bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7
Authors: Bellon Marcia , Yeh Chien-hung , Bai Xue Tao , Nicot Christophe 
Published: June 2024

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL). Mutational analysis has demonstrated that the tumor suppressor, F-box and WD repeat domain containing 7 (FBXW7/FBW7/CDC4), is mutated in primary ATL patients. However, even in the absence of genetic mutations, FBXW7 substrates are stabilized in ATL cells, suggesting additional mechanisms can prevent FBXW7 functions. Here, we report that the viral oncoprotein Tax represses FBXW7 activity, resulting in the stabilization of activated Notch intracellular domain, c-MYC, Cyclin E, and myeloid cell leukemia sequence 1 (BCL2-related) (Mcl-1). Mechanistically, we demonstrate that Tax directly binds to FBXW7 in the nucleus, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 substrates. In support of the nuclear role of Tax, a non-degradable form of the nuclear factor kappa B subunit 2 (NFκB2/p100) was found to delocalize Tax to the cytoplasm, thereby preventing Tax interactions with FBXW7 and Tax-mediated inhibition of FBXW7. Finally, we characterize a Tax mutant that is unable to interact with FBXW7, unable to block FBXW7 tumor suppressor functions, and unable to effectively transform fibroblasts. These results demonstrate that HTLV-I Tax can inhibit FBXW7 functions without genetic mutations to promote an oncogenic state. These results suggest that Tax-mediated inhibition of FBXW7 is likely critical during the early stages of the cellular transformation process.

IMPORTANCE
F-box and WD repeat domain containing 7 (FBXW7), a critical tumor suppressor of human cancers, is frequently mutated or epigenetically suppressed. Loss of FBXW7 functions is associated with stabilization and increased expression of oncogenic factors such as Cyclin E, c-Myc, Mcl-1, mTOR, Jun, and Notch. In this study, we demonstrate that the human retrovirus human T-cell leukemia virus type 1 oncoprotein Tax directly interacts with FBXW7, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 cellular substrates. We further demonstrate that a Tax mutant unable to interact with and inactivate FBXW7 loses its ability to transform primary fibroblasts. Collectively, our results describe a novel mechanism used by a human tumor virus to promote cellular transformation.
Higher genotypic diversity and distinct assembly mechanism of free-living Symbiodiniaceae assemblages than sympatric coral-endosymbiotic assemblages in a tropical coral reef
Authors: Lin Sitong , Li Ling , Zhou Zhi , Yuan Huatao , Saad Osama S. , Tang Jia , Cai Wenqi , Yu Kefu , Lin Senjie 
Published: June 2024

ABSTRACT

While
in hospite
Symbiodiniaceae dinoflagellates are essential for coral health, ambient free-living counterparts are crucial for coral recruitment and resilience. Comparing free-living and
in hospite
Symbiodiniaceae communities can potentially provide insights into endosymbiont acquisition and recurrent recruitment in bleaching recovery. In this study, we studied coral-endosymbiotic and ambient free-living Symbiodiniaceae communities in the South China Sea. We collected samples from 183 coral and ambient plankton samples and conducted metabarcoding to investigate the diversity distribution, driving factors, and assembly mechanisms of the two groups of Symbiodiniaceae. Results revealed
Cladocopium
C1 and
Durusdinium
D1 as dominant genotypes. We detected a higher genotypic diversity in free-living than
in hospite
symbiodiniacean communities, but with shared dominant genotypes. This indicates a genetically diverse pool of Symbiodiniaceae available for recruitment by corals. Strikingly, we found that the cooler area had more Symbiodiniaceae thermosensitive genotypes, whereas the warmer area had more Symbiodiniaceae thermotolerant genotypes. Furthermore,
in hospite
and free-living Symbiodiniaceae communities were similarly affected by environmental factors, but shaped by different assembly mechanisms. The
in hospite
communities were controlled mainly by deterministic processes, whereas the ambient communities by stochastic processes. This study sheds light on the genetic diversity of source environmental Symbiodiniaceae and differential assembly mechanisms influencing Symbiodiniaceae inside and outside corals.

IMPORTANCE

Symbiodiniaceae dinoflagellates play a pivotal role as key primary producers within coral reef ecosystems. Coral-endosymbiotic Symbiodiniaceae communities have been extensively studied, but relatively little work has been reported on the free-living Symbiodiniaceae community. Conducting a comparative analysis between sympatric coral-endosymbiotic and free-living Symbiodiniaceae communities can potentially enhance the understanding of how endosymbiont communities change in response to changing environments and the mechanisms driving these changes. Our findings shed light on the genetic diversity of source environmental Symbiodiniaceae and differential assembly mechanisms shaping free-living and
in hospite
Symbiodiniaceae communities, with implications in evaluating the adaptive and resilient capacity of corals in response to future climate change.
Neutrophil-to-lymphocyte ratio as a biomarker of acute pulmonary exacerbations in children with cystic fibrosis: a retrospective cohort study
Authors: Tung Nicole Wing Hei , Edmondson Claire , Westrupp Nicole , Rosenthal Mark , Davies Jane C 
Published: June 2024

BackgroundNeutrophils are key contributors to chronic airway inflammation in cystic fibrosis (CF) lung disease, although airway and blood-based neutrophil markers are seldom used. The neutrophil-to-lymphocyte ratio (NLR) is an accessible biomarker, the clinical utility of which has not been adequately studied.ObjectiveThis study aimed to investigate the characteristics of the NLR in children with CF and its correlations with acute pulmonary exacerbations and spirometry.DesignA previous study had collected clinical data from children with CF for a 3-year period between 2016 and 2021. Retrospectively, NLR values were categorised according to patients’ clinical status during blood sample collection as ‘stable’, ‘acute pulmonary exacerbation’ or ‘elective admission for chronic clinical concern’.Main outcome measuresDemographic characteristics associated with the NLR; changes in NLR values in relation to clinical status; relationship between NLR and lung function.Results141 children with CF were included. NLR values during clinical stability were higher in females and increased with age. For children admitted for intravenous antibiotics, NLR values significantly increased from clinical stability (median (IQR)=1.13 (0.75–1.51)) to acute pulmonary exacerbations (median (IQR)=1.50 (0.96–2.65), p=0.001), but similar changes were not observed in elective admissions. The NLR was not associated with lung function.ConclusionsThe NLR demonstrated associations with clinical status in children with CF with significant elevations during acute pulmonary exacerbations. While its utility as a single-marker measure is limited, monitoring the NLR over time may help identify periods of increased inflammation.
Lessons learnt from daily oral PrEP delivery to inform national planning for PrEP ring introduction for women in low-income and middle-income countries: a qualitative inquiry of international stakeholders
Authors: Heck Craig J , Dam Anita , Yohannes Kibret , Deacon Justine , Kripke Katharine , Meyers Kathrine , Poku Ohemaa , Obermeyer Christopher , Wiant Sarah , Quigee Daniela , Larson Martha , Malati Christine , Sobieszczyk Magdalena E , Torres-Rueda Sergio , Castor Delivette 
Published: June 2024

IntroductionSome African countries plan to introduce and scale-up new long-acting pre-exposure prophylaxis methods (LA-PrEP), like the monthly dapivirine vaginal ring (PrEP ring) and injectable cabotegravir. National costed implementation plans, roadmaps for successful product implementation, are often overlooked. International stakeholders engaged in oral PrEP planning, introduction and scale-up are an information resource of lessons learned to advise LA-PrEP planning. We consulted such international stakeholders and synthesised oral PrEP lessons to inform the development of a costed rollout plan template for LA-PrEP.MethodsFrom selected global health organisations (five international nongovernmental, four donor, four university/research and two multilateral), we interviewed 27 representatives based in America, Europe, Asia and Africa about strategic content and approaches for LA-PrEP policy, programming and implementation. We conducted a thematic analysis of the interview data for implementation considerations.ResultsFrom the consultations, we identified six implementation themes for LA-PrEP introduction and scale-up: (1) ethically increasing choice and avoiding coercion; (2) de-stigmatising PrEP by focusing on preference rather than risk-based eligibility; (3) integrating LA-PrEP into services that are more woman-oriented, couple-oriented and family-oriented, and providing private spaces for LA-PrEP delivery; (4) de-medicalising delivery of relatively safe products (eg, PrEP ring); (5) constructing multilevel, nuanced communication strategies to address measured and perceived product efficacy and effectiveness; and (6) devising product-agnostic, modular approaches to service delivery. Despite the widespread emphasis on integration, few stakeholders offered empirical examples of successful integration approaches and frameworks.ConclusionsLessons learnt from stakeholder participants suggest standardised and modular processes can improve efficiencies in LA-PrEP planning and implementation. Tiered communication strategies addressing product efficacy and effectiveness will improve clients’ and providers’ efficacy in making informed decisions. Integration is important for LA-PrEP delivery, but data on empirical integration approaches and frameworks is minimal: further research in this discipline is needed.
Breaking barriers: assessing the impact of clinical quality improvements on reducing health disparities in hypertension care among Mumbai’s urban slums
Authors: Li Shang Ju , Miles Thomas , Vasisht Itisha , Dere Harshwardhan , Agyekum Celestina , Massoud Rashad 
Published: June 2024

The clinical quality improvement initiatives, led by the organisation’s Health Equity Working Group (HEWG), aim to support healthcare providers to provide equitable, quality hypertension care worldwide. After coordinating with the India team, we started monitoring the deidentified patient data collected through electronic health records between January and May 2021. After stratifying data by age, sex and residence location, the team found an average of 55.94% of our hypertensive patients control their blood pressure, with an inequity of 11.91% between male and female patients.The objective of this study was to assess the effectiveness of using clinical quality improvement to improve hypertension care in the limited-resourced, mobile healthcare setting in Mumbai slums. We used the model for improvement, developed by Associates in Process Improvement. After 9-month Plan-Do-Study-Act (PDSA) cycles, the average hypertensive patients with controlled blood pressure improved from 55.94% to 89.86% at the endpoint of the initiative. The gender gap reduced significantly from 11.91% to 2.19%. We continued to monitor the blood pressure and found that the average hypertensive patients with controlled blood pressure remained stable at 89.23% and the gender gap slightly increased to 3.14%. Hypertensive patients have 6.43 times higher chance of having controlled blood pressure compared with the preintervention after the 9-month intervention (p<0.001).This paper discusses the efforts to improve hypertension care and reduce health inequities in Mumbai’s urban slums. We highlighted the methods used to identify and bridge health inequity gaps and the testing of PDSA cycles to improve care quality and reduce disparities. Our findings have shown that clinical quality improvement initiatives and the PDSA cycle can successfully improve health outcomes and decrease gender disparity in the limited-resource setting.
Using systems mapping within the process evaluation of a randomised controlled trial of the ACE active ageing programme in England and Wales
Authors: Cavill Nick , Greaves Colin , Chatwin Katie E , Szekeres Zsofia , Davies Amy , Hawley-Hague Helen , Crone Diane , Withall Janet , Thompson Janice , Stathi Afroditi 
Published: June 2024

BackgroundSystem mapping has mainly been used to develop theories and understanding of complex systems; to hypothesise how an intervention might work in a complex system or to inform intervention development. There are a few examples of the use of system mapping as part of process evaluation. In this paper, we describe an innovative approach to using system mapping as part of the process evaluation of a randomised controlled trial of the Active, Connected, Engaged (ACE) community-based active ageing programme.MethodTen participatory workshops were held across three of the ACE sites (Cardiff, Stoke-on-Trent and Manchester, UK). These involved over 100 participants, volunteers and stakeholders (from National Health Service, statutory and voluntary sectors). Their aim was to gather area-specific information on participants’ barriers and facilitators to physical activity and the needs of peer volunteers and service providers; and create ‘baseline’ system maps before the launch of the programme in the three areas of ACE delivery.ResultsSystem maps were produced showing the main outcome (physical activity) and the interactions between the key motivators and barriers described by older people, as well as ideas from stakeholders and volunteers about how these barriers can be addressed. Findings led to refinements to ACE intervention processes and the study’s logic model.ConclusionsSystem mapping helped to refine the ACE processes and fine-tune the logic model. The value of this approach will increase in the next phase when it will be used to explore any changes to the physical activity system including changes to stakeholders’ ways of working and collaborating to tackle barriers to activity following the completion of the ACE trial.Trial registration numberISRCTN17660493.
Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions: a systematic review and meta-analysis
Authors: Ahmed Syed Hassan , Zakai Aabia , Zahid Maha , Jawad Muhammad Youshay , Fu Rui , Chaiton Michael 
Published: June 2024

BackgroundGlobally, populations afflicted by armed conflict are known to have high rates of mental health disorders.AimsThis meta-analysis aims to estimate the prevalence of post-traumatic stress disorder (PTSD) and depressive symptoms among civilians residing in armed conflict-affected regions.MethodsThis meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A literature search employing MEDLINE(R), Embase Classic+Embase, APA PsycINFO, Ovid Healthstar, Journal@Ovid Full Text, Cochrane, PTSDpubs and CINAHL was conducted from inception until 19 March 2024 to identify relevant studies. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies, and a Comprehensive Meta-Analysis was used to conduct the statistical analysis.ResultsThe search yielded 38 595 articles, of which 57 were considered eligible for inclusion. The included studies comprised data from 64 596 participants. We estimated a prevalence of 23.70% (95% CI 19.50% to 28.40%) for PTSD symptoms and 25.60% (95% CI 20.70% to 31.10%) for depressive features among war-afflicted civilians. The subgroup analysis based on time since the war and the country’s economic status revealed the highest prevalence for both PTSD and depressive symptoms was present during the years of war and in low/middle-income countries.ConclusionsThe results of this study provide conclusive evidence of the detrimental impacts of armed conflict on mental health outcomes. Hence, it is crucial to emphasise the significance of both physical and mental health in the aftermath of war and take appropriate humanistic measures to overcome challenges in the management of psychiatric illnesses.PROSPERO registration numberCRD42023416096.
Efficacy and safety of ultrasound-guided versus landmark-guided neuraxial puncture: a systematic review, network meta-analysis and trial sequential analysis of randomized clinical trials
Authors: de Carvalho Clístenes Crístian , Porto Genuino Willgney , Vieira Morais Maria Clara , de Paiva Oliveira Heleno , Rodrigues Adolfo Igor , El-Boghdadly Kariem 
Published: June 2024

BackgroundData suggest that preprocedural ultrasound may improve the efficacy of central neuraxial puncture. However, it remains uncertain whether these findings can be extended to various clinical scenarios, including diverse patient populations and the application of real-time ultrasound guidance. Additionally, it is unclear whether ultrasound-guided techniques improve safety and patient-centered outcomes.MethodsWe searched six databases for randomized trials of adult patients undergoing neuraxial puncture, comparing real-time ultrasound, preprocedural ultrasound, and landmark palpation for efficacy, safety and patient-centered outcomes. Our primary outcome was a failed first-attempt neuraxial puncture. After two-person screening and data extraction, meta-analyses were conducted and the Grading of Recommendations Assessment, Development and Evaluation approach was applied to assess the certainty of evidence.ResultsAnalysis of 71 studies involving 7153 patients, both real-time ultrasound (OR 0.30; 95% credible interval (CrI) 0.15 to 0.58; low certainty) and preprocedural ultrasound (OR 0.33; 95% CrI 0.24 to 0.44; moderate certainty) showed a significant reduction in the risk of a failed first neuraxial puncture. Real-time ultrasound had the best performance for preventing first-attempt failures (low certainty evidence). Although real-time ultrasound was also the leading method for reducing the risk of complete neuraxial puncture failure, the results did not show a statistically significant difference when compared with landmark palpation. Preprocedural ultrasound, however, significantly reduced the odds of complete puncture failure (OR 0.29; 95% CrI 0.11 to 0.61). These ultrasound-guided approaches also contributed to a reduction in certain complications and increased patient satisfaction without any other significant differences in additional outcomes. Trial sequential analysis confirmed that sufficient information was achieved for our primary outcome.ConclusionsUltrasound-guided neuraxial puncture improves efficacy, reduces puncture attempts and needle redirections, reduces complication risks, and increases patient satisfaction, with low to moderate certainty of evidence. Despite real-time ultrasound’s high ranking, a clear superiority over preprocedural ultrasound is not established. These results could prompt anesthesiologists and other clinicians to reassess their neuraxial puncture techniques.
Clinical implications of haemodynamics in symptomatic intracranial atherosclerotic stenosis by computational fluid dynamics modelling: a systematic review
Authors: Liu Yu , Li Shuang , Liu Haipeng , Tian Xuan , Liu Yuying , Li Ziqi , Leung Thomas W , Leng Xinyi 
Published: June 2024

BackgroundRecently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically reviewed in this study.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements, we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.Results19 articles met the inclusion criteria, all studies recruiting patients from China. Most studies used CT angiography (CTA) as the source image for vessel segmentation, and generic boundary conditions, rigid vessel wall and Newtonian fluid assumptions for CFD modelling, in patients with 50%-99% sICAS. Pressure and wall shear stress (WSS) were quantified in almost all studies, and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio (PR) and stenotic-throat to prestenotic WSS ratio (WSSR). Lower PR was associated with more severe stenosis, better leptomeningeal collaterals, prolonged perfusion time and internal borderzone infarcts. Higher WSSR and other WSS measures were associated with positive vessel wall remodelling, regression of luminal stenosis and artery-to-artery embolism. Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease. Moreover, translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy, which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.ConclusionsCFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS. Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS, for its wider applications in clinical research and practice.
Merits of atomic cascade computations
Authors: Fritzsche S. , Sahoo A. K. , Sharma L. , Wu Z. W. , Schippers S. 
Published: June 2024

Abstract
Atomic cascades refer—first and foremost—to the stepwise de-excitation of excited atoms owing to the emission of electrons or photons. Apart from dedicated experiments at storage rings and synchrotrons, such cascades frequently occur in astro and plasma physics, material research, surface science and at various places elsewhere. In addition, moreover, “atomic cascades” have been found a useful concept for modeling atomic behavior under different conditions, for instance, when dealing with the photoabsorption of matter, the generation of synthesized spectra, or for determining a rather wide class of (plasma) rate coefficients. We here compile and discuss several atomic cascades (schemes) that help predict cross sections, rate coefficients, electron and photon spectra, or ion distributions. We also demonstrate how readily these schemes have been implemented within JAC, the Jena Atomic Calculator. Emphasis is placed on the classification of atomic cascades and their (quite) natural breakdown into cascade computations, to deal with the electronic structure and transition amplitudes of atoms and ions, as well as the cascade simulation of those properties and spectra, that are experimentally accessible. As an example, we show and discuss the computation of dielectronic recombination plasma rate coefficients for beryllium-like gold ions. The concept of atomic cascades and its implementation into JAC can be applied for most ions across the periodic table and will facilitate the modeling and interpretation of many forthcoming observations.

Graphical abstract