, nor did increasing the oxygen concentration in the marsh soil increase the PP/ED pathway activity. We speculate that the high PP/ED activity in the upland soil, even when exposed to low oxygen concentrations, was related to a high demand for NADPH for biosynthesis, thus reflecting higher microbial growth rates in C-rich soils than in C-poor sediments. Further studies are needed to explain the observed metabolic diversity among soil ecosystems and determine whether it is related to microbial growth rates.

IMPORTANCE

We observed that the organization of the central carbon (C) metabolic processes differed between oxic and anoxic soil. However, we also found that the pentose phosphate pathway/Entner-Doudoroff (PP/ED) pathway activity remained high after reducing the oxygen concentration for the upland soil and did not increase in response to an increase in oxygen concentration in the marsh soil. These observations contradicted the hypothesis that oxidative stress is a main driver for high PP/ED activity in soil communities. We suggest that the high PP/ED activity and NADPH production reflect higher anabolic activities and growth rates in the upland soil compared to the anaerobic marsh soil. A greater understanding of the molecular and biochemical processes in soil communities is needed to develop a mechanistic perspective on microbial activities and their relationship to soil C and nutrient cycling. Such an increased mechanistic perspective is ecologically relevant, given that the central carbon metabolic network is intimately tied to the energy metabolism of microbes, the efficiency of new microbial biomass production, and soil organic matter formation.
Identifying components of the
Shewanella
phage LambdaSo lysis system
Authors: Thöneböhn Svenja , Fischer Dorian , Kreiling Vanessa , Kemmler Alina , Oberheim Isabella , Hager Fabian , Schmid Nicole E. , Thormann Kai M.
Published: May 2024

Phage-induced lysis of Gram-negative bacterial hosts usually requires a set of phage lysis proteins, a holin, an endopeptidase, and a spanin system, to disrupt each of the three cell envelope layers. Genome annotations and previous studies identified a gene region in the
Shewanella oneidensis
prophage LambdaSo, which comprises potential holin- and endolysin-encoding genes but lacks an obvious spanin system. By a combination of candidate approaches, mutant screening, characterization, and microscopy, we found that LambdaSo uses a pinholin/signal-anchor-release (SAR) endolysin system to induce proton leakage and degradation of the cell wall. Between the corresponding genes, we found that two extensively nested open-reading frames encode a two-component spanin module Rz/Rz1. Unexpectedly, we identified another factor strictly required for LambdaSo-induced cell lysis, the phage protein Lcc6. Lcc6 is a transmembrane protein of 65 amino acid residues with hitherto unknown function, which acts at the level of holin in the cytoplasmic membrane to allow endolysin release. Thus, LambdaSo-mediated cell lysis requires at least four protein factors (pinholin, SAR endolysin, spanin, and Lcc6). The findings further extend the known repertoire of phage proteins involved in host lysis and phage egress.

IMPORTANCE

Lysis of bacteria can have multiple consequences, such as the release of host DNA to foster robust biofilm. Phage-induced lysis of Gram-negative cells requires the disruption of three layers, the outer and inner membranes and the cell wall. In most cases, the lysis systems of phages infecting Gram-negative cells comprise holins to disrupt or depolarize the membrane, thereby releasing or activating endolysins, which then degrade the cell wall. This, in turn, allows the spanins to become active and fuse outer and inner membranes, completing cell envelope disruption and allowing phage egress. Here, we show that the presence of these three components may not be sufficient to allow cell lysis, implicating that also in known phages, further factors may be required.
Group B
Streptococcus
transcriptome when interacting with brain endothelial cells
Authors: Vollmuth Nadine , Bridgers Bailey E. , Armstrong Madelyn L. , Wood Jacob F. , Gildea Abigail R. , Espinal Eric R. , Hooven Thomas A. , Barbieri Giulia , Westermann Alexander J. , Sauerwein Till , Foerstner Konrad U. , Schubert-Unkmeir Alexandra , Kim Brandon J.
Published: May 2024

Bacterial meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when bacteria are able to cross the blood–brain barrier (BBB) or the meningeal–cerebrospinal fluid barrier (mBCSFB). The BBB and mBCSFB comprise highly specialized brain endothelial cells (BECs) that typically restrict pathogen entry. Group B
Streptococcus
(GBS or
Streptococcus agalactiae
) is the leading cause of neonatal meningitis. Until recently, identification of GBS virulence factors has relied on genetic screening approaches. Instead, we here conducted RNA-seq analysis on GBS when interacting with induced pluripotent stem cell-derived BECs (iBECs) to pinpoint virulence-associated genes. Of the 2,068 annotated protein-coding genes of GBS, 430 transcripts displayed significant changes in expression after interacting with BECs. Notably, we found that the majority of differentially expressed GBS transcripts were downregulated (360 genes) during infection of iBECs. Interestingly,
codY
, encoding a pleiotropic transcriptional repressor in low-G + C Gram-positive bacteria, was identified as being highly downregulated. We conducted qPCR to confirm the
codY
downregulation observed via RNA-seq during the GBS–iBEC interaction and obtained
codY
mutants in three different GBS background parental strains. As anticipated from the RNA-seq results, the

∆

codY
strains were more adherent and invasive in two
in vitro
BEC models. Together, this demonstrates the utility of RNA-seq during the BEC interaction to identify GBS virulence modulators.

IMPORTANCE

Group B
Streptococcus
(GBS) meningitis remains the leading cause of neonatal meningitis. Research work has identified surface factors and two-component systems that contribute to GBS disruption of the blood–brain barrier (BBB). These discoveries often relied on genetic screening approaches. Here, we provide transcriptomic data describing how GBS changes its transcriptome when interacting with brain endothelial cells. Additionally, we have phenotypically validated these data by obtaining mutants of a select regulator that is highly down-regulated during infection and testing on our BBB model. This work provides the research field with a validated data set that can provide an insight into potential pathways that GBS requires to interact with the BBB and open the door to new discoveries.
Sequence polymorphisms in the reovirus σ1 attachment protein modulate encapsidation efficiency and replication in mice
Authors: Welsh Olivia L. , Roth Alexa N. , Sutherland Danica M. , Dermody Terence S.
Published: May 2024

Many functions of viral attachment proteins are established, but less is known about the biological importance of viral attachment protein encapsidation efficiency. The mammalian orthoreovirus (reovirus) σ1 attachment protein forms filamentous trimers that incorporate into pentamers of the λ2 capsid protein. Reovirus strains vary in the efficiency of σ1 encapsidation onto progeny virions, which influences viral stability during entry into cells and the efficacy of tumor cell lysis. While the role of σ1 encapsidation has been evaluated in studies using cultured cells, the contribution of attachment protein encapsidation efficiency to viral infection in animals is less clear. Polymorphisms in reovirus σ1 at residues 22 and 249 have been implicated in viral dissemination in mice and susceptibility to proteolysis in the murine intestine, respectively. To determine whether these residues contribute to σ1 encapsidation efficiency, we engineered σ1 mutant viruses with single- and double-residue substitutions at sites 22 and 249. We found that substitutions at these sites alter the encapsidation of σ1 and that reoviruses encapsidating higher amounts of σ1 bind cells more avidly and have a modest replication advantage in a cell-type-specific manner relative to low σ1-encapsidating reoviruses. Furthermore, we found that a high σ1-encapsidating reovirus replicates and disseminates more efficiently in mice relative to a low σ1-encapsidating reovirus. These findings provide evidence of a relationship between viral attachment protein encapsidation efficiency and viral replication in cell culture and animal hosts.

IMPORTANCE

Viral attachment proteins can serve multiple functions during viral replication, including attachment to host cells, cell entry and disassembly, and modulation of host immune responses. The relationship between viral attachment protein encapsidation efficiency and viral replication in cells and animals is poorly understood. We engineered and characterized a panel of reoviruses that differ in the capacity to encapsidate the σ1 attachment protein. We found that strains encapsidating σ1 with higher efficiency bind cells more avidly and replicate and spread more efficiently in mice relative to those encapsidating σ1 with lower efficiency. These results highlight a function for σ1 attachment protein capsid abundance in viral replication in cells and animals, which may inform future use of reovirus as an oncolytic therapeutic.
Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2
in vivo
Authors: Kober Daniel L. , Caballero Van Dyke Marley C. , Eitson Jennifer L. , Boys Ian N. , McDougal Matthew B. , Rosenbaum Daniel M. , Schoggins John W.
Published: May 2024

The rapid evolution of SARS-CoV-2 variants highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses the human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables rapid affinity purification of a dimeric protein by altering the active site to prevent autoproteolytic digestion of a C-terminal His
10
epitope tag. In cultured cells, mutant ACE2 competitively inhibits lentiviral vectors pseudotyped with spikes from multiple SARS-CoV-2 variants and infectious SARS-CoV-2. Moreover, the protein can be nebulized and retains virus-binding properties. We developed a system for the delivery of aerosolized ACE2 to K18-hACE2 mice and demonstrated protection by our modified ACE2 when delivered as a prophylactic agent. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agents
in vivo
and suggest a new tool in the ongoing fight against SARS-CoV-2 and other ACE2-dependent viruses.

IMPORTANCE

The rapid evolution of SARS-CoV-2 variants poses a challenge for immune recognition and antibody therapies. However, the virus is constrained by the requirement that it recognizes a human host receptor protein. A recombinant ACE2 could protect against SARS-CoV-2 infection by functioning as a soluble decoy receptor. We designed a mutant version of ACE2 with impaired catalytic activity to enable the purification of the protein using a single affinity purification step. This protein can be nebulized and retains the ability to bind the relevant domains from SARS-CoV-1 and SARS-CoV-2. Moreover, this protein inhibits viral infection against a panel of coronaviruses in cells. Finally, we developed an aerosolized delivery system for animal studies and show the modified ACE2 offers protection in an animal model of COVID-19. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agents
in vivo
and suggest a new tool in the ongoing fight against SARS-CoV-2.
Draft genome sequence of uropathogenic
Escherichia coli
U13824, a multidrug-resistant (MDR) and extended-spectrum-β-lactamase (ESBL)-producing UPEC strain isolated from an adult woman with urinary tract infection
Authors: Magaña-Lizárraga José Antonio , Gómez-Gil Bruno , Enciso-Ibarra Julisa , Sánchez-Lugo Yesenia , Parra-Unda Jesús Ricardo , Rodríguez-Atondo José Trinidad , Beltrán-Fernández Saúl , Báez-Flores María Elena
Published: May 2024

Urinary tract infections (UTIs) caused by multidrug-resistant and extended-spectrum β-lactamase-producing uropathogenic
Escherichia coli
are a worldwide concern. We report the draft genome of
E. coli
U13824 isolated from a female outpatient with UTI. This genome’s availability strengthens the genomic surveillance of antimicrobial resistance and the spreading of these strains.
Genome sequences of the 15 bluetongue virus vaccine strains incorporated in the South African live-attenuated vaccine
Authors: Mlingo Tendai A. M. , Beeton-Kempen Natasha , Nthangeni M. Bethuel , Theron Jacques , Mokoena Nobalanda B.
Published: May 2024

Bluetongue disease in endemic areas is predominantly controlled through vaccination with live-attenuated vaccines. Sequencing of the original master seed viruses used in the production of Onderstepoort Biological Products vaccine was conducted. Nucleotide identities of 82.97%–100% were obtained for all sequences when compared to South African reference strains.
Metatranscriptomes of California grassland soil microbial communities in response to rewetting
Authors: Chuckran Peter F. , Estera-Molina Katerina , Huntemann Marcel , Foster Brian , Roux Simon , Mukherjee Supratim , Hajek Patrick , Reddy T. B. K. , Daum Chris , Chen I-Min A. , Pennacchio Christa , Eloe-Fadrosh Emiley A. , Dijkstra Paul , Firestone Mary K. , Blazewicz Steven J. , Pett-Ridge Jennifer
Published: May 2024

When very dry soil is rewet, rapid stimulation of microbial activity has important implications for ecosystem biogeochemistry, yet associated changes in microbial transcription are poorly known. Here, we present metatranscriptomes of California annual grassland soil microbial communities, collected over 1 week from soils rewet after a summer drought—providing a time series of short-term transcriptional response during rewetting.
Bioinformatic prediction of proteins relevant to functions of the bacterial OLE ribonucleoprotein complex
Authors: Fernando Chrishan M. , Breaker Ronald R.
Published: May 2024

OLE (ornate, large, extremophilic) RNAs are members of a noncoding RNA class present in many Gram-positive, extremophilic bacteria. The large size, complex structure, and extensive sequence conservation of OLE RNAs are characteristics consistent with the hypothesis that they likely function as ribozymes. The OLE RNA representative from
Halalkalibacterium halodurans
is known to localize to the phospholipid membrane and requires at least three essential protein partners: OapA, OapB, and OapC. However, the precise biochemical functions of this unusual ribonucleoprotein (RNP) complex remain unknown. Genetic disruption of OLE RNA or its partners revealed that the complex is beneficial under diverse stress conditions. To search for additional links between OLE RNA and other cellular components, we used phylogenetic profiling to identify proteins that are either correlated or anticorrelated with the presence of OLE RNA in various bacterial species. This analysis revealed strong correlations between the essential protein-binding partners of OLE RNA and organisms that carry the
ole
gene. Similarly, proteins involved in sporulation are correlated, suggesting a potential role for the OLE RNP complex in spore formation. Intriguingly, the Mg
2+
transporter MpfA is strongly anticorrelated with OLE RNA. Evidence indicates that MpfA is structurally related to OapA and therefore MpfA may serve as a functional replacement for some contributions otherwise performed by the OLE RNP complex in species that lack this device. Indeed, OLE RNAs might represent an ancient RNA class that enabled primitive organisms to sense and respond to major cellular stresses.

IMPORTANCE

OLE (ornate, large, extremophilic) RNAs were first reported nearly 20 years ago, and they represent one of the largest and most intricately folded noncoding RNA classes whose biochemical function remains to be established. Other RNAs with similar size, structural complexity, and extent of sequence conservation have proven to catalyze chemical transformations. Therefore, we speculate that OLE RNAs likewise operate as ribozymes and that they might catalyze a fundamental reaction that has persisted since the RNA World era—a time before the emergence of proteins in evolution. To seek additional clues regarding the function of OLE RNA, we undertook a computational effort to identify potential protein components of the OLE ribonucleoprotein (RNP) complex or other proteins that have functional links to this device. This analysis revealed known protein partners and several additional proteins that might be physically or functionally linked to the OLE RNP complex. Finally, we identified a Mg
2+
transporter protein, MpfA, that strongly anticorrelates with the OLE RNP complex. This latter result suggests that MpfA might perform at least some functions that are like those carried out by the OLE RNP complex.
Population structure and history of
Mycobacterium bovis
European 3 clonal complex reveal transmission across ecological corridors of unrecognized importance in Portugal
Authors: Pereira André C. , Lourenço José , Themudo Gonçalo , Botelho Ana , Cunha Mónica V.
Published: May 2024

Mycobacterium bovis
causes animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a multi-host tuberculosis community from the official hotspot risk area of Portugal over 16 years, generating the largest available data set in the country. Using phylogenetic and ecological modeling, we aimed to reconstruct the history of circulating lineages across the livestock-wildlife interface to inform intervention and the implementation of genomic surveillance within the official eradication plan. We find evidence for the co-circulation of
M. bovis
European 1 (Eu1), Eu2, and Eu3 clonal complexes, with Eu3 providing sufficient temporal signal for further phylogenetic investigation. The Eu3 most recent common ancestor (bovine) was dated in the 1990s, subsequently transitioning to wildlife (red deer and wild boar). Isolate clustering based on sample metadata was used to inform phylogenetic inference, unravelng frequent transmission between two clusters that represent an ecological corridor of previously unrecognized importance in Portugal. The latter was associated with transmission at the livestock-wildlife interface toward locations with higher temperature and precipitation, lower agriculture and road density, and lower host densities. This is the first analysis of
M. bovis
Eu3 complex in Iberia, shedding light on background ecological factors underlying long-term transmission and informing where efforts could be focused within the larger hotspot risk area of Portugal.

IMPORTANCE

Efforts to strengthen surveillance and control of animal tuberculosis (TB) are ongoing worlwide. Here, we developed an eco-phylodynamic framework based on discrete phylogenetic approaches informed by
M. bovis
whole-genome sequence data representing a multi-host transmission system at the livestock-wildlife interface, within a rich ecological landscape in Portugal, to understand transmission processes and translate this knowledge into disease management benefits. We find evidence for the co-circulation of several
M. bovis
clades, with frequent transmission of the Eu3 lineage among cattle and wildlife populations. Most transition events between different ecological settings took place toward host, climate and land use gradients, underscoring animal TB expansion and a potential corridor of unrecognized importance for
M. bovis
maintenance. Results stress that animal TB is an established wildlife disease without ecological barriers, showing that control measures in place are insufficient to prevent long-distance transmission and spillover across multi-host communities, demanding new interventions targeting livestock-wildlife interactions.
U-Pb calcite ages date oblique rifting of the Arctic–North Atlantic gateway
Authors: Haaland L.C. , Slagstad T. , Osmundsen P.T. , Redfield T.
Published: May 2024

Miocene breakup of Svalbard from Greenland formed a deep oceanic gateway that enabled circulation between the Arctic and Atlantic Oceans, significantly changing the global climate. However, the timing of events remains unclear. An excellent opportunity to constrain this timing is found onshore western Svalbard, where the Sarsbukta fault forms the eastern margin of the Eocene–Oligocene Forlandsundet basin. Here, we present new results from U-Pb dating of calcite precipitated in fault-related veins to constrain the timing of Sarsbukta fault deformation and the evolution of the basin. Our oldest calcite age is Permo-Triassic, suggesting long-lived deformation along the fault. A cluster of ages between 41 and 33 Ma overlaps with fossil-based depositional ages from parts of the Forlandsundet basin. These data indicate that onshore transtension partly pre-dated the well-established Chron 13 (magnetic polarity time scale; 35.5–33.7 Ma) reorganization of spreading ridges in the North Atlantic. Our youngest age of 13 Ma indicates that faulting persisted long after the preserved basin fill was deposited. If seafloor spreading marked the end of extension of continental crust, Molloy Ridge spreading during Chron 5 (19.6–9.8 Ma) may have initiated after 13 Ma.
Mortality and adverse events associated with statin use in primary care patients with depression: a real-world, population-based cohort study
Authors: De Giorgi Riccardo , De Crescenzo Franco , Ostinelli Edoardo Giuseppe , Cowen Philip J , Harmer Catherine J , Fazel Seena , Cipriani Andrea
Published: May 2024

Background

New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established.

Objectives

This study aims to assess the real-world mortality and adverse events of statins in depressive disorders.

Methods

Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18–100 years with first-episode depression, registered with English primary care practices over January 1998–August 2020 for 12(+) months, divided into statin users versus non-users.

Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs.

Findings

From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR2–12months0.66–0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR2–6months0.90–0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR12months0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified.

Conclusions

We found no evidence that statin use among people with depression increases mortality or other adverse events.

Clinical implications

Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders.
Study protocol for a scoping review of Lyme disease prediction methodologies
Authors: Szaroz Daniel , Kulkarni Manisha , Robayo González Claudia Ximena , Zinszer Kate
Published: May 2024

Introduction

In the temperate world, Lyme disease (LD) is the most common vector-borne disease affecting humans. In North America, LD surveillance and research have revealed an increasing territorial expansion of hosts, bacteria and vectors that has accompanied an increasing incidence of the disease in humans. To better understand the factors driving disease spread, predictive models can use current and historical data to predict disease occurrence in populations across time and space. Various prediction methods have been used, including approaches to evaluate prediction accuracy and/or performance and a range of predictors in LD risk prediction research. With this scoping review, we aim to document the different modelling approaches including types of forecasting and/or prediction methods, predictors and approaches to evaluating model performance (eg, accuracy).

Methods and analysis

This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines. Electronic databases will be searched via keywords and subject headings (eg, Medical Subject Heading terms). The search will be performed in the following databases: PubMed/MEDLINE, EMBASE, CAB Abstracts, Global Health and SCOPUS. Studies reported in English or French investigating the risk of LD in humans through spatial prediction and temporal forecasting methodologies will be identified and screened. Eligibility criteria will be applied to the list of articles to identify which to retain. Two reviewers will screen titles and abstracts, followed by a full-text screening of the articles’ content. Data will be extracted and charted into a standard form, synthesised and interpreted.

Ethics and dissemination

This scoping review is based on published literature and does not require ethics approval. Findings will be published in peer-reviewed journals and presented at scientific conferences.
Health and well-being needs of Indigenous adolescents: a protocol for a scoping review of qualitative studies
Authors: Sise Andrew , Azzopardi Peter , Brown Alex , Tewhaiti-Smith Jordan , Westhead Seth , Kurji Jaameeta , McDonough Daniel , Reilly Rachel , Bingham Brittany , Brown Ngiare , Cassidy-Matthews Chenoa , Clark Terryann C , Elliott Salenna , Finlay Summer May , Hansen Ketil Lenert , Harwood Matire , Knapp Jonill Margrethe Fjellheim , Kvernmo Siv , Lee Crystal , Watts Ricky-Lee , Nadeau Melanie , Pearson Odette , Reading Jeff , Saewyc Elizabeth , Seljenes Amalie , Stoor Jon Petter A , Aubrey Paula , Crengle Sue
Published: May 2024

Introduction

Improving the health of Indigenous adolescents is central to addressing the health inequities faced by Indigenous peoples. To achieve this, it is critical to understand what is needed from the perspectives of Indigenous adolescents themselves. There have been many qualitative studies that capture the perspectives of Indigenous young people, but synthesis of these has been limited to date.

Methods and analysis

This scoping review seeks to understand the specific health needs and priorities of Indigenous adolescents aged 10–24 years captured via qualitative studies conducted across Australia, Aotearoa New Zealand, Canada, the USA, Greenland and Sami populations (Norway and Sweden). A team of Indigenous and non-Indigenous researchers from these nations will systematically search PubMed (including the MEDLINE, PubMed Central and Bookshelf databases), CINAHL, Embase, Scopus, the Informit Indigenous and Health Collections, Google Scholar, Arctic Health, the Circumpolar Health Bibliographic Database, Native Health Database, iPortal and NZresearch.org, as well as specific websites and clearinghouses within each nation for qualitative studies. We will limit our search to articles published in any language during the preceding 5 years given that needs may have changed significantly over time. Two independent reviewers will identify relevant articles using a two-step process, with disagreements resolved by a third reviewer and the wider research group. Data will then be extracted from included articles using a standardised form, with descriptive synthesis focussing on key needs and priorities. This scoping review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Ethics and dissemination

Ethics approval was not required for this review. Findings will be disseminated via a peer-reviewed journal article and will inform a broader international collaboration for Indigenous adolescent health to develop evidence-based actions and solutions.
Trends in clinical management of lactational mastitis among women attending Australian general practice: a national longitudinal study using MedicineInsight, 2011–2022
Authors: Grzeskowiak Luke E , Kunnel Aline , Crawford Sharinne B , Cullinane Meabh , Amir Lisa Helen
Published: May 2024

Objective

To examine longitudinal trends in clinical management of lactational mastitis in women attending general practice.

Design

Open cohort study.

Setting

Australian general practice using data from MedicineInsight.

Participants

Women aged 18 to 44 years with one or more clinical encounters for lactational mastitis between January 2011 and July 2022.

Primary and secondary outcome measures

The primary outcome measure was the proportion of prescribed oral antibiotics based on the antibiotic type. Secondary outcome measures were the proportion of women prescribed other medications (eg, antifungals, lactation suppressants) or ordered selected clinical investigations including breast ultrasound, blood test, breast milk culture, nipple swab culture or breast aspirate. Outcomes were examined based on the calendar year and individual- or clinical practice-level characteristics.

Results

Among 25 002 women who had one or more clinical encounters related to mastitis, 90.9% were prescribed oral antibiotics. While the proportion of women prescribed an oral antibiotic remained consistent from 2011 to 2022 (91.1% vs 92.5%), there were changes in the proportion receiving prescriptions for di/flucloxacillin (46.1% vs 60.4%) and cefalexin (38.6% vs 26.5%). Fewer than 12% of women were clinically investigated for their mastitis encounter, most commonly a breast ultrasound (7.1%), followed by a selected blood test (3.8%). Requests for breast milk cultures, nipple swab cultures or breast aspirates occurred in less than 1.1% of individuals. Significant increases were evident with respect to ordering of all clinical investigations, with rates at least doubling between 2011 and 2022 (6.6% vs 14.7%). Large variability in clinical management was evident according to both individual- (eg, concessional status) and clinical practice-level characteristics (eg, remoteness).

Conclusions

Australian general practitioners commonly prescribe oral antibiotics to women with mastitis and largely in line with clinical guidelines. Their use of clinical investigations as part of mastitis management has increased over the last decade.
Rhetoric of research: a call for renaming the clinical research partnership
Authors: Foxwell Anessa M , LaRochelle Lillie M , Ulrich Connie M
Published: May 2024

Objective

Research cannot advance without the voluntary participation of human participants.

Summary of arguments

Full participation of research participants is often restrained by the traditional research framework, which relegates them to a predefined participant role and allows them only quasi-scripted opportunities to contribute to research processes and outcomes. Terms commonly used to refer to research participants do not reflect their significant role or send a clear message about their value. The authors propose a shift from ‘patient participant’ to ‘participant partner.’ Recognition of the true partnership between the participant and the research team, from the consent process to the trial’s end, will encourage and enable fuller participation.

Conclusion

Changing the rhetoric of research in the labelling of research participants will require dialogue. ‘Respect for persons’ demands it, and the research process will be better for it.
Barriers to accessing hepatitis B medication: a qualitative study from the USA and Canada
Authors: Jackson Michaela , Ibrahim Yasmin , Freeland Catherine , Jacob Sophie , Zovich Beatrice , Cohen Chari
Published: May 2024

Objectives

To collect and document the numerous barriers that people living with hepatitis B (PLHB) encounter when trying to access their hepatitis B virus (HBV) medications.

Design

Researchers collected qualitative data through 24 online interviews. The semistructured interview questions focused on the impact that HBV has on different aspects of daily life (physical, emotional and social), personal experiences managing their infection, HBV treatment experiences and interactions with healthcare providers.

Setting

All interviews occurred over Zoom.

Participants

The participant cohort consisted of 12 males and 12 females. 63% of all participants represented communities of colour (37% white, 17% black/African/African American and 46% Asian/Asian American). Most of the participants were on antiviral treatment at the time of the study (62%). Participants were PLHB (self-reported), ≥18 years old, living in the USA or Canada and spoke English.

Results

Participants reported several barriers to accessing medicine among PLHB including financial barriers, health insurance and pharmacy preauthorisation process and other intangible barriers like lack of access to reliable patient-friendly information and stigma. The identified barriers to accessing HBV medication impacted patients’ continuity of care.

Conclusions

Access to medicine is essential to improving health outcomes. PLHB experience significant barriers to accessing HBV antivirals at different levels. Patient-related, physician-related and healthcare system barriers were identified as themes contributing to antiviral access challenges. More research is needed to identify strategies to improve access to HBV medications.
Impact of primary care system interventions on healthcare worker satisfaction and intention to stay in the Philippines: a follow-up study
Authors: Tan-Lim Carol Stephanie Chua , Javelosa Mark Anthony U , Sanchez Josephine T , Dans Leonila F , Rey Mia P , Elepano Anton G , De Mesa Regine Ynez H , Dans Antonio L
Published: May 2024

Background

The Philippines has a shortage and uneven distribution of healthcare workers (HCWs). Job satisfaction is an important element to HCW retention and attracting new HCWs into the health system.

Objective

This study measured HCWs’ intent to stay and HCWs’ satisfaction after implementation of multiple interventions intended to strengthen the primary care system, and determine factors significantly associated with HCWs’ intent to stay.

Methodology

This is a serial cross-sectional study in urban, rural and remote primary care sites in the Philippines. All physicians, nurses, midwives, dentists, community health workers and support staff were invited to participate. Baseline HCWs’ intent to stay and satisfaction were obtained using a self-administered questionnaire prior to implementation of interventions. The same survey was again conducted in the years 2021 and 2022, corresponding to 5 and 6 years after initial implementation for the urban site, and 2 and 3 years for the rural and remote sites. We used multiple logistic regression to determine factors associated with intent to stay.

Results

There were 430 survey respondents (89.4% response rate) for year 2021, and 417 survey respondents (97.4% response rate) for year 2022. The urban and rural sites had significant increase in several HCW satisfaction domains, while the remote site had significant decrease in several HCW satisfaction domains. There was no significant difference in the intent to stay in the three sites. Factors that decreased intent to stay included length of employment, job involvement and employment as a nurse, while factors that increased intent to stay included job satisfaction, enjoyment and working in the urban site.

Conclusion

HCW satisfaction improved in the urban site and rural site, while HCW satisfaction declined in the remote site. Intention to stay of primary care HCWs did not significantly change.
Exploring associations of financial well-being with health behaviours and physical and mental health: a cross-sectional study among US adults
Authors: Mercado Carla , Bullard Kai McKeever , Bolduc Michele L F , Banks Desmond , Andrews Courtni , Freggens Zoe R F , Njai Rashid
Published: May 2024

Background

Health disparities exist across socioeconomic status levels, yet empirical evidence between financial well-being (FWB) and health are limited.

Methods

This cross-sectional study combined data from 25 370 adults aged ≥18 years in the 2019 National Health Interview Survey with estimated household FWB scores from the Consumer Financial Protection Bureau’s 2016 National Financial Well-being Survey. FWB associations with health service visits, biometric screenings, smoking status, body mass index and physical and mental conditions were tested using age-adjusted, sex-adjusted and health insurance coverage-adjusted linear regression analysis.

Results

In 2019, the mean FWB for US adults was 56.1 (range 14 (worse) to 95 (best)). With increasing time since the last health service visit or screening, FWB was increasingly lower compared with adults with visits or screenings <1 year (≥10 years or ‘never’, FWB ranged from −1 (blood sugar check) to −6.5 (dental examination/cleaning) points). FWB was lower with declining general health status (excellent (reference), very good (−0.5 points), good (−3.4 points) and fair/poor (−6.6 points)). Adults with physical health conditions had FWB lower than adults without (range −0.4 (high cholesterol) to −4.6 (disability) points). FWB were lower in adults who have ever been diagnosed with anxiety disorder (−1.8 points) or depression (−2 points). Adults managing their anxiety or depression (no/minimal symptoms currently) had greater FWB (anxiety: 3 points and depression: 4.1 points) than those with symptoms.

Conclusion

Given the observed associations between FWB and health-related measures, it is crucial to consider FWB in primary and secondary health prevention efforts, recognising the relationship between economics, health and wellness.
Non-cardiac birth defects and long-term risk of cardiovascular hospitalisation
Authors: Auger Nathalie , Paradis Gilles , Healy-Profitós Jessica , Lewin Antoine , Malik Mariyam , Potter Brian J
Published: May 2024

Background

Patients with heart defects are at risk of developing cardiovascular disease. Our objective was to determine if non-cardiac birth defects are associated with the risk of cardiovascular hospitalisation.

Methods

We conducted a longitudinal cohort study of 1 451 409 parous women in Quebec, Canada. We compared patients with cardiac and non-cardiac birth defects of the urinary, central nervous and other systems against patients without defects between 1989 and 2022. The main outcome was hospitalisation for coronary artery disease, ischaemic stroke and other cardiovascular outcomes during 33 years of follow-up. We computed cardiovascular hospitalisation rates and used Cox proportional hazards regression models to measure the association (HR; 95% CI) between non-cardiac defects and later risk of cardiovascular hospitalisation, adjusted for patient characteristics.

Results

Women with any birth defect had a higher rate of cardiovascular hospitalisation than women without defects (7.0 vs 3.3 per 1000 person-years). Non-cardiac defects overall were associated with 1.61 times the risk of cardiovascular hospitalisation over time, compared with no defect (95% CI 1.56 to 1.66). Isolated urinary (HR 3.93, 95% CI 3.65 to 4.23), central nervous system (HR 3.33, 95% CI 2.94 to 3.76) and digestive defects (HR 2.39, 95% CI 2.16 to 2.65) were associated with the greatest risk of cardiovascular hospitalisation. These anomalies were associated with cardiovascular hospitalisation whether they presented alone or clustered with other defects. Nevertheless, heart defects were associated with the greatest risk of cardiovascular hospitalisation (HR 10.30, 95% CI 9.86 to 10.75).

Conclusion

The findings suggest that both cardiac and non-cardiac birth defects are associated with an increased risk of developing cardiovascular disease among parous women.
RB1: governor of the cell cycle in health and disease—a primer for the practising pathologist
Authors: Cordier Fleur , Creytens David
Published: May 2024

RB1stands as the pioneering discovery in tumour-suppressor genes, marking a pivotal breakthrough in comprehending cancer development. This overview delves into the role ofRB1in both health and disease, exploring its association with the tumourigenesis of various cancers and a distinct subset of soft-tissue neoplasms. Additionally, we discuss the application of immunohistochemistry and fluorescence in situ hybridisation to detectRB1alterations.
Excess mortality among people in homelessness with substance use disorders: a Swedish cohort study
Authors: Gaber Sophie Nadia , Franck Johan , Widing Härje , Hällgren Jonas , Mattsson Elisabet , Westman Jeanette
Published: May 2024

Background

People in homelessness have an increased risk of substance use disorders (SUDs) and poor health outcomes. This cohort study aimed to investigate the association between homelessness and mortality in people with SUDs, adjusting for age, sex, narcotic use, intravenous drug use and inpatient care for SUDs.

Methods

Data from the Swedish National Addiction Care Quality Register in the Stockholm region were used to analyse mortality risk in people with SUDs (n=8397), including 637 in homelessness, 1135 in precarious housing and 6625 in stable housing, at baseline. HRs and CIs were calculated using Cox regression.

Results

Mortality was increased for people in homelessness (HR 2.30; 95% CI 1.70 to 3.12) and precarious housing (HR 1.23; 95% CI 0.86 to 1.75) compared with those in stable housing. The association between homelessness and mortality decreased (HR 1.27; 95% CI 0.91 to 1.78) after adjusting for narcotic use (HR 1.28; 95% CI 1.00 to 1.63), intravenous drug use (HR 1.98; 95% CI 1.52 to 2.58) and inpatient care for SUDs (HR 1.96; 95% CI 1.57 to 2.45). Standardised mortality ratios (SMRs) showed that mortality among people in homelessness with SUDs was 13.6 times higher than the general population (SMR=13.6; 95% CI 10.2 to 17.9), and 3.7 times higher in people in stable housing with SUDs (SMR=3.7; 95% CI 3.2 to 4.1).

Conclusion

Homelessness increased mortality, but the risk decreased after adjusting for narcotic use, intravenous drug use and inpatient care for SUDs. Interventions are needed to reduce excess mortality among people in homelessness with SUDs.
Machine learning for clinical outcome prediction in cerebrovascular and endovascular neurosurgery: systematic review and meta-analysis
Authors: Hoffman Haydn , Sims Jason J , Inoa-Acosta Violiza , Hoit Daniel , Arthur Adam S , Draytsel Dan Y , Kim YeonSoo , Goyal Nitin
Published: May 2024

Background

Machine learning (ML) may be superior to traditional methods for clinical outcome prediction. We sought to systematically review the literature on ML for clinical outcome prediction in cerebrovascular and endovascular neurosurgery.

Methods

A comprehensive literature search was performed, and original studies of patients undergoing cerebrovascular surgeries or endovascular procedures that developed a supervised ML model to predict a postoperative outcome or complication were included.

Results

A total of 60 studies predicting 71 outcomes were included. Most cohorts were derived from single institutions (66.7%). The studies included stroke (32), subarachnoid hemorrhage ((SAH) 16), unruptured aneurysm (7), arteriovenous malformation (4), and cavernous malformation (1). Random forest was the best performing model in 12 studies (20%) followed by XGBoost (13.3%). Among 42 studies in which the ML model was compared with a standard statistical model, ML was superior in 33 (78.6%). Of 10 studies in which the ML model was compared with a non-ML clinical prediction model, ML was superior in nine (90%). External validation was performed in 10 studies (16.7%). In studies predicting functional outcome after mechanical thrombectomy the pooled area under the receiver operator characteristics curve (AUROC) of the test set performances was 0.84 (95% CI 0.79 to 0.88). For studies predicting outcomes after SAH, the pooled AUROCs for functional outcomes and delayed cerebral ischemia were 0.89 (95% CI 0.76 to 0.95) and 0.90 (95% CI 0.66 to 0.98), respectively.

Conclusion

ML performs favorably for clinical outcome prediction in cerebrovascular and endovascular neurosurgery. However, multicenter studies with external validation are needed to ensure the generalizability of these findings.
Aspiration only versus stent retriever only thrombectomy in basilar artery occlusion: a propensity score-matched analysis of the German Stroke Registry
Authors: Wischmann Johannes , Zimmermann Hanna , Keidel Linus , Liebig Thomas , Nolte Christian H , Kellert Lars
Published: May 2024

Background

Endovascular treatment has become the standard care for acute basilar artery occlusion (BAO). Uncertainty persists about the optimal thrombectomy technique.

Objective

To compare aspiration thrombectomy with stent retriever thrombectomy in patients with BAO in a multicenter real-world patient population.

Methods

We analyzed data from the German Stroke Registry-Endovascular Treatment (GSR-ET). Patients with isolated BAO who underwent either aspiration or stent retriever thrombectomy were compared, including propensity score matching (PSM). The primary outcome measure was the modified Rankin Scale shift analysis at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage (sICH), procedure complications, and metrics.

Results

Of 13 082 patients in the GSR-ET, 387 patients (mean age 72.0±13.1 years; 45.0% female) fulfilled the inclusion criteria. The thrombectomy technique was aspiration only in 195 (50.4%) and stent retriever only in 192 (49.6%) patients. Functional outcome did not differ between the groups, either before (common OR (cOR) 0.94; 95% CI 0.64 to 1.38) or after PSM (cOR=1.37; 95% CI 0.90 to 2.09). There was no significant difference in sICH (2.6 vs 5.5%; P=0.231; OR=0.46; 95% CI 0.14 to 1.47), but aspiration thrombectomy demonstrated fewer procedure-related complications (4.6% vs 12.5%; P=0.017), a shorter procedure duration (24 vs 48 min; P<0.001), and higher first pass recanalization rates (75.1% vs 44.8%; P<0.001).

Conclusions

In this study both aspiration and stent retriever thrombectomy showed equal efficacy in terms of functional outcome in patients with BAO. However, procedure complications and metrics might favor aspiration over stent retriever thrombectomy.