bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of contemporary invasive and non-invasive
Streptococcus pneumoniae
isolates reveals new insights into circulating anti-microbial resistance determinants
Authors: Higgs Charlie , Kumar Lamali Sadeesh , Stevens Kerrie , Strachan Janet , Korman Tony , Horan Kristy , Daniel Diane , Russell Madeline , McDevitt Christopher A. , Sherry Norelle L. , Stinear Timothy P. , Howden Benjamin P. , Gorrie Claire L. 
Published: October 2023

ABSTRACT

Streptococcus pneumoniae
is a major human pathogen with a high burden of disease. Non-invasive isolates (those found in non-sterile sites) are thought to be a key source of invasive isolates (those found in sterile sites) and a reservoir of anti-microbial resistance (AMR) determinants. Despite this, pneumococcal surveillance has almost exclusively focused on invasive isolates. We aimed to compare contemporaneous invasive and non-invasive isolate populations to understand how they interact and identify differences in AMR gene distribution. We used a combination of whole-genome sequencing and phenotypic anti-microbial susceptibility testing and a data set of invasive (
n
= 1,288) and non-invasive (
n
= 186) pneumococcal isolates, collected in Victoria, Australia, between 2018 and 2022. The non-invasive population had increased levels of antibiotic resistance to multiple classes of antibiotics including beta-lactam antibiotics penicillin and ceftriaxone. We identified genomic intersections between the invasive and non-invasive populations and no distinct phylogenetic clustering of the two populations. However, this analysis revealed sub-populations overrepresented in each population. The sub-populations that had high levels of AMR were overrepresented in the non-invasive population. We determined that WamR-Pneumo was the most accurate
in silico
tool for predicting resistance to the antibiotics tested. This tool was then used to assess the allelic diversity of the penicillin-binding protein genes, which acquire mutations leading to beta-lactam antibiotic resistance, and found that they were highly conserved (≥80% shared) between the two populations. These findings show the potential of non-invasive isolates to serve as reservoirs of AMR determinants.
Biogeographic distribution and molecular epidemiology of
Clostridioides
(
Clostridium
)
difficile
in Western Australian soils
Authors: Cautivo-Reyes Karla , Knight Daniel R. , Bowie Deborah , Moreira-Grez Benjamin , Whiteley Andrew S. , Riley Thomas V. 
Published: October 2023

ABSTRACT

Clostridioides (Clostridium) difficile
is a leading cause of infectious diarrhea in humans and production animals and can be found in a variety of environmental sources. The prevalence and diversity of multi-locus sequence type clade 5 strains of
C. difficile
in Australian production animals suggest Australia might be the ancestral home of this lineage of One Health importance. To better understand the role of the environment in the colonization of humans and animals in Australia, it is important to investigate these endemic sources. This study describes the prevalence, molecular epidemiology, and biogeographic distribution of
C. difficile
in soils of Western Australia. A total of 321 soil samples from remote geographical locations across the eight health regions of Western Australia were screened for
C. difficile
and isolates characterized by PCR ribotyping and toxin gene profiling.
C. difficile
was isolated from 31.15% of samples, with the highest prevalence in the Perth Metropolitan Health Region (49.25%,
n
= 33/67). Overall, 52 different strains [PCR ribotypes (RTs)] were identified, with 14 being novel, and 38% (38/100) of isolates being toxigenic, the most common of which was RT014/020. Five unique novel isolates showed characteristics similar to
C. difficile
clade 5. This is the first study of
C. difficile
isolated from soils in Australia. The high prevalence and heterogeneity of
C. difficile
strains recovered suggest that soils play a role in the survival and environmental dissemination of this organism, and potentially its transmission among native wildlife and production animals, and in community and hospital settings.

IMPORTANCE

Clostridium difficile
is a pathogen of One Health importance. To better understand the role of the environment in human and animal colonization/infection, it is critical that autochthonous reservoirs/sources of
C. difficile
be investigated. This is the first study of
C. difficile
isolated from soils of Western Australia (WA). Here, the ecology of
C. difficile
in WA is described by examining the geographic distribution, molecular epidemiology, and diversity of
C. difficile
isolated from soils across WA.
Genetic dissection of regulation by a repressing and novel activating corrinoid riboswitch enables engineering of synthetic riboswitches
Authors: Procknow Rebecca R. , Kennedy Kristopher J. , Kluba Maxwell , Rodriguez Lesley J. , Taga Michiko E. 
Published: October 2023

ABSTRACT

The ability to sense and respond to intracellular metabolite levels enables cells to adapt to environmental conditions. Many prokaryotes use riboswitches—structured RNA elements usually located in the 5′ untranslated region of mRNAs—to sense intracellular metabolites and respond by modulating gene expression. The corrinoid riboswitch class, which responds to adenosylcobalamin (coenzyme B
12
) and related metabolites, is among the most widespread in bacteria. The structural elements for corrinoid binding and the requirement for a kissing loop interaction between the aptamer and expression platform domains have been established for several corrinoid riboswitches. However, the conformational changes in the expression platform that modulate gene expression in response to corrinoid binding remain unknown. Here, we employ an
in vivo
GFP reporter system in
Bacillus subtilis
to define alternative secondary structures in the expression platform of a corrinoid riboswitch from
Priestia megaterium
by disrupting and restoring base-pairing interactions. Moreover, we report the discovery and characterization of the first riboswitch known to activate gene expression in response to corrinoids. In both cases, mutually exclusive RNA secondary structures are responsible for promoting or preventing the formation of an intrinsic transcription terminator in response to the corrinoid binding state of the aptamer domain. Knowledge of these regulatory mechanisms allowed us to develop synthetic corrinoid riboswitches that convert repressing riboswitches to riboswitches that robustly induce gene expression in response to corrinoids. Due to their high expression levels, low background, and over 100-fold level of induction, these synthetic riboswitches have potential use as biosensors or genetic tools.

IMPORTANCE

In addition to proteins, microbes can use structured RNAs such as riboswitches for the important task of regulating gene expression. Riboswitches control gene expression by changing their structure in response to binding a small molecule and are widespread among bacteria. Here we determine the mechanism of regulation in a riboswitch that responds to corrinoids—a family of coenzymes related to vitamin B
12
. We report the alternative RNA secondary structures that couple corrinoid sensing with response in a repressing and novel activating corrinoid riboswitch. We then applied this knowledge to flipping the regulatory sign by constructing synthetic riboswitches that activate expression to a higher level than the natural one. In the process, we observed patterns in which sequence, in addition to structure, impacts function in paired RNA regions. The synthetic riboswitches we describe here have potential applications as biosensors.
Experimental analysis of diverse actin-like proteins from various magnetotactic bacteria by functional expression in
Magnetospirillum gryphiswaldense
Authors: Awal Ram Prasad , Müller Frank D. , Pfeiffer Daniel , Monteil Caroline L. , Perrière Guy , Lefèvre Christopher T. , Schüler Dirk 
Published: October 2023

ABSTRACT

Magnetotactic bacteria (MTB) produce magnetosomes, which are sensory organelles consisting of nanocrystals of a magnetic iron mineral enclosed by membranes. In the well-characterized
Magnetospirillum
species of the
Alphaproteobacteria
, magnetosomes align and form highly ordered chains along filaments that consist of the bacterial actin homolog MamK. The MamK protein is part of a multi-component “magnetoskeleton” that controls the concatenation, positioning, and partitioning of the magnetosome chains (MCs) which serve as cellular compass for efficient navigation in the Earth’s magnetic field. MamK is highly conserved in all MTB; however, it is unknown whether its magnetoskeletal function is preserved, especially in those MTB which exhibit distinct and more complex architectures of MCs and often contain additional putative magnetoskeletal constituents such as the actin-like protein Mad28 with as yet-unknown functions. Here, we studied the ability of magnetosome-associated actins from a wide range of diverse MTB to rescue well-characterized magnetoskeleton mutants of the model
Magnetospirillum gryphiswaldense
. We found that MamK orthologs from
Alpha-
,
Delta-
,
Candidatus Etaproteo-
, and
Nitrospirota
-MTB as well as a resurrected MamK LUCA version restored MC assembly to varying degrees and exhibited filamentous localization in
M. gryphiswaldense
and
E. coli
. We also identified a novel magnetosome-related protein from the magnetotactic alphaproteobacterium
Magnetovibrio blakemorei
that substitutes the function of the well-characterized MamJ protein as a molecular adaptor tethering magnetosomes to MamK filaments. Moreover, we demonstrate that Mad28 orthologs from
Thermodesulfobacteriota
and
Nitrospirota
are actin-like proteins that can functionally complement
mamK
mutants of
M. gryphiswaldense
and which form filamentous structures
in vivo and in vitro
.

IMPORTANCE
To efficiently navigate within the geomagnetic field, magnetotactic bacteria (MTB) align their magnetosome organelles into chains, which are organized by the actin-like MamK protein. Although MamK is the most highly conserved magnetosome protein common to all MTB, its analysis has been confined to a small subgroup owing to the inaccessibility of most MTB. Our study takes advantage of a genetically tractable host where expression of diverse MamK orthologs together with a resurrected MamK LUCA and uncharacterized actin-like Mad28 proteins from deep-branching MTB resulted in gradual restoration of magnetosome chains in various mutants. Our results further indicate the existence of species-specific MamK interactors and shed light on the evolutionary relationships of one of the key proteins associated with bacterial magnetotaxis.
Ultrasound guided lavage with corticosteroid injection versus sham lavage with and without corticosteroid injection for calcific tendinopathy of shoulder: randomised double blinded multi-arm study
Authors: Moosmayer Stefan , Ekeberg Ole Marius , Hallgren Hanna Björnsson , Heier Ingar , Kvalheim Synnøve , Juel Niels Gunnar , Blomquist Jesper , Pripp Are Hugo , Brox Jens Ivar 
Published: October 2023

Abstract

Objective
To compare treatment effects between ultrasound guided lavage with corticosteroid injection and sham lavage with and without corticosteroid injection in patients with calcific tendinopathy of the shoulder.

Design
Pragmatic, three arm, parallel group, double blinded, sham controlled, randomised, superiority trial with repeated measurements over 24 months.

Setting
Six hospitals in Norway and Sweden.

Participants
220 adults with calcific tendinopathy of the shoulder, persistent for at least three months.

Interventions
Ultrasound guided deposit lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (lavage+steroid); sham lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (sham lavage+steroid); or sham lavage plus subacromial injection of 10 mL 1% lidocaine hydrochloride (sham). All patients received a physiotherapeutic treatment regimen consisting of four home exercises.

Main outcome measures
The primary outcome was the result on the 48 point scale (0=worst; 48=best) of the Oxford Shoulder Score (OSS) at four month follow-up. Secondary outcomes included measurements on the short form of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) and of pain intensity up to 24 months. The influence of the size of the deposit at baseline and of the persistence or disappearance of the deposit was investigated.

Results
Data from 218 (99%) participants were included in the primary analysis. Differences between groups on the OSS at four months were not significant: lavage+steroid versus sham 0.2 (95% confidence interval −2.3 to 2.8; P=1.0); sham lavage+steroid versus sham 2.0 (−0.5 to 4.6; P=0.35); lavage+steroid versus sham lavage+steroid −1.8 (−4.3 to 0.7; P=0.47). After four months, 143 patients with insufficient treatment effect received supplementary treatment. At 24 months, none of the study procedures was superior to sham. No serious adverse events were reported.

Conclusions
This study found no benefit for ultrasound guided lavage with a corticosteroid injection or for sham lavage with a corticosteroid injection compared with sham treatment in patients with calcific rotator cuff tendinopathy of the shoulder.

Trial registration

NCT02419040EudraCT 2015-002343-34; Ethical committee Norway 2015-002343-34; Ethical committee Sweden 2015/79-31; Clinicaltrials.gov
NCT02419040
.
Evaluating the impact on health outcomes of an event that resulted in a delay in contact tracing of COVID-19 cases in England, September 2020: an observational study
Authors: Findlater Lucy , Pierotti Livia , Turner Charlie , Wensley Adrian , Chen Cong , Seaman Shaun , Samartsidis Pantelis , Charlett Andre , Anderson Charlotte , Hughes Gareth , Hickman Matthew , Edeghere Obaghe , Oliver Isabel 
Published: October 2023

ObjectiveIn September 2020, 15 861 SARS-CoV-2 case records failed to upload from the Second Generation Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, delaying the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on population health outcomes: transmission events, hospitalisations and mortality. Previously, a modelling study suggested a substantial impact.DesignObservational study.SettingEngland.PopulationIndividuals testing positive for SARS-CoV-2 and their reported contacts.Main outcome measuresSecondary attack rates (SARs), hospitalisations and deaths among primary and secondary contacts were calculated, compared with all other concurrent, unaffected cases. Affected SGSS records were matched to CTAS records. Successive contacts and cases were identified and matched to hospital episode and mortality outcomes.ResultsInitiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared with the control group (3 days). This was associated with lower completion of contact tracing: 80% (95% CI: 79% to 81%) in delay group and 83% (95% CI: 83% to 84%) in control group. There was some evidence to suggest increased transmission to non-household contacts among those affected by the delay. The SAR for non-household contacts was higher among secondary contacts in the delay group than the control group (delay group: 7.9%, 95% CI: 6.5% to 9.2%; control group: 5.9%, 95% CI: 5.3% to 6.6%). There did not appear to be a significant difference between the delay and control groups in the odds of hospitalisation (crude OR: 1.1 (95% CI: 0.9 to 1.2)) or death (crude OR: 0.7 (95% CI: 0.1 to 4.0)) among secondary contacts.ConclusionsOur analysis suggests that the delay in contact tracing had a limited impact on population health outcomes; however, contact tracing was not completed for all individuals, so some transmission events might not be captured.
Cross-sectional analyses of online appointment booking and repeat prescription ordering user characteristics in general practices of England in the years 2018–2020
Authors: Alturkistani Abrar , Greenfield Geva , Beaney Thomas , Norton John , Costelloe Ceire E 
Published: October 2023

ObjectivesTo explore the characteristics of the General Practice Patient Survey (GPPS) respondents using the different functionalities of the online services in the context of England’s National Health Service General Practices. We hypothesised that respondents who are older, with lower socioeconomic status and non-white ethnicity would be less likely to use online services, while long-term conditions might increase their usage.DesignCross-sectional study using respondent-level data from the GPPS in England of the years 2018, 2019 and 2020. We assessed the association between online services use and respondent characteristics using two-level mixed-effects logistic regression.ParticipantsSurvey respondents of the GPPS 2018–2020.Primary outcome measuresOnline appointment booking and online repeat prescription ordering.Results1 807 049 survey respondents were included in this study. 15% (n=263 938) used online appointment booking in the previous 12 months, and 19% (n=339 449) had ordered a repeat prescription in the previous 12 months. Respondents with a long-term condition, on regular multiple medications, who have deafness or hearing loss and who are from the lowest deprivation quintile were more likely to have used online services. Male respondents (compared with females) and respondents with black and other ethnicity compared with white ethnicity were less likely to use online services. Respondents over 85 years old were less likely to use online appointment booking and online repeat prescription ordering compared with the younger age groups.ConclusionsSpecific groups of respondents were more likely to use online services such as patients with long-term conditions or those with deafness or hearing loss. While online services could provide efficiency to patients and practices it is essential that alternatives continue to be provided to those that cannot use or choose not to use online services. Understanding the different patients’ needs could inform solutions to increase the uptake and use of the services.
Factors influencing choice of b/ts DMARDs in managing inflammatory arthritis from a patient perspective: a systematic review of global evidence and a patient-based survey from Hong Kong
Authors: Li Yihua , Lau Lauren K W , Peng Kuan , Zhang Dexing , Dong Dong , Wong Ian C K , Li Xue 
Published: October 2023

ObjectivesTo investigate factors concerning patients regarding biological/target synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) in treating inflammatory arthritis (IA).DesignThis study consists of a systematic review and a cross-sectional survey in Hong Kong. A systematic review of literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted on PubMed, Web of Science, Cochrane and Embase between 1 January 2000 and 1 January 2022. Content analysis was conducted to summarise factors grouped by four themes—social aspects (SA), clinical aspects (CA), medicine characteristics (MC) and financial aspects (FA) in the decision-making process. One cross-sectional survey among Hong Kong patients with IA was conducted to add to global evidence.SettingA systematic review of global evidence and a patient-based survey in Hong Kong to complement scarce evidence in Asia regions.ResultsThe systematic review resulted in 34 studies. The four themes were presented in descending order consistently but varied with frequency throughout decision-making processes. During decision-making involving medication initiation, preference and discontinuation, MC (reported frequency: 83%, 86%, 78%), SA (56%, 43%, 78%) and FA (39%, 33%, 56%) were the three most frequently reported factors, whereas CA was less studied. Local survey also revealed that MC factors such as treatment efficacy and the probability of severe adverse events, and SA factors such as the availability of government or charity subsidy, influenced patients’ initiation and preference for b/ts DMARDs. Meanwhile, self-estimated improvement in disease conditions (SA), drug side effects (MC) and drug costs (FA) were associated with treatment discontinuation.ConclusionsGlobal and local evidence consistently indicate that MC and SA are important considerations in patients’ decisions regarding novel DMARDs. Health policies that reduce patients’ financial burden and enhances healthcare professionals’ engagement in decision-making and treatment delivery should be in place with an efficient healthcare system for managing IA optimistically.
Province-level distribution and drivers of infant mortality in mainland China: a Geodetector-based analysis of data from 2020
Authors: Zhang Xiao , Tang Yuwen , Zhang Beibei , Zhang Yongjing , Dai Jifeng , Zhang Junhui 
Published: October 2023

ObjectiveThe present study investigated the province-level distribution and drivers of infant mortality rate (IMR) in mainland China.DesignEcological analysis based on publicly available data for all 31 provinces in mainland China.Data sourcesData on province-level IMRs in 2020 were obtained from the official websites of the healthcare commissions within each province and from the China Health Statistics Yearbook 2021. Data on potential IMR drivers were retrieved from the China Statistical Yearbook 2021.Data analysisGeoDa V.1.12.1 and ArcMap V.10.2 software were used to examine province-level distribution of IMR. Global and local spatial autocorrelations were performed, and Getis-ord G* hotspots and coldspots were identified. Geodetector was used to analyse the individual and joint influence of drivers on IMR.ResultsIMRs in 2020 varied from 1.91 to 7.60 per 1000 live births across provinces. The following statistically significant drivers with q values >0.5 were identified: health literacy of the population (0.6673), male illiteracy rate (0.6433), proportion of the population older than >65 years (0.6369), per capita government health expenditure (0.6216), forest coverage rate (0.5820), per capita disposable income (0.5785), per capita number of hospitals (0.5592), per capita gross regional product (0.5410) and sulfur dioxide concentration in the atmosphere (0.5158). The following three interactions among these drivers emerged as strongest influences on province-level IMR: proportion of population >65 years ∩ per capita gross regional product (q=0.9653), forest coverage rate ∩ per capita gross regional product (0.9610) and per capita government health expenditure ∩ sulfur dioxide (0.9295).ConclusionIMR in mainland China varies substantially across the country, being generally high-west and low-east. Several factors, on their own and interacting together, contribute to IMR. Policies and programmes to reduce IMR should be formulated according to local conditions and should focus on western provinces of the country.