bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved lipid-facing basic residues promote the insertion of the porin OmpC into the
E. coli
outer membrane
Authors: Peterson Janine H. , Yang Lixinhao , Gumbart James C. , Bernstein Harris D. 
Published: February 2025

ABSTRACT

Almost all integral membrane proteins that reside in the outer membrane (OM) of gram-negative bacteria contain a closed amphipathic β sheet (“β barrel”) that serves as a membrane anchor. The membrane integration of β barrel structures is catalyzed by a highly conserved heterooligomer called the
b
arrel
a
ssembly
m
achine (BAM). Although charged residues that are exposed to the lipid bilayer are infrequently found in outer membrane protein β barrels, the β barrels of OmpC/OmpF-type trimeric porins produced by Enterobacterales contain multiple conserved lipid-facing basic residues located near the extracellular side of the OM. Here, we show that these residues are required for the efficient insertion of the
Escherichia coli
OmpC protein into the OM
in vivo
. We found that the mutation of multiple basic residues to glutamine or alanine slowed insertion and reduced insertion efficiency. Furthermore, molecular dynamics simulations provided evidence that the basic residues promote the formation of hydrogen bonds and salt bridges with lipopolysaccharide, a unique glycolipid located exclusively in the outer leaflet of the OM. Taken together, our results support a model in which hydrophilic interactions between OmpC and LPS help to anchor the protein in the OM when the local environment is perturbed by BAM during membrane insertion and suggest a surprising role for membrane lipids in the insertion reaction.

IMPORTANCE

The assembly (folding and membrane insertion) of bacterial outer membrane proteins (OMPs) is an essential cellular process that is a potential target for novel antibiotics. A heterooligomer called the
b
arrel
a
ssembly
m
achine (BAM) plays a major role in catalyzing OMP assembly. Here, we show that a group of highly conserved lipid-facing basic residues in
Escherichia coli
OmpC, a member of a major family of abundant OMPs known as trimeric porins, is required for the efficient integration of the protein into the outer membrane (OM). Based on our work and previous studies, we propose that the basic residues form interactions with a unique OM lipid (lipopolysaccharide) that promotes the insertion reaction. Our results provide strong evidence that interactions between specific membrane lipids and at least a subset of OMPs are required to supplement the activity of BAM and facilitate the integration of the proteins into the membrane.
Depression, reduced physical activity and the risk of heart disease: a prospective cohort of European middle-aged and older adults
Authors: Peralta Miguel , Nascimento Marcelo , Ferrari Gerson , Gouveia Élvio R , Marques Adilson 
Published: February 2025

ObjectiveTo assess the impact of depression and physical activity (PA) of different intensities on the incidence of heart disease.MethodsA prospective cohort study with 20 645 European middle-aged and older adults (mean baseline age 63 years; 55.1% women; median follow-up 9.5 years) was conducted using data from the Survey of Health, Ageing and Retirement in Europe. The EURO-D 12-item scale assessed depression. Moderate-intensity and vigorous-intensity PA and heart disease diagnoses were self-reported. We classified participants into the following four groups: (1) depression plus low PA, (2) no depression plus low PA, (3) depression plus moderate/high PA, (4) no depression plus moderate/high PA. Hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazards models adjusted for confounders.ResultsCompared with having depression and low PA levels, adjusted HR for heart disease similarly decreased for participants with depression and moderate/high PA (moderate-intensity PA: HR=0.63, 95% CI=0.50, 0.78; vigorous-intensity PA: HR=0.69, 95% CI=0.53, 0.89) and participants without depression and low PA (moderate-intensity PA: HR=0.64, 95% CI=0.50, 0.82; vigorous-intensity PA: HR=0.68, 95% CI=0.58, 0.80). The greatest risk reduction was found in participants without depression and moderate/high PA (moderate-intensity PA: HR=0.46, 95% CI=0.37, 0.55; vigorous-intensity PA: HR=0.48, 95% CI=0.40, 0.58).ConclusionModerate-intensity and vigorous-intensity PA seems to counteract the increased risk for heart disease associated with depression. This highlights the importance of PA as a possible intervention strategy aiming to manage the risk of heart disease among people with depression.
Prevalence of psychiatric disorders during pregnancy—a feasibility study at second trimester ultrasound in the general population (GROUP study): study protocol
Authors: Knabe Lucie , Tanaka Camille , Tebeka Sarah , Neilson Samantha , Cauvin Clothilde , Mercier Nicolas , Cayron Daphné , Savelli Morane , Deruelle Philippe , Fuchs Florent , Pissarra Joana , Molinari Nicolas , Belzeaux Raoul 
Published: February 2025

IntroductionDuring the perinatal period, women have an increased risk for psychiatric disorders, which are highly prevalent in this context. In addition, there are significant delays in diagnosing these conditions, worsening their prognosis and increasing their societal burden. Studies describing psychiatric disorders in the perinatal period often focus on specific disorders; only postpartum depression and, to a lesser extent, anxiety disorders are studied. There are also very few evaluations conducted by clinicians based on a semistructured interview, relying on the diagnostic criteria of international nosography.Methods and analysisThis multicentric prospective study will recruit 140 adult pregnant women based on randomly selected second trimester (T2) ultrasound consultations. The primary outcome is the prevalence of any psychiatric disorder assessed with a standardised psychiatric assessment, the Mini-International Neuropsychiatric Interview (M.I.N.I.). Within 10 days after the T2 ultrasound appointment, we will conduct the M.I.N.I., collect demographic data, evaluate suicidal behaviour with the Columbia-Suicide Severity Rating Scale, describe negative life events from the past year using the Paykel questionnaire and evaluation of social deprivation (Evaluation of the Deprivation and Inequalities of Health in Healthcare Centres score). Participants will also complete self-administered psychiatric questionnaires that screen for specific pathologies. We will build a biological sample collection. At two months post partum, we will repeat the questionnaires, adding an assessment of mother-child bonding. Patients can choose between in-person or telemedicine visits on both occasions.Ethics and disseminationAll participants will be required to provide written informed consent. The study has received ethical approval from the French National Committee (‘Comité de Protection des Personnes Ouest VI’) (approval number: 23.03919.000236). Results will be disseminated through peer-reviewed journal publications and at scientific conferences and meetings.Trial registration numberNCT06297252.
Understanding how midwife-led continuity of care can be implemented and under what circumstances: a realist review
Authors: Simmelink Renate , Neppelenbroek Elise , Pouwels Anneke , van der Lee Nadine , Pajkrt Eva , Ziesemer Kirsten A , Harmsen van der Vliet-Torij Hanneke W , Verhoeven Corine J M , de Jonge Ank , Nieuwenhuijze Marianne 
Published: February 2025

ObjectivesTo understand how and under what circumstances midwife-led continuity of care (MLCC) can be implemented in high-income countries.DesignA realist review was conducted to examine interactions between contexts, mechanisms and outcomes.MethodsAn initial programme theory described a hypothesis of how MLCC might be implemented successfully. Literature from a systematic search on the implementation of MLCC was synthesised and supplemented with unstructured searches to identify literature that reinforced the emerging concepts. The synthesis was an iterative process, endorsed in consultation with stakeholders, leading to a refined programme theory.ResultsA total of 45 documents were included. The mechanisms identified can be grouped around macrolevel challenges, leadership, role ambiguity and conflict, and personal and professional boundaries. Despite strong evidence supporting MLCC, diverse stakeholder interests and power dynamics hinder its implementation. Implementing MLCC disrupts established roles and power structures, creating uncertainty and anxiety at all levels. To successfully navigate healthcare providers through the transition, both formal and informal leaders must demonstrate the courage and vision to challenge existing norms.ConclusionsRealist methodology allowed the identification of mechanisms that often remain unnoticed but significantly impact the implementation of MLCC. Concrete policies and guidelines are essential to ensure consistency in care delivery. Collaborative efforts and a shared philosophy among all stakeholders, combined with strong leadership that builds trust and addresses anxiety, can create a supportive environment for MLCC implementation.PROSPERO registration numberCRD42023446437.
Effects of transcutaneous auricular vagus nerve stimulation on postoperative delirium in older patients with hip fracture: protocol for a randomised controlled trial
Authors: Zhou Hongyan , Song Ailin , Zhang Hui , Zhang Liang 
Published: February 2025

BackgroundPostoperative delirium (POD) is an acute neurocognitive impairment and is commonly observed in older patients with hip fractures. POD is associated with poor outcomes, including increased postoperative complications, prolonged hospitalisation, high costs and increased perioperative mortality. Therefore, reducing the occurrence of POD and improving cognitive abilities in older patients are critical and urgent. Transcutaneous auricular vagus nerve stimulation (TAVNS) is a simple, safe, non-invasive treatment and has great potential to improve cognitive function. This clinical study will evaluate the effectiveness of TAVNS in reducing the incidence of POD in older patients and further elucidate the possible underlying mechanisms.Methods and analysisThis randomised, double-blind, single-centre controlled trial will enroll 154 older patients undergoing hip fracture surgery, who will be randomly assigned to the TAVNS group (n=77), receiving TAVNS from 1 hour before anaesthetic induction to the end of the surgery, or the sham stimulation group (n=77), receiving sham stimulation in the same manner. The primary outcome measure will be the incidence of POD during the first 7 days post-surgery, as assessed by the confusion assessment method for the intensive care unit. The secondary outcomes include the incidence of delayed neurocognitive recovery; serum acetylcholinesterase and butyrylcholinesterase levels; the concentrations of tumour necrosis factor-α, interleukin-1β, interleukin-6 and S100β; unplanned intensive care unit admission rates; the length and cost of hospital stay; the incidence of postoperative complications during hospitalisation; and mortality at 1 month, 6 months and 1 year after surgery.Ethics and disseminationThis study was approved by the Ethics Committee of the Chongqing Traditional Chinese Medicine Hospital on 15 May 2024 (2024-KY-HY-13). The findings will be published in the international peer-reviewed academic journals and presented orally at academic conferences.Trial registration numberChiCTR2400085508.
Impact of an acute 1-month cannabidiol treatment on pain and inflammation after a long bone fracture: a triple-blind randomised, placebo-controlled, clinical trial protocol
Authors: Brazeau Daphnée , Deshaies Amelie A , Williamson David , Bernard Francis , Arbour Caroline , Pinard Anne Marie , Rouleau Dominique , De Beaumont Louis 
Published: February 2025

IntroductionAcute pain levels following orthopaedic injury (eg, fracture) are a predictor of the onset of chronic pain, which affects nearly 50% of fracture patients and impairs functional recovery. Among current pharmacological treatments for acute pain, non-steroidal anti-inflammatory drugs have been associated with delayed bone healing, while opioids inhibit effective bone remodelling, increase the risk of pseudarthrosis and carry a high risk of addiction. In light of this, the development of new pain treatments is essential. Cannabidiol (CBD), a non-addictive and non-psychotropic cannabis component stands out as a potential therapeutic agent, given its analgesic and anti-inflammatory properties as well as its potential benefits for bone healing. This randomised controlled trial aims to investigate the effect of acute CBD treatment, compared with placebo, on patients’ self-reported pain, inflammation and well-being following a fracture injury.Methods and analysisThis is a triple-blind, randomised, placebo-controlled clinical trial. A total of 225 adults aged 18–70 years, who have suffered a long bone fracture and were treated at the Hôpital du Sacré-Coeur de Montréal, will be randomly assigned within 1 week to one of three treatment arms (25 mg or 50 mg of CBD or placebo) for 1 month. The primary outcome will be the difference in the pain score between groups at 1-month follow-up. Secondary outcomes will include measures of persistent pain, inflammation, opioid usage, quality of life, sleep quality, depression, anxiety, cognition and orthopaedic function. Data will be collected at baseline, 1-month and 3-month follow-ups.Ethics and disseminationThis study obtained a Health Canada licence for use of cannabis products. It has also been approved by Health Canada and the Research Ethics Board of the CIUSSS du Nord-de-l’Île-de-Montréal (Project ID 2025-2105). The findings will be published in a peer-reviewed journal and presented at local, national and international conferences. The trial’s results will be made publicly available on the ClinicalTrials.gov database.Trial registration numberNCT06448923.
Exploring barriers, motivators and facilitators for physical activity and exercise in a UK South Asian community: a qualitative study
Authors: Deshmukh Ashwini , Kumar Kanta , Quinlan Jonathan 
Published: February 2025

ObjectivesThis study aimed to elucidate motivators, barriers and facilitators of physical activity (PA) and exercise in a UK adult South Asian (SA) population. In addition, we sought to understand the sources of information regarding PA and the awareness of UK PA guidelines. Finally, the study aimed to explore public understanding of the utility of exercise for health outcomes and the role in disease prevention.DesignExplorative study using qualitative research methods including interviews and self-determination theory.SettingBirmingham, UK.ParticipantsThe study included 15 UK SA adults (8 male, 7 female) with a mean age of 53.1 years (SA defined as Indian, Pakistani, Bangladeshi or Sri Lankan).ResultsWe here found three key themes: (1) Engagement in PA and exercise, (2) Factors influencing PA and exercise (both barriers and facilitators) and (3) Accessibility to information. Participants showed a thorough understanding of PA; however, they lacked knowledge of strength-building exercise (ie, resistance exercise). This was particularly evident in SA women. Barriers to exercise typically focused around concepts of time, while facilitators centred on sufficient support. Knowledge of PA and exercise was typically obtained via social media, with only 2/15 aware of UK guidelines.ConclusionsWhile SA adults were aware of the importance of PA and its utility in health prevention, there was an evident lack of knowledge of guidelines and in particular the need for resistance exercise or other strength-building activities. We highlight a need to develop new routes to disseminate information within the SA population to increase knowledge and understanding of PA and resistance exercise for overall health.
Prevalence of dry eye disease among children: a systematic review and meta-analysis
Authors: Zou Yuhao , Li Dongfeng , Gianni Virgili , Congdon Nathan , Piyasena Prabhath , Prakalapakorn S Grace , Zhang Ruifan , Zhao Zixiang , Chan Ving Fai , Yu Man 
Published: February 2025

BackgroundDry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface instability that causes ocular discomfort and visual impairment. The increasing use of digital devices and changing lifestyle patterns have raised concerns about a potential rise in DED among children. Understanding the prevalence of paediatric DED is crucial for developing effective diagnostic and management strategies tailored to this vulnerable population.MethodAn exhaustive literature search was performed on several databases covering the period from 1 January 2001 to 1 April 2024. Prevalence estimates of DED were combined using random effects models, and heterogeneity sources were explored through subgroup and regression analyses.ResultsOur literature search identified 7309 articles, of which 41 articles, representing 42 study cohorts (48 479 participants) included in the systematic review. The estimated prevalence of DED among children was 23.7% (95% CI 18.5% to 28.9%). The prevalence of DED by different diagnostic criteria (clinical signs vs reported symptoms by questionnaire) was 16.6% (95% CI 13.7% to 19.5%; 26 studies; 27 107 children) vs 34.6% (95% CI 23.7% to 45.6%; 16 studies; 21 372 children; p<0.01), respectively. The prevalence of DED after the COVID-19 pandemic outbreak was 44.1% (95% CI 25.5% to 62.7%; 8 studies; 9163 children), which was significantly higher than the 18.7% (95% CI 15.6% to 21.9%; 34studies, 39 316 children; p=0.01) before the COVID-19 outbreak. High between-study heterogeneity was noted (I2>92%). In meta-regression analysis, the prevalence of DED among children increased by 7.1% with each 10° decrease in latitude (p=0.015), and by 10.2% with each 10° increase in mean annual temperature (p=0.024).ConclusionsDED is common in children up to 18 years of age and poses a significant disease burden. Standardisation of the diagnosis of DED in children and further study of other risk factors are needed to fully explain the epidemiology of DED in children.
Broadening the definition of patient-safety events: lessons from a multicentre learning health system collaborative
Authors: Huddleston Jeanne M , Whitford Daniel , Yaszemski Alexandra K , Schrieber Matthew P , Pollak Edward 
Published: February 2025

BackgroundImproving safety in healthcare has been paramount for decades, yet despite major attention and investment, improvement has remained incremental. Patient safety is a major concern in US healthcare, leading to significant harm and economic losses annually. Accurately identifying safety events remains difficult due to methodological discrepancies and lack of standardisation. This study evaluated the feasibility of implementing a standardised case-review methodology and safety-event taxonomy across diverse hospital settings to assess opportunities for improvement (OFIs) and compare findings with traditional definitions.MethodsThis multicentre retrospective cohort study reports data from 103 hospitals across the USA and Canada between 2016 and 2023. A multivariable logistic regression was performed to test case reviews for differences in the presence of one or more OFIs across several hospital types (bed size, academic status, urban setting, trauma level and Centres for Medicare and Medicaid Services overall star rating) and patient characteristics (age, gender, length of stay, admission and discharge code status and mortality).Results19 181 cases were reviewed across the Learning Health System Collaborative, with a median of 107 reviews per hospital. Mortality was the most common cohort selection, studied by 91 hospitals (88%). At least one OFI was identified in 12 714 cases (66.3%). The logistic regression analysis found that all hospital characteristics and patient age, length of stay, code status and discharge disposition were significantly associated with at least one OFI. Of the 46 444 OFIs identified, 41 439 (89%) were from categories focused on omissions of care. The categories of end-of-life, documentation and treatment/care alone accounted for 25 980 OFIs (56%).ConclusionThe highest volumes of safety-related OFIs were associated with omissions of care, as opposed to the traditional definition of patient safety, which primarily includes outcomes from acts of commission.
Reduced wait times for molecular-biomarker testing among patients with advanced lung cancer using parallel sample processing and closed-loop communication: the Continuous Oncopanel and ALK Status Tracking (COAST) Project
Authors: Yeo Sarah , Sun Jane , Zibrik Kelly , Shaipanich Tawimas , Carolan Hannah , Melosky Barbara , Ionescu Diana , Alex Deepu , Yip Stephen , Wang Ying 
Published: February 2025

BackgroundGiven how crucial molecular-biomarker testing is to treatment decisions for advanced non-small cell lung cancer (NSCLC), guidelines recommend a turnaround time (TAT) of 14 calendar days from receiving specimen to test result, and 3 days to receive a specimen from outside pathology lab. Current TAT for molecular-biomarker testing in British Columbia (BC), Canada frequently exceeds these recommendations. Thus, we launched a quality improvement (QI) initiative to improve TAT of molecular-biomarker testing.MethodsWe assembled a multidisciplinary team to identify areas contributing to delays in molecular-biomarker testing. We designed and conducted three Plan-Do-Study-Act (PDSA) cycles. Cycles 1 and 2 involved changing requisition delivery method from fax to email between BC Cancer Vancouver Centre (BCCV) and two outside hospitals with the highest volume of specimens. Cycle 3 introduced parallel processing of specimens at BCCV pathology lab and concurrent molecular-biomarker testing. TAT was evaluated before and after these process changes along with staff satisfaction via survey.ResultsThe average TAT from test request to specimen received by BCCV was reduced from 6.4 days prechange to 4.6 days postchange. The TAT from specimen receipt by BCCV to report availability was reduced from a median of 22–16 days. Report availability for initial medical oncology consultation increased from a median of 13%–29%. The staff satisfaction survey revealed an enhanced experience with the new process, particularly for our nurse navigator.ConclusionThe TAT for molecular-biomarker testing is an ongoing and complex challenge for healthcare systems worldwide. This QI project is a step towards addressing province-wide reduction in wait times for molecular-biomarker testing results in BC. We continue to explore further ideas to improve workflow metrics and patient care among patients with advanced NSCLC.