bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of cyclic diguanylate-modulating proteins in
Vibrio fischeri
Authors: Isenberg Ruth Y. , Holschbach Chandler S. , Gao Jing , Mandel Mark J. 
Published: October 2024

ABSTRACT

As bacterial symbionts transition from a motile free-living state to a sessile biofilm state, they must coordinate behavior changes suitable to each lifestyle. Cyclic diguanylate (c-di-GMP) is an intracellular signaling molecule that can regulate this transition, and it is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. Generally, c-di-GMP inhibits motility and promotes biofilm formation. While c-di-GMP and the enzymes that contribute to its metabolism have been well studied in pathogens, considerably less focus has been placed on c-di-GMP regulation in beneficial symbionts.
Vibrio fischeri
is the sole beneficial symbiont of the Hawaiian bobtail squid (
Euprymna scolopes
) light organ, and the bacterium requires both motility and biofilm formation to efficiently colonize. c-di-GMP regulates swimming motility and cellulose exopolysaccharide production in
V. fischeri
. The genome encodes 50 DGCs and PDEs, and while a few of these proteins have been characterized, the majority have not undergone comprehensive characterization. In this study, we use protein overexpression to systematically characterize the functional potential of all 50
V
.
fischeri
proteins. All 28 predicted DGCs and 10 of the 14 predicted PDEs displayed at least one phenotype consistent with their predicted function, and a majority of each displayed multiple phenotypes. Finally, active site mutant analysis of proteins with the potential for both DGC and PDE activities revealed potential activities for these proteins. This work presents a systems-level functional analysis of a family of signaling proteins in a tractable animal symbiont and will inform future efforts to characterize the roles of individual proteins during lifestyle transitions.

IMPORTANCE

Cyclic diguanylate (c-di-GMP) is a critical second messenger that mediates bacterial behaviors, and
Vibrio fischeri
colonization of its Hawaiian bobtail squid host presents a tractable model in which to interrogate the role of c-di-GMP during animal colonization. This work provides systems-level characterization of the 50 proteins predicted to modulate c-di-GMP levels. By combining multiple assays, we generated a rich understanding of which proteins have the capacity to influence c-di-GMP levels and behaviors. Our functional approach yielded insights into how proteins with domains to both synthesize and degrade c-di-GMP may impact bacterial behaviors. Finally, we integrated published data to provide a broader picture of each of the 50 proteins analyzed. This study will inform future work to define specific pathways by which c-di-GMP regulates symbiotic behaviors and transitions.
Supplemental Material: Petrogenetic relationship of the variably Ni–Cu–platinum-group element (PGE)-mineralized intrusions of the Thunder Bay North Intrusive Complex, Midcontinent Rift, Canada: Implications for mineral exploration in mafic–ultramafic complexes
Authors: Brzozowski Matthew J. , al. et 
Published: October 2024

<p>Text S1: Analytical methods and assessment of mineral fractionation on lambda values. Figure S1: Downhole variation diagram through the Southeast Anomaly illustrating the variation in MgO, Al<sub>2</sub>O<sub>3</sub>, TiO<sub>2</sub>, and Cr (from Brzozowski et al., 2023a), plus images of representative samples of mafic and ultramafic rocks from the Current intrusion. Figure S2: Chondrite-normalized REE profiles for the mafic–ultramafic rocks of the TBNIC and the country rocks. Figure S3: Binary diagrams illustrating the variations in εNd<sub>t</sub> and <sup>87</sup>Sr/<sup>86</sup>Sr<sub>i</sub> as a function of Th/La for the mafic–ultramafic rocks of the TBNIC and a metasedimentary country rock sample. Figure S4: Binary diagrams illustrating the variations in λ<sub>1</sub>–λ<sub>2</sub> of the mafic–ultramafic rocks of the TBNIC with MgO and λ<sub>0</sub>. Table S1: Bulk-rock geochemical data (raw) of mafic–ultramafic rocks of the TBNIC and associated country rocks. </p>
Maintaining non-communicable disease (NCD) services during the COVID-19 pandemic: lessons from Thailand
Authors: Coates Melanie , Cheh Paul Li Jen , Suenghataiphorn Thanathip , Laohavinij Wasin , Pholpark Aungsumalee , Ritthisirikul Natchaya , Khositchaiwat Sirithorn , Hanvoravongchai Piya 
Published: October 2024

The COVID-19 pandemic presented a significant challenge to health systems worldwide, requiring resources to be directed to the pandemic response while also maintaining essential health services. Those with non-communicable diseases (NCDs) are particularly vulnerable to COVID-19, and interrupted care resulting from the pandemic has the potential to worsen morbidity and mortality.We used narrative literature review and key informant interviews between August 2021 and June 2022 to identify how NCD services were impacted during the pandemic and which good practices helped support uninterrupted care.On the background of an existing strong healthcare system, Thailand exhibited strong central coordination of the response, minimised funding interruptions and leveraged existing infrastructure to make efficient use of limited resources, such as through mobilising healthcare workforce. A key intervention has been redesigning NCD systems such as through the ‘New Normal Medical Services’ initiative. This has promoted digital innovations, including remote self-monitoring, patient risk stratification and alternative medication dispensing. Emphasis has been placed on multidisciplinary, patient-centred and community-centred care.NCD service utilisation has been disrupted during the COVID-19 pandemic; however, newly adapted efforts on top of existing robust systems have been critical to mitigating disruptions. Yet challenges remain, including ensuring ongoing evaluation, adaptation and sustainability of redesign initiatives. This learning offers the potential to further positive health systems change on a wider scale, through sharing knowledge, international collaboration and further refinement of the ‘new normal’ model.
Safety and performance of the ultrathin sirolimus-eluting coronary stent in an all-comer patient population: the S-FLEX UK-II registry
Authors: Karthikeyan Vellore J , Mozid Abdul , Aggarwal Suneil , Kumar Abhishek , Hildick-Smith David , Anderson Richard , Nair Satheesh , Ruparelia Neil , Curzen Nick , Veerasamy Murugu , Elsheikh Sandra , Zaman Azfar 
Published: October 2024

ObjectiveWe evaluated the clinical safety and performance of the ultrathin strut biodegradable polymer-coated Supraflex Cruz (Sahajanand Medical TechnologiesLtd., Surat, India) sirolimus-eluting stent (SES) in an all-comer patient population requiring coronary stent implantation.Study designThe study was a prospective, observational, multicentre, single-arm registry.Study settingsThe study was conducted at 19 NHS Hospitals across the UK, from March 2020 to September 2021.Study participantsA total of 1904 patients with symptomatic coronary artery disease (age ≥18 years) who underwent percutaneous coronary intervention with at least one Supraflex Cruz SES were enrolled.Primary and secondary outcomes measureThe primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI) and clinically indicated target lesion revascularisation (CI-TLR), at 12 months. Safety endpoints were stent thrombosis, all-cause death and any MI. Prespecified subgroups analysis included patients with diabetes mellitus, bifurcation lesion, type B2/C lesion defined as per ACC/AHA (American College of Cardiology/American Heart Association) lesion classification and long coronary lesions (>20 mm).ResultsA total of 2973 Supraflex Cruz SES were implanted in 1835 patients (mean age: 65.20±11.03 years). Of these, 404 patients had diabetes mellitus (491 lesions), 271 had bifurcation lesions (293 lesions), 1541 had type B2/C lesions (1832 lesions) and 985 had long coronary lesions (>20 mm, 1139 lesions). Among the overall population, device success was achieved in 98.2% of lesions. TLF occurred in 12 (0.7%) patients (0.3% cardiac death, 0.2% TV-MI, 0.2% CI-TLR) at 30 days and in 43 (2.3%) patients (0.8% cardiac death, 0.8% TV-MI, 0.8% CI-TLR) at 12 months follow-up. The rate of definite stent thrombosis was 0.3% in the overall population at 12 months. The incidence of TLF and stent thrombosis was 6.2% and 1% in the diabetic, 1.8% and none in bifurcation lesion, 2.5% and 0.3% in type B2/C lesion, and 2.7% and 0.3% in long coronary lesions (>20 mm) subgroups, respectively. at 12 months follow-up.ConclusionThe S-FLEX UK-II registry confirms the clinical safety and performance of the ultrathin Supraflex Cruz SES in an all-comer population with complex coronary artery disease, demonstrating low rates of TLF and stent thrombosis.Trial registration numberISRCTN39751665(https://doi.org/10.1186/ISRCTN39751665)
How do parents experience video triage when seeking care for their acute ill children? A qualitative study in a Danish out-of-hours primary care setting
Authors: Nebsbjerg Mette Amalie , Bomholt Katrine Bjørnshave , Christensen Morten Bondo , Huibers Linda , Assing Hvidt Elisabeth 
Published: October 2024

ObjectiveThe objective is to explore parents’ experiences with telephone contacts to out-of-hours primary care (OOH-PC) that include use of one-way video (video triage).DesignA qualitative interview study using Braun and Clarke’s thematic analysis approach.SettingOOH-PC in the Central Denmark Region.ParticipantsA convenience sampling strategy was used to include parents of young children (aged 1–5 years), who received video triage in OOH-PC: nine women and one man aged 31–42 years. Data were collected from 26 April to 23 May 2023.ResultsThree main themes were developed, each containing two subthemes:Theme 1. Video triage accelerates diagnostic clarity and prompt action, enhancing feeling of safety: Parents experienced that video triage provided faster diagnostic clarification than telephone triage. The visual assessment in video triage reduced uncertainties of describing symptoms and increased the parents’ feeling of safety.Theme 2. Video triage changed the communicative and relational behaviour: Parents found video triage impersonal as it focused on the physical examination. The conversation before activation of video was found important, as it established a feeling of trust and reassurance.Theme 3. Experiences of presence and involvement in video triage: Parents found their active involvement in video triage challenging, as it required divided attention and shared responsibility.ConclusionsOur study indicates the importance of paying attention to the changes in communication and consultation processes afforded by the implementation of one-way video triage. One-way video triage is experienced as a valuable tool for examination, yet it is also perceived to impair the building of trust in the patient–physician relationship.
Effectiveness of a supervised group-based walking program on physical, psychological and social outcomes among older adults: a randomised controlled trial protocol
Authors: Wong Ming Yu Claudia , Leung Ka Man , Thøgersen-Ntoumani Cecilie , Ou Kailing , Chung Pak Kwong 
Published: October 2024

IntroductionTo minimise adverse health events among older adults, physical activity (PA) is considered one of the most fundamental and effective forms of lifestyle. Therefore, an urgent effort to promote a physically active lifestyle among our older adults is needed, in which walking could be a better choice, especially for mass promotion. Besides, the types of PA interventions were also shown to affect their effectiveness on older adults’ psychosocial outcomes. Hence, the overall aim of the project is to examine the effectiveness of supervised group-based walking intervention by comparing it with unsupervised group-based walking and unsupervised individual-based walking interventions on improving physical, psychological and social outcomes among older adults in Hong Kong.Methods and analysisThe research will conduct a four-group (supervised group-based, unsupervised group-based walking, unsupervised individual-based, control group), double-blind, randomised control trial, targeting 184 older adults in Hong Kong. The primary outcomes will be measured by participants’ changes in resting heart rates, body compositions, resting blood pressures, walking performance, loneliness, perceived social support and PA enjoyment. The results will be analysed using repeated analysis of variance and one-way analysis of covariance, as well as by conducting in-depth interviews with selected participants. Also, the outcomes of the research will be used as references for designing an effective walking operation manual for promoting healthy ageing among older adults in the community.Ethics and disseminationThe current study involves human participants, and the research protocol has been approved by the research ethics committee at Hong Kong Baptist University (Ref: R2022-2023-0013). All participants will be provided with written informed consent to participate. The outcomes of the intervention protocol will be disseminated through manuscript publications.Trial registration numberThe trial is registered at the ClinicalTrials.gov PRS (Trial ID:NCT05907252; date of first posted: 16 June 2023).
Rationale and design of Dapagliflozin vErsus SacubiTrIl-valsartaN therapY in Heart Failure with reduced ejection fraction (DESTINY-HF): a pragmatic randomised controlled trial protocol
Authors: Tiwari Krishna , Deora Surender , Choudhary Rahul , Kaushik Atul , Dwivedi Pradeep , Singh Surjit , Ambwani Sneha , Midha Naresh , Shukla Ravindra , Sankanagoudar Shrimanjunath , Shamim Muhammad Aaqib , Tiwari Vikas Kumar , Yadav Isha , Dodiya Rakesh , Varthya Shoban Babu 
Published: October 2024

Background
Heart failure affects almost 64 million people, with more than half of it constituting heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) are in the first line for HFrEF, but no head-to-head trials are available. Moreover, growth differentiation factor-15 (GDF-15) has been demonstrated as a promising prognostic marker, specifically for HFrEF, but has not been explored much.

Methods
This pragmatic randomised controlled trial recruits 100 patients with HFrEF (ejection fraction &40%) of New York Heart Association (NYHA) II–III and allocates them in a 1:1 ratio to the dapagliflozin and sacubitril/valsartan groups. The primary objective is to assess the difference in N-terminal pro-brain natriuretic peptide serum levels at the end of 16 weeks. The secondary efficacy objectives are to assess GDF-15, Kansas City Cardiomyopathy Questionnaire-overall summary score and estimated glomerular filtration rate. Patients will be assessed at baseline, fourth week and 16th week after randomisation. As health technology assessment practices widely differ in countries, cost assessment is a vital factor to consider. The cost needed to treat one cardiovascular event is also compared between both groups. The occurrence of safety events will also be evaluated at each follow-up point.

Conclusion
This pragmatic study aims to compare the efficacy, safety and cost-effectiveness of dapagliflozin versus sacubitril/valsartan in patients with HFrEF in real-world settings. The study aims to provide clinicians with data to make informed decisions regarding the preferred drug class. Additionally, examining the impact of ARNI and SGLT2i on GDF-15 levels could offer better insights into prognosis among patients with HFrEF.

Ethics and dissemination
This study involves human participants and was approved by Institutional Ethics Committee at AlIMS Jodhpur with reference number AIIMS/IEC/2023/5842 approved this study. Participants gave informed consent to participate in the study before taking part. The research findings will be disseminated via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts, and social media.

Trial registration number
CTRI/2023/12/060772.
Anticoagulation Therapy Timing in patients with Atrial Fibrillation after Acute and Chronic Subdural Haematoma (ATTAACH): a pilot randomised controlled trial
Authors: Mansouri Alireza , Nassiri Farshad , Scales Damon , Pirouzmand Farhad 
Published: October 2024

IntroductionSubdural haematomas (SDHs), acute or chronic, are common neurosurgical diagnoses. These problems can occur among patients requiring direct oral anticoagulation (DOAC) for atrial fibrillation. There are currently no guidelines regarding the optimal timing to resume anticoagulation for these patients after SDH. The objective of this study is to evaluate the feasibility of conducting a future large randomised controlled trial (RCT) evaluating the safety and efficacy of resuming DOACs early (ie, at 30 days) vs late (ie, at 3 months) for patients with atrial fibrillation following diagnosis of SDH.Methods and analysisThis is a pilot, open-label, multicentre RCT that will enrol adults with newly diagnosed acute or chronic SDH with or without other intracranial bleeding who were receiving therapeutic anticoagulation with a DOAC as stroke prophylaxis for atrial fibrillation. Patients will be randomly allocated to resume a DOAC at standard dosing starting either days 30+7 or days 90±14. The primary outcomes for the pilot RCT are recruitment rate, protocol adherence and patient compliance with the randomly allocated interventions. Secondary outcomes are patient functional outcomes and safety and effectiveness outcomes, which will comprise key endpoints for the future planned RCT. This pilot RCT will provide important data to inform the feasibility of conducting a future, large RCT of early versus late resumption of DOACs for atrial fibrillation stroke prophylaxis in patients newly diagnosed with SDH. The future RCT will help inform management of a commonly encountered clinical dilemma with high associated morbidity and mortality.Ethics and disseminationThis study has been approved by the research ethics board of record. It will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. Informed consent will be obtained from eligible patients or substitute decision-makers. Data from this study will inform the design of future, larger RCTs.Trial registration numberNCT05472766.
Integrated cervical cancer screening uptake and associated factors among women attending primary care services at public health centres in Addis Ababa, Ethiopia: a multicentre cross-sectional study
Authors: Kassa Rahel Nega , Gelaye Kassahun Alemu , Omigbodun Akinyinka 
Published: October 2024

BackgroundCervical cancer (CC) is a major health problem in Ethiopia. Integrated healthcare approaches have been suggested as a way to increase access to and utilisation of screening services. Limited data exists on integrated CC screening (CCS) uptake at the primary care facilities where most women access healthcare. This study aimed to determine integrated CCS uptake and associated factors among women attending primary care services at health centres (HCs) in Addis Ababa, Ethiopia.MethodsA multicentred cross-sectional study design was conducted among 1366 women attending primary care services at HCs in Addis Ababa. A systematic random sampling method was used to reach the study participants. Sexually active women aged 30–49 years attending primary care services in HCs were included in the study. A multivariable logistic regression model, with Stata/MP V.17.0 software, was used to identify the factors associated with integrated CCS service utilisation at a p value<0.05. Findings were presented using adjusted OR (AORs) with 95% CI.ResultOnly 15.6% (95% CI: 13.7 to 17.6) of women used the CCS that was integrated into the primary care services that they initially sought. Being single (AOR: 4.10; 95% CI: 2.19 to 7.68), divorced (AOR: 2.33; 95% CI: 1.04 to 5.21), attending college and above (AOR: 5.86; 95% CI: 2.32 to 14.79), being in the richest wealth index (AOR: 2.76; 95% CI: 1.46 to 5.22), husband’s sexual behaviour (AOR: 6.8; 95% CI: 4.09 to 11.21), having a favourable attitude towards CCS (AOR: 2.24; 95% CI: 1.52 to 3.29) and visiting postnatal clinic (AOR: 8.06; 95% CI: 2.33 to 27.8) were associated with utilisation of CCS services, while preference of a specific gender of healthcare provider (HCP) (AOR: 0.04; 95% CI: 0.02 to 0.13) was associated with non-utilisation of CCS.ConclusionThe study found low integrated CCS uptake among women in Addis Ababa, influenced by factors like marital status, education, wealth, husband’s sexual behaviour, attitude towards CCS, postnatal clinic visits and preferred gender of HCPs. Taking these factors into consideration by stakeholders could promote CCS utilisation.
Intraoperative contrast-enhanced cone beam CT allows visualization of the ‘dark side’ of the clot and improves mechanical thrombectomy performance
Authors: Hofmeister Jeremy , Rosi Andrea , Bernava Gianmarco , Reymond Philippe , Brina Olivier , Yilmaz Hasan , Carrera Emmanuel , Lovblad Karl-Olof , Machi Paolo 
Published: October 2024

BackgroundVisualization of the clot is key to the endovascular treatment of ischemic stroke, but identification of the distal part of the clot and distal arteries during mechanical thrombectomy (MT) remains challenging with conventional intraoperative imaging. We aimed to leverage the potential of contrast-enhanced cone beam CT (CE-CBCT) to better visualize the distality (‘dark side’) of the clot.MethodsWe retrospectively analyzed all patients treated with MT for medium vessel occlusion (MeVO) guided by three-dimensional (3D) imaging to identify those who underwent either CE-CBCT or 3D rotational angiography (3DRA). Our primary outcome was the visualization of the proximal and distal edges of the clot and the arteries beyond the occlusion on the different types of intraoperative imaging: digital subtraction angiography (DSA), 3DRA, and CE-CBCT. Secondary outcomes included the efficacy, safety, and timing of MT between CE-CBCT versus 3DRA groups.ResultsThe proximal edge of the clot was well visualized by DSA, 3DRA, and CE-CBCT. However, the distal edge of the clot and distal arteries were significantly better visualized with CE-CBCT (60.0%) than 3DRA (2.7%) and DSA (11.4–13.5%). Moreover, MT efficacy was better with CE-CBCT than 3DRA, with higher first-pass effect (65.7% vs 37.8%) and final recanalization grade (expanded Treatment In Cerebral Infarction (eTICI) 3: 71.4% vs 43.2%). Finally, the visualization of the distal edge of the clot and distal arteries correlated with better collateralization grade.ConclusionCE-CBCT localizes the clot and reveals the underlying vascular anatomy better than 3DRA or DSA, thereby enhancing the efficacy of MT. The improved filling of collaterals with CE-CBCT may explain this better visualization of the ‘dark side’ of the clot.