bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing the flavodoxin landscape in
Clostridioides difficile
Authors: Troitzsch Daniel , Knop Robert , Dittmann Silvia , Bartel Jürgen , Zühlke Daniela , Möller Timon Alexander , Trän Linda , Echelmeyer Thaddäus , Sievers Susanne
Published: February 2024

Clostridioides difficile
infections have become a major challenge in medical facilities. The bacterium is capable of spore formation allowing the survival of antibiotic treatment. Therefore, research on the physiology of
C. difficile
is important for the development of alternative treatment strategies. In this study, we investigated eight putative flavodoxins of
C. difficile
630. Flavodoxins are small electron transfer proteins of specifically low potential. The unusually high number of flavodoxins in
C. difficile
suggests that they are expressed under different conditions. We determined high transcription levels for several flavodoxins during the exponential growth phase, especially for
floX
. Since flavodoxins are capable of replacing ferredoxins under iron deficiency conditions in other bacteria, we also examined their expression in
C. difficile
under low iron and no iron levels. In particular, the amount of
fldX
increased with decreasing iron concentration and thus could possibly replace ferredoxins. Moreover, we demonstrated that
fldX
is increasingly expressed under different oxidative stress conditions and thus may play an important role in the oxidative stress response. While increased
fldX
expression was detectable at both RNA and protein level,
CD2825
showed increased expression only at mRNA level under H
2
O
2
stress with sufficient iron availability and may indicate hydroxyl radical-dependent transcription. Although the exact function of the individual flavodoxins in
C. difficile
needs to be further investigated, the present study shows that flavodoxins could play an important role in several physiological processes and under infection-relevant conditions.

IMPORTANCE

The gram-positive, anaerobic, and spore-forming bacterium
Clostridioides difficile
has become a vast problem in human health care facilities. The antibiotic-associated infection with this intestinal pathogen causes serious and recurrent inflammation of the intestinal epithelium, in many cases with a severe course. To come up with novel targeted therapies against
C. difficile
infections, a more detailed knowledge on the pathogen’s physiology is mandatory. Eight putative flavodoxins, an extraordinarily high copy number of this type of small electron transfer proteins, are annotated for
C. difficile
. Flavodoxins are known to be essential electron carriers in other bacteria, for instance, during infection-relevant conditions such as iron limitation and oxidative stress. This work is a first and comprehensive overview on characteristics and expression profiles of the putative flavodoxins in the pathogen
C. difficile
.
In situ
community transcriptomics illuminates CO
2
-fixation potentials and supporting roles of phagotrophy and proton pump in plankton in a subtropical marginal sea
Authors: Li Hongfei , Chen Jianwei , Yu Liying , Fan Guangyi , Li Tangcheng , Li Ling , Yuan Huatao , Wang Jingtian , Wang Cong , Li Denghui , Lin Senjie
Published: February 2024

Lineage-wise physiological activities of plankton communities in the ocean are important but challenging to characterize. Here, we conducted whole-assemblage metatranscriptomic profiling at continental shelf and slope sites in the South China Sea to investigate carbon fixation potential in different lineages.
RuBisCO
expression, the proxy of Calvin carbon fixation (CCF) potential, was mainly contributed by Bacillariophyta, Chlorophyta, Cyanobacteria, and Haptophyta, which was differentially affected by environmental factors among lineages. CCF potential exhibited positive or negative correlations with phagotrophy gene expression, suggesting phagotrophy possibly enhances or complements CCF. Our data also reveal significant non-Calvin carbon fixation (NCF) potential, as indicated by the active expression of genes in all five currently recognized NCF pathways, mainly contributed by Flavobacteriales, Alteromonadales, and Oceanospirillales. Furthermore, in Flavobacteriales, Alteromonadales, Pelagibacterales, and Rhodobacterales, NCF potential was positively correlated with proton-pump rhodopsin (PPR) expression, suggesting that NCF might be energetically supported by PPR. The novel insights into the lineage-differential potential of carbon fixation, widespread mixotrophy, and PPR as an energy source for NCF lay a methodological and informational foundation for further research to understand carbon fixation and the trophic landscape in the ocean.

IMPORTANCE

Marine plankton plays an important role in global carbon cycling and climate regulation. Phytoplankton and cyanobacteria fix CO
2
to produce organic compounds using solar energy and mainly by the Calvin cycle, whereas autotrophic bacteria and archaea may fix CO
2
by non-Calvin cycle carbon fixation pathways. How active individual lineages are in carbon fixation and mixotrophy, and what energy source bacteria may employ in non-Calvin carbon fixation, in a natural plankton assemblage are poorly understood and underexplored. Using metatranscriptomics, we studied carbon fixation in marine plankton with lineage resolution in tropical marginal shelf and slope areas. Based on the sequencing results, we characterized the carbon fixation potential of different lineages and assessed Calvin- and non-Calvin- carbon fixation activities and energy sources. Data revealed a high number of unigenes (4.4 million), lineage-dependent differential potentials of Calvin carbon fixation and responses to environmental conditions, major contributors of non-Calvin carbon fixation, and their potential energy source.
Campylobacter jejuni
extracellular vesicles harboring cytolethal distending toxin bind host cell glycans and induce cell cycle arrest in host cells
Authors: Le Lena Hoang My , Elgamoudi Bassam , Colon Nina , Cramond Angus , Poly Frederic , Ying Le , Korolik Victoria , Ferrero Richard L.
Published: February 2024

Cytolethal distending toxins (CDTs) are released by Gram-negative pathogens into the extracellular medium as free toxin or associated with extracellular vesicles (EVs), commonly known as outer membrane vesicles (OMVs). CDT production by the gastrointestinal pathogen
Campylobacter jejuni
has been implicated in colorectal tumorigenesis. Despite CDT being a major virulence factor for
C. jejuni
, little is known about the EV-associated form of this toxin. To address this point, C.
jejuni
mutants lacking each of the three CDT subunits (A, B, and C) were generated.
C. jejuni cdtA, cdtB,
and
cdtC
bacteria released EVs in similar numbers and sizes to wild-type bacteria, ranging from 5 to 530 nm (mean ± SEM = 118 ±6.9 nm). As the CdtAC subunits mediate toxin binding to host cells, we performed “surface shearing” experiments, in which EVs were treated with proteinase K and incubated with host cells. These experiments indicated that CDT subunits are internal to EVs and that surface proteins are probably not involved in EV-host cell interactions. Furthermore, glycan array studies demonstrated that EVs bind complex host cell glycans and share receptor binding specificities with
C. jejuni
bacteria for fucosyl GM1 ganglioside, P1 blood group antigen, sialyl, and sulfated Lewis
x
. Finally, we show that EVs from
C. jejuni
WT but not mutant bacteria induce cell cycle arrest in epithelial cells. In conclusion, we propose that EVs are an important mechanism for CDT release by
C. jejuni
and are likely to play a significant role in toxin delivery to host cells.

IMPORTANCE

Campylobacter jejuni
is the leading cause of foodborne gastroenteritis in humans worldwide and a significant cause of childhood mortality due to diarrheal disease in developing countries. A major factor by which
C. jejuni
causes disease is a toxin, called cytolethal distending toxin (CDT). The biology of this toxin, however, is poorly understood. In this study, we report that
C. jejuni
CDT is protected within membrane blebs, known as extracellular vesicles (EVs), released by the bacterium. We showed that proteins on the surfaces of EVs are not required for EV uptake by host cells. Furthermore, we identified several sugar receptors that may be required for EV binding to host cells. By studying the EV-associated form of
C. jejuni
CDT, we will gain a greater understanding of how
C. jejuni
intoxicates host cells and how EV-associated CDT may be used in various therapeutic applications, including as anti-tumor therapies.
We need to talk about ‘bad’ resilience
Authors: Saulnier Dell D , Topp Stephanie M
Published: February 2024

In this analysis, we argue against seeing health system resilience as an inherently positive concept. The rise in the popularity of health system resilience has led to its increasingly normative framing. We question this widely accepted perspective by examining the underlying assumptions associated with this normative framing of ‘good’ resilience. Our focus is on the risks of accepting the assumption, which can lead us to ignore the social nature of health systems and overlook the consequences of change if resilience is seen as a positive, achievable objective. Finally, we suggest that seeing resilience as a normative concept can be detrimental to health system policy and research, and encourage a critical rethinking of these assumptions so that we can maintain resilience’s usefulness for health systems.
Urinary 8-hydroxy-2′-deoxyguanosine levels and preterm births: a prospective cohort study from the Japan Environment and Children’s Study
Authors: Murata Tsuyoshi , Kyozuka Hyo , Fukuda Toma , Imaizumi Karin , Isogami Hirotaka , Kanno Aya , Yasuda Shun , Yamaguchi Akiko , Sato Akiko , Ogata Yuka , Shinoki Kosei , Hosoya Mitsuaki , Yasumura Seiji , Hashimoto Koichi , Nishigori Hidekazu , Fujimori Keiya
Published: February 2024

Objectives

To evaluate the association between urinary 8-hydroxy-2′-deoxyguanosine (U8-OHdG) level—a marker of oxidative stress—and the incidence of preterm births (PTBs).

Design

Prospective cohort study.

Setting

The Japan Environment and Children’s Study (JECS).

Participants

Data from 92 715 women with singleton pregnancies at and after 22 weeks of gestation who were enrolled in the JECS, a nationwide birth cohort study, between 2011 and 2014 were analysed. U8-OHdG levels were assessed once in the second/third trimester using liquid chromatography–tandem mass spectrometry. Participants were categorised into the following three or five groups: low (<1.95 ng/mg urinary creatinine (Cre)), moderate (1.95–2.94 ng/mg Cre) and high (≥2.95 ng/mg Cre) U8-OHdG groups, or groups with <1.87, 1.87–2.20, 2.21–2.57, 2.58–3.11 and ≥3.12 ng/mg Cre. For stratification, participants with representative causes for artificial PTB were excluded.

Primary and secondary outcome measures

Adjusted OR (aOR) for PTB before 37 and 34 weeks of gestation were calculated using a multivariable logistic regression model while adjusting for confounding factors; the moderate or lowest U8-OHdG group was used as the reference, respectively.

Results

The aORs for PTB before 37 weeks of gestation in the high U8-OHdG group were 1.13 (95% CI 1.05 to 1.22) and 1.13 (95% CI 1.04 to 1.23) after stratification. The aOR for PTB before 37 weeks in the fourth group was 0.90 (95% CI 0.81 to 0.99). After stratification, the aORs for PTB before 37 and 34 weeks in the fifth group were 1.15 (95% CI 1.03 to 1.29) and 1.46 (95% CI 1.08 to 1.97), respectively.

Conclusions

High U8-OHdG levels were associated with increased PTB incidence, especially in participants without representative causes for artificial PTB. Our results can help identify the mechanisms leading to PTB, considering the variable aetiologies of this condition; further validation is needed to clarify clinical impacts.
Protocol for the Gut Bugs in Autism Trial: a double-blind randomised placebo-controlled trial of faecal microbiome transfer for the treatment of gastrointestinal symptoms in autistic adolescents and adults
Authors: Tweedie-Cullen Ry Y , Leong Karen , Wilson Brooke C , Derraik José G B , Albert Benjamin B , Monk Ruth , Vatanen Tommi , Creagh Christine , Depczynski Marysia , Edwards Taygen , Beck Kathryn , Thabrew Hiran , O'Sullivan Justin M , Cutfield Wayne S
Published: February 2024

Introduction

Autism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and can adversely affect their quality of life. This study aims to evaluate the efficacy of oral encapsulated faecal microbiome transfer (FMT) in improving gastrointestinal symptoms and well-being among autistic adolescents and adults.

Methods and analysis

This double-blind, randomised, placebo-controlled trial will recruit 100 autistic adolescents and adults aged 16–45 years, who have mild to severe gastrointestinal symptoms (Gastrointestinal Symptoms Rating Scale (GSRS) score ≥2.0). We will also recruit eight healthy donors aged 18–32 years, who will undergo extensive clinical screening. Recipients will be randomised 1:1 to receive FMT or placebo, stratified by biological sex. Capsules will be administered over two consecutive days following an overnight bowel cleanse with follow-up assessments at 6, 12 and 26 weeks post-treatment. The primary outcome is GSRS score at 6 weeks. Other assessments include anthropometry, body composition, hair cortisol concentration, gut microbiome profile, urine/plasma gut-derived metabolites, plasma markers of gut inflammation/permeability and questionnaires on general well-being, sleep quality, physical activity, food diversity and treatment tolerability. Adverse events will be recorded and reviewed by an independent data monitoring committee.

Ethics and dissemination

Ethics approval for the study was granted by the Central Health and Disability Ethics Committee on 24 August 2021 (reference number: 21/CEN/211). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.

Trial registration number

ACTRN12622000015741.
Oral Probiotic Supplementation in Pregnancy to Reduce Group B Streptococcus Colonisation (OPSiP trial): study protocol for a double-blind parallel group randomised placebo trial
Authors: Hayes Kelly , Janssen Patricia , Payne Beth A , Jevitt Cecilia , Johnston Will , Johnson Patricia , Butler Michelle
Published: February 2024

Introduction

Group B streptococcus(GBS), orStreptococcus agalactiae, remains a leading cause of neonatal morbidity and mortality. Canadian guidelines advise universal maternal screening for GBS colonisation in pregnancy in conjunction with selective antibiotic therapy. This results in over 1000 pregnant individuals receiving antibiotic therapy to prevent one case of early-onset neonatal GBS disease, and over 20 000 pregnant individuals receiving antibiotic therapy to prevent one neonatal death. Given the growing concern regarding the risk of negative sequela from antibiotic exposure, it is vital that alternative approaches to reduce maternal GBS colonisation are explored.

Preliminary studies suggest some probiotic strains could confer protection in pregnancy against GBS colonisation.

Methods and analysis

This double-blind parallel group randomised trial aims to recruit 450 pregnant participants in Vancouver, BC, Canada and will compare GBS colonisation rates in those who have received a daily oral dose of three strains of probiotics with those who have received a placebo. The primary outcome will be GBS colonisation status, measured using a vaginal/rectal swab obtained between 35 weeks’ gestation and delivery. Secondary outcomes will include maternal antibiotic exposure and urogenital infections. Analysis will be on an intention-to-treat basis.

Patient or public involvement

There was no patient or public involvement in the design of the study protocol.

Ethics and dissemination

This study protocol received ethics approval from the University of British Columbia’s Clinical Research Ethics Board, Dublin City University and Health Canada. Findings will be presented at research rounds, conferences and in peer-reviewed publications.

Trial registration number

NCT03407157.
Beating the empty pelvis syndrome: the PelvEx Collaborative core outcome set study protocol
Authors:   PelvEx Collaborative
Published: February 2024

Introduction

The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.

Methods and analysis

A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.

Ethics and dissemination

The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.

Trial registration number

NCT05683795.
Development and psychometric properties evaluation of nurses’ innovative behaviours inventory in Iran: protocol for a sequential exploratory mixed-method study
Authors: Shahidi Delshad Elham , Soleimani Mohsen , Zareiyan Armin , Ghods Ali Asghar
Published: February 2024

Introduction

Nurses’ innovative behaviours play a crucial role in addressing the challenges including adapting to emerging technologies, resource limitations and social realities such as population ageing that are intricately tied to today’s healthcare landscape. Innovative behaviours improve healthcare quality, patient safety and satisfaction. Organisational factors and individual attributes influence nurses’ inclination to innovate. With the rise of artificial intelligence and novel technology, healthcare institutions are actively engaged in the pursuit of identifying nurses who demonstrate innovative qualities. Developing a comprehensive protocol to elucidate the various dimensions of nurses’ innovative behaviours and constructing a valid measuring instrument, rooted in this protocol represents a significant step in operationalising this concept.

Methods and analysis

The study encompasses two phases: a qualitative study combined with a literature review, followed by the design and psychometric evaluation of the instrument. To ensure diversity, a maximum variation purposive sampling method will be used during the qualitative phase to select clinical nurses. In-depth semistructured interviews will be conducted and analysed using conventional content analysis. Additionally, a comprehensive literature review will supplement any missing features not captured in the qualitative phase, ensuring their inclusion in the primary tool. The subsequent quantitative phase will focus on evaluating the questionnaire’s psychometric properties, including face, content and construct validity through exploratory factor analyses (including at least 300 samples) and confirmatory factor analyses (including at least 200 samples). Internal consistency (Cronbach’s alpha), reliability (test–retest), responsiveness, interpretability and scoring will also be assessed.

Ethics and dissemination

This study originates from a doctoral dissertation in nursing. Permission and ethical approval from Semnan University of Medical Sciences has been obtained with reference code IR.SEMUMS.1401.226. The study’s findings will ultimately be submitted as a research paper to a peer-reviewed journal.
Study to evaluate the readability and visual appearance of online resources for blunt chest trauma: an evaluation of online resources using mixed methods
Authors: Hutchings Hayley Anne , Cochrane Max , Battle Ceri
Published: February 2024

Objectives

Blunt chest trauma (BCT) is characterised by forceful and non-penetrative impact to the chest region. Increased access to the internet has led to online healthcare resources becoming used by the public to educate themselves about medical conditions. This study aimed to determine whether online resources for BCT are at an appropriate readability level and visual appearance for the public.

Design

We undertook a (1) a narrative overview assessment of the website; (2) a visual assessment of the identified website material content using an adapted framework of predetermined key criteria based on the Centers for Medicare and Medicaid Services toolkit and (3) a readability assessment using five readability scores and the Flesch reading ease score using Readable software.

Data sources

Using a range of key search terms, we searched Google, Bing and Yahoo websites on 9 October 2023 for online resources about BCT.

Results

We identified and assessed 85 websites. The median visual assessment score for the identified websites was 22, with a range of −14 to 37. The median readability score generated was 9 (14–15 years), with a range of 4.9–15.8. There was a significant association between the visual assessment and readability scores with a tendency for websites with lower readability scores having higher scores for the visual assessment (Spearman’s r=−0.485; p<0.01). The median score for Flesch reading ease was 63.9 (plain English) with a range of 21.1–85.3.

Conclusions

Although the readability levels and visual appearance were acceptable for the public for many websites, many of the resources had much higher readability scores than the recommended level (8–10) and visually were poor.

Better use of images would improve the appearance of websites further. Less medical terminology and shorter word and sentence length would also allow the public to comprehend the contained information more easily.
Implementing a contextually appropriate foot-ankle exercise programme in primary care for the prevention of modifiable risk factors for ulcers in people with diabetes: protocol for a hybrid type 2 study
Authors: Rodrigues Carla B , Soares Paula N C , Schmitt Ana Carolina B , Sacco Isabel C N
Published: February 2024

Introduction

Diabetes is a highly prevalent disease that negatively impacts people’s health and quality of life. It can result in diabetic peripheral neuropathy (DPN) and foot complications, which in turn lead to ulcers and amputations. The international guidelines on diabetic foot included specific foot-ankle exercises as preventive strategy capable of modifying the risk factors for ulcers. Our aim is to test the effectiveness and to implement a contextually appropriate preventive intervention—a foot-ankle exercises programme alongside educational strategies—in a primary care setting to improve range of motion (ROM), strength, functionality of foot-ankle, and quality of life in people with diabetes.

Methods and analysis

This is a hybrid type 2 implementation-effectiveness study organised in four phases, being undertaken in Limeira, São Paulo. Phase 1, preimplementation, aims to gather information about the contextual characteristics, barriers, and facilitators and to form the implementation team. In phase 2, the implementation team will structure the foot-ankle programme, adapting it to the context of primary healthcare, and develop the training for health professionals. In phase 3, effectiveness of the 12 week group-based intervention will be tested by a cluster randomised controlled trial. Primary care units (18 clusters) will be randomly allocated to a control or intervention group, with a total sample of 356 people. Primary outcomes will be DPN symptoms and ankle and first metatarsal phalangeal joint ROM. Reach, adoption, and implementation will be evaluated by Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. In phase 4, maintenance and expansion of the programme in the municipality will be assessed.

Ethics and dissemination

This protocol and the informed consent to be signed by the participants were approved by the Ethics Committee of the School of Medicine of the University of São Paulo (CAAE:63457822.0.0000.0068, 29 November 2022). The project will generate and share data in a public repository. Results will be disseminated through peer-reviewed journals, conference proceedings, and electronic communications for health professionals.

Trial registration number

NCT05639478.
Missed opportunities in hospital quality measurement during the COVID-19 pandemic: a retrospective investigation of US hospitals’ CMS Star Ratings and 30-day mortality during the early pandemic
Authors: Pollock Benjamin D , Devkaran Subashnie , Dowdy Sean C
Published: February 2024

Objectives

In the USA and UK, pandemic-era outcome data have been excluded from hospital rankings and pay-for-performance programmes. We assessed the relationship between US hospitals’ pre-pandemic Centers for Medicare and Medicaid Services (CMS) Overall Hospital Star ratings and early pandemic 30-day mortality among both patients with COVID and non-COVID to understand whether pre-existing structures, processes and outcomes related to quality enabled greater pandemic resiliency.

Design and data source

A retrospective, claim-based data study using the 100% Inpatient Standard Analytic File and Medicare Beneficiary Summary File including all US Medicare Fee-for-Service inpatient encounters from 1 April 2020 to 30 November 2020 linked with the CMS Hospital Star Ratings using six-digit CMS provider IDs.

Outcome measure

The outcome was risk-adjusted 30-day mortality. We used multivariate logistic regression adjusting for age, sex, Elixhauser mortality index, US Census Region, month, hospital-specific January 2020 CMS Star rating (1–5 stars), COVID diagnosis (U07.1) and COVID diagnosis×CMS Star Rating interaction.

Results

We included 4 473 390 Medicare encounters from 2533 hospitals, with 92 896 (28.2%) mortalities among COVID-19 encounters and 387 029 (9.3%) mortalities among non-COVID encounters. There was significantly greater odds of mortality as CMS Star Ratings decreased, with 18% (95% CI 15% to 22%; p<0.0001), 33% (95% CI 30% to 37%; p<0.0001), 38% (95% CI 34% to 42%; p<0.0001) and 60% (95% CI 55% to 66%; p<0.0001), greater odds of COVID mortality comparing 4-star, 3-star, 2-star and 1-star hospitals (respectively) to 5-star hospitals. Among non-COVID encounters, there were 17% (95% CI 16% to 19%; p<0.0001), 24% (95% CI 23% to 26%; p<0.0001), 32% (95% CI 30% to 33%; p<0.0001) and 40% (95% CI 38% to 42%; p<0.0001) greater odds of mortality at 4-star, 3-star, 2-star and 1-star hospitals (respectively) as compared with 5-star hospitals.

Conclusion

Our results support a need to further understand how quality outcomes were maintained during the pandemic. Valuable insights can be gained by including the reporting of risk-adjusted pandemic era hospital quality outcomes for high and low performing hospitals.
Association between perioperative glucose proﬁles assessed by the continuous glucose monitoring (CGM) system and prognosis in patients with ST-segment elevation myocardial infarction (STEMI): protocol for a cohort study
Authors: Shi Jie , Wang Xulin , Zhang Hongqiang , Ding Yu , Wu Jiawei , Luo Sihui , Hu Hao , Zheng Xueying
Published: February 2024

Introduction

ST-segment elevation myocardial infarction (STEMI) presents a serious cardiovascular condition requiring prompt intervention. Dysglycaemia has been identified as a significant risk factor impacting STEMI prognosis. However, limited research has focused on comprehensively examining the association between glucose dynamics during the perioperative period and patient outcomes. This study aims to address this gap by leveraging continuous glucose monitoring (CGM) technology to gain real-time insights into glucose fluctuations and their potential impact on STEMI prognosis.

Methods and analysis

This is a multicentre, prospective, 3-year follow-up cohort study. Between May 2023 and May 2024, 550 eligible STEM patients who underwent percutaneous coronary intervention are expected to be recruited. Using the CGM system, continuous glucose levels will be collected throughout the perioperative phase. Key clinical parameters, including cardiac biomarkers, angiographic findings and major adverse cardiovascular events, will be assessed in relation to glucose profile.

Ethics and dissemination

The study was approved by the Medical Research Ethics Committee of The First Affiliated Hospital of University of Science and Technology of China and will be conducted in accordance with the moral, ethical and scientific principles of the Declaration of Helsinki. Written informed consent will be obtained from all participants before any study-related procedures are implemented. Study results will be disseminated through conferences and peer-reviewed scientific journals.

Trial registration number

ChiCTR2300069662.
RECITAL: a non-inferiority randomised control trial evaluating a virtual fracture clinic compared with in-person care for people with simple fractures (study protocol)
Authors: Teng Min Jiat , Zadro Joshua R , Pickles Kristen , Copp Tessa , Shaw Miranda J , Khoudair Isabella , Horsley Mark , Warnock Benjamin , Hutchings Owen R , Petchell Jeffrey F , Ackerman Ilana N , Drayton Alison , Liu Rong , Maher Christopher G , Traeger Adrian C
Published: February 2024

Introduction

Most simple undisplaced fractures can be managed without surgery by immobilising the limb with a splint, prescribing medication for pain, and providing advice and early rehabilitation. Recent systematic reviews based on retrospective observational studies have reported that virtual fracture clinics can deliver follow-up care that is safe and cost-effective. However, no randomised controlled trial has investigated if a virtual fracture clinic can provide non-inferior physical function outcomes compared with an in-person clinic for patients with simple fractures.

Methods and analysis

312 participants will be recruited from 2 metropolitan hospitals located in Sydney, Australia. Adult patients will be eligible if they have an acute simple fracture that can be managed with a removable splint and is deemed appropriate for follow-up at either the virtual or in-person fracture clinic by an orthopaedic doctor. Patients will not be eligible if they have a complex fracture that requires a cast or surgery. Eligible participants will be randomised to receive their follow-up care either at the virtual or the in-person fracture clinic. Participants at the virtual fracture clinic will be reviewed within 5 days of receiving a referral through video calls with a physiotherapist. Participants at the in-person fracture clinic will be reviewed by an orthopaedic doctor within 7–10 days of receiving a referral. The primary outcome will be the patient’s function measured using the Patient-Specific Functional Scale at 12 weeks. Secondary outcomes will include health-related quality of life, patient-reported experiences, pain, health cost, healthcare utilisation, medication use, adverse events, emergency department representations and surgery.

Ethics and dissemination

The study has been approved by the Sydney Local Health District Ethics Review Committee (RPAH Zone) (X23-0200 and 2023/ETH01038). The trial results will be submitted for publication in a reputable international journal and will be presented at professional conferences.

Trial registration number

ACTRN12623000934640.
Perceptions of Australia’s e-cigarette regulations and recommendations for future reforms: a qualitative study of adolescents and adults
Authors: Brierley Mary-Ellen E , Yaw Sean J L , Jongenelis Michelle I
Published: February 2024

Objective

To assess public perceptions of the effectiveness of e-cigarette regulations in minimising use among adolescents and those who have never smoked. Specifically, we explored (1) perceived effectiveness of current regulations relating to e-cigarettes and (2) ideas for further regulations that could reduce use.

Design and participants

Focus groups (n=16) were conducted with Australian adolescents (14–17 years), young adults (18–24 years) and adults (25–39 years). Groups were stratified by age, gender and e-cigarette use status. Data were analysed using reflexive thematic analysis.

Setting

Focus groups were conducted in-person in two major Australian cities.

Results

Groups lacked a comprehensive understanding of e-cigarette regulations in Australia. When informed of these regulations, half of the groups considered the prescription model for nicotine e-cigarette products to be effective when enforced appropriately. Almost all groups considered access to non-nicotine products problematic. All groups suggested a range of demand reduction regulations, including plain packaging, health warnings, flavour restrictions and increased vape-free areas. Most groups (predominantly those who had never vaped) also recommended supply reduction regulations such as banning all e-cigarettes. The need for supply reduction measures to include addiction and mental health supports was discussed.

Conclusions

The regulations recommended by participants largely align with those that are to be introduced in Australia, indicating that these reforms are likely to be accepted by the public. Ensuring these reforms are complemented by formal supports for young people experiencing nicotine dependence and related mental health concerns is critical.
Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial
Authors: Brittain Gavin , Petrie Jennifer , Duffy Kate E M , Glover Rachel , Hullock Katie , Papaioannou Diana , Roldan Elisa , Beecher Colette , Bursnall Matthew , Ciccarelli Olga , Coles Alasdair J , Cooper Cindy , Giovannoni Gavin , Gabriel Ian , Kazmi Majid , Kyriakou Charalampia , Nicholas Richard , Paling David , Peniket Andy , Scolding Neil , Silber Eli , de Silva Thushan , Venneri Annalena , Walters Stephen J , Young Carolyn , Muraro Paolo A , Sharrack Basil , Snowden John A
Published: February 2024

Introduction

Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, ‘Multiple Sclerosis International Stem Cell Transplant, MIST’, showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS.

Methods and analysis

StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve ‘no evidence of disease activity’ during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs.

Ethics and dissemination

The study was approved by the Yorkshire and Humber—Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences.

Trial registration number

ISRCTN88667898.
Leisure time physical activity is associated with improved diastolic heart function and is partly mediated by unsupervised quantified metabolic health
Authors: Klarenberg Hugo , van der Velde Jeroen HPM , Peeters Carel FW , Dekkers Ilona A , de Mutsert R , Jukema J Wouter , Rosendaal Frits R , Leiner Tim , Froeling Martijn , Jorstad Harald , Boekholdt S Matthijs , Strijkers Gustav J , Lamb Hildo J
Published: February 2024

Objectives

To investigate the association between leisure time physical activity (LTPA) and MRI-based diastolic function and the mediating role of metabolic health.

Methods

This cross-sectional analysis comprised 901 participants (46% women, mean age (SD): 56 (6) years (The Netherlands, 2008–2012)). LTPA was assessed via questionnaire, quantified in metabolic equivalent of tasks (METs)-minutes per week and participants underwent abdominal and cardiovascular MRI. Confirmatory factor analysis was used to construct the metabolic load factor. Piecewise structural equation model with adjustments for confounders was used to determine associations between LTPA and diastolic function and the mediating effect of metabolic load.

Results

Significant differences in mitral early/late peak filling rate (E/A) ratio per SD of LTPA (men=1999, women=1870 MET-min/week) of 0.18, (95% CI= 0.03 to 0.33, p=0.021) were observed in men, but not in women: −0.01 (−0.01 to 0.34, p=0.058). Difference in deceleration time of mitral early filling (E-DT) was 0.13 (0.01 to 0.24, p=0.030) in men and 0.17 (0.05 to 0.28, p=0.005) in women. Metabolic load, including MRI-based visceral and subcutaneous adipose tissue, fasting glucose, high-density lipoprotein cholesterol and triglycerides, mediated these associations as follows: E/A-ratio of 0.030 (0.000 to 0.067, 19% mediated, p=0.047) in men but not in women: 0.058 (0.027 to 0.089, p<0.001) and E-DT not in men 0.004 (−0.012 to 0.021, p=0.602) but did in women 0.044 (0.013 to 0.057, 27% mediated, p=0.006).

Conclusions

A larger amount of LTPA was associated with improved diastolic function where confirmatory factor analysis-based metabolic load partly mediated this effect. Future studies should assess whether improving indicators of metabolic load alongside LTPA will benefit healthy diastolic function even more.
Stress urinary incontinence prevalence and risk factors in female rugby players: a common health problem across four nations
Authors: McCarthy-Ryan Molly , Perkins Joanna , Donnelly Gráinne M , Caithriona Yeomans , Liston Mairead , Leahy Karina , Bø Kari , O'Halloran Patrick , Moore Isabel S
Published: February 2024

Objectives

Female athletes engaging in high-impact sports have a higher prevalence of experiencing stress urinary incontinence (SUI). However, the prevalence of sport-specific SUI and associated risk factors in female rugby players is relatively unknown. We aimed to determine the prevalence of general and rugby-related SUI and identify associated risk factors and inciting events in female rugby players.

Methods

Observational, cross-sectional study of 396 female rugby players (age 28±8 years, mass 80±18 kg, height 1.90±0.19 m, playing years 7±6 years) participating in rugby across UK and Ireland completed an electronic questionnaire regardless of SUI status.

Results

63 to 88% of players had SUI, and 43% had rugby-related SUI. There was an association with players reporting a change in incontinence status due to playing rugby (p<0.001). Players who experienced constipation (OR 2.33 (95% CI 1.49 to 3.66)), had given birth (OR 2.36 (95% CI 1.18 to 4.73)) or who had a higher body mass index (BMI) (OR 1.04 (95% CI 1.01 to 1.08)), were identified as having increased odds of rugby-related SUI. For rugby-specific risk factors, playing as a forward (OR 1.97 (95% CI 1.29 to 3.01)) increased the odds, whereas playing at a national compared with amateur level (OR 0.44 (95% CI 0.20 to 0.97)) decreased the odds of rugby-related SUI. The most prevalent inciting SUI events were being tackled (75%), tackling (66%), running (63%) and jumping/landing (59%).

Conclusion

Rugby-related SUI was prevalent in female rugby players. Risk factors were having constipation, a high BMI, being postpartum, playing position and level. Player welfare strategies addressing pelvic floor dysfunction and postpartum rehabilitation are warranted.
Beyond coercion: reframing the influencing other in medically assisted death
Authors: Buchbinder Mara , Berens Noah
Published: February 2024

This essay considers how we are to understand the decision to end one’s life under medical aid-in-dying (MAID) statutes and the role of influencing others. Bioethical concerns about the potential for abuse in MAID have focused predominantly on the risk of coercion and other forms of undue influence. Most bioethical analyses of relational influences in MAID have been made by opponents of MAID, who argue that MAID is unethical, in part, because it cannot cleanly accommodate relational influences. In contrast, proponents of MAID have downplayed the role of relational influences because they may threaten the pillars of autonomy and voluntariness on which the ethics of MAID rest. Drawing on a case study collected as part of an ethnographic study of MAID in Vermont, we show how relations of care are central to MAID decision-making. Such relations may muddle motives for assisted death, exposing the limits of conventional bioethics thinking on MAID and relational influence. Here, we argue that ethical frameworks for MAID should account for the role of relational influences in decision-making, and acknowledge that relational influences may support, as well as undermine, a decision for MAID. We then outline an evaluative framework for determining whether relational influences are undue that identifies six key domains for consideration: mental competence, authenticity, relationship context, having an adequate range options, financial considerations and irremediability. We conclude by suggesting that social relationships may constitute an important source of value in end-of-life decision-making and not only a liability.
Evaluating the spatial transferability of habitat suitability models: implications for conservation and management
Authors: Linner Robyn M. , Chen Yong
Published: February 2024

Habitat models often rely on data with incomplete or patchy survey coverage, making it necessary to project observed habitat relationships into unsampled areas. Model transferability is often assumed, rarely tested, and may result in uninformed management recommendations if not validated. In the eastern Gulf of Maine, data from the federal trawl survey has historically been used to identify suitable habitat for juvenile Atlantic cod ( Gadus morhua), despite mainly sampling in offshore waters. This study evaluated the spatial transferability of a habitat suitability index model by projecting offshore habitat relationships inshore and comparing them to models built using two inshore surveys. Due to rare warm-water exposure in offshore waters, the federal survey model was unable to identify suitable habitat in the warmer, shallower areas that the inshore surveys identified, suggesting that offshore models are not transferable inshore for juvenile cod in the eastern Gulf of Maine. The results of this study have implications for fisheries worldwide and suggest that incorrectly assuming model transferability could pose a significant hurdle for effective conservation and management.
Toward the development of an ecosystem model ensemble to support adaptive management in Lake Ontario
Authors: Neumann Alex , Fernando Yasasi , Saber Ali , Arhonditsis George B.
Published: February 2024

Notwithstanding the continuing advancement of our understanding of the broader ecosystem functioning in Lake Ontario, emerging evidence suggests that there are fundamental knowledge gaps to accurately describe the relationship between exogenous phosphorus (P) loading and in-lake total phosphorus (TP) concentrations. The whole-lake load appears to frequently exceed the Great Lakes Water Quality Agreement (GLWQA) interim target of 7000 metric tonnes·year−1, although the offshore-water P concentrations are consistently below the GLWQA interim substance concentration objective of 10 µg TP·L–1. Contrasting ecological conditions prevail in different locations of Lake Ontario, owing to the significant urban footprint along the shoreline but also the capacity of dreissenid mussels to sequester P in the littoral zone. Specifically, low ambient P levels threaten fisheries productivity in offshore waters, while nuisance benthic algae (predominantly Cladophora) and toxin-producing cyanobacteria blooms affect the water quality in the nearshore zone. The present study offers a technical analysis of the recent and ongoing modelling work that has been conducted in Lake Ontario and can be potentially used to address the multitude of ecosystem management challenges. Our aim is to provide an overview of all the major models developed by identifying their fundamental assumptions, structural attributes, and general consistency against empirical knowledge derived from the system. The existing modelling work has opted for parsimonious representations of the lower food web coupled with granular grid configurations to effectively link hydrodynamic processes and mass transport between nearshore and offshore waters. The establishment of comprehensive ecophysiological modules that will recreate the mechanisms underlying the interplay among bioavailable phosphorus, planktonic dynamics, dreissenid mussels, and Cladophora is a critical undertaking to reproduce the water quality conditions in the nearshore zone of Lake Ontario. Striving to integrate the lower food web with fisheries and ecosystem-service modelling, we also offer a technical analysis of knowledge gaps and monitoring-assessment objectives that should be addressed to ensure that ecosystem processes of management interest are adequately measured and the local modelling enterprise is focused on suitable performance indicators.