bluuebunny/crossref_metadata_2025 huggingface dataset:
N42 New tool for IBD nurses to support IBD patients
Authors: Toivonen T T I , Perttula K , Oksanen S , Ilus T , Mattila M
Published: January 2024

Background

There are about 58000 Inflammatory Bowel Disease (IBD) patients in Finland. The number has doubled in ten years. Over 5500 IBD patients live in the Pirkanmaa region. Patients are treated in three different hospitals and there are eight trained IBD nurses in adult services. Patients can contact a call back-system at any hour of the day. With growing number of patient contacts there is a need for additional contact channels and ways of support for patients care.

Methods

TaysPolku is an app developed by Buddy HealthCare where IBD patients can see their appointments, upcoming procedures, information packages, medication instructions, videos and questionnaires related to their treatment all in one place. TaysPolku provides automatic reminders and enables them to contact their own care unit directly via message. IBD nurses has been part of creating material for TaysPolku. IBD nurse explains the app and creates TaysPolku for the patient after providing the necessary information. The app is downloaded from app stores, verified by strong authentication. The app works with any face ID or pin number chosen by the patient.

Results

TaysPolku was introduced in June 2021 and the first users were patients receiving intravenous biologicals. IBD nurses informed about the new service during the infusion visits and provided written material. In the next phase, TaysPolku was set up for biological self-injecting patients. Currently, TaysPolku have been created 299 patients at Tampere University Hospital Tays. The utilization rate of the created TaysPolku is high. Messages on TaysPolku has been send/received 3896 times. The messages feature enables the care unit to reach everyone using TaysPolku simultaneously. It is used in all three hospitals and every IBD nurses take care of it. Satisfaction with TaysPolku has been good for both patients and IBD nurses. Patient questionnaire highlighted the benefits, and the answers highlighted the ease of use of the service.

"A well-functioning system "

"Reminds me very much of the lab, questions and treatment days. Easy to useand connect. There could also be a connection to other departments when care is taken in other departments as well"

Conclusion

Different forms of service are needed with the growing number of patients, and a digital app that supports the patient's self-care has been proven to work. Further development is underway to offer a similar service to all IBD patients in the region.
N43 The East Kent experience of switching from intravenous infliximab to subcutaneous, benefits to the patients, the service and financial implications
Authors: Abreu B , Scott G
Published: January 2024

Background

This project started due to two main problematics, Medical Day Unit (MDU) capacity and costs savings. Infliximab is used to treat IBD, and is initially administered by infusion, arranged by MDU. Due to increased need of biologics, MDU capacity decreased and patients waited a minimum of 6 weeks for first treatment, which can cause flares and, consequently, need steroids or attendance to A&E. If patients were able to self-administer treatment, they would not need to attend MDU and those appointments could be used for new patients. Treatment costs savings have positive financial implications to the Trust. Another benefit is that patients have more independence and do not have to attend MDU for their infusions.

Methods

To organize this, we had regular meetings with our Homecare Pharmacy team so we could understand the implications to our service, Homecare availability for the increase of prescriptions and homecare company for stock requirements and availability of a nurse visit.

Once all processes were clear, we visited MDU frequently for face-to-face discussion with patients at their appointment. During these conversations, we demonstrated what supplies the patient will receive and explained with demonstration pens. We noted that patients feel more reassured if they can be familiar with the injections and raise any concerns. During the days we could not attend MDU, we arranged letters for the patients, and had positive feedback as they contacted our helpline showing interest to switch. Another strategy is to discuss this process before starting treatment, so patients can have everything arranged while having their loading doses.

Results

Before organising this, we had 14 patients on infliximab subcutaneous injections. From April 2023 to 16/11/23 we have switched 58.4% of patients. Potential cost saving to the trust includes no VAT payment on homecare products, no nursing time cost, medical devices and disposable cost and MDU cost. From patient feedback it is shown that patients prefer subcutaneous injections as this reduces the time spent in MDU, cost of travel and better symptom control. This is work in progress and we will have further information on successes at the year end.

Conclusion

Our goal was to switch 40% of infliximab by the third quadrimester and have switched 58.4%. This is an ongoing process, patients are started on infliximab regularly so need to ensure they are aware of this option. This project has been very successful for both patients and the Trust. We only switched back 3 patients due to side effects and flares. We will continue with this initiative so we can promote patient independence, decrease waiting times for loading doses and to improve cost savings to the Trust.
N47 Spiritual needs of patients with IBD: preliminary results of a pilot study
Authors: Starnella G , Rosato I , Canova C , Savarino E V , Zingone F , Barberio B , Lorenzon G , Gregori D , Comoretto R I , Martinato M
Published: January 2024

Background

Inflammatory bowel disease (IBD) includes Crohn's Disease (CD) and Ulcerative Colitis (UC), and both lead to manifestations that affect the patient's quality of life (QoL). The issue of chronicitỳ makes the disease difficult to manage and requires a radical change in patients’ habits, leading to a decrease in QoL after diagnosis. The literature emphasises how spiritualitỳ positively influences the psychophysical well-being of chronic patients and consequently their QoL.

This study aims to describe the spiritual needs of patients with IBD to promote holistic care and improve their QoL and aims to explore their eventual association with sociodemographic and clinical variables.

Methods

A cross-sectional study was carried out in the outpatient gastroenterology clinics of a university hospital, administering the validated Spiritual Needs Questionnaire (SpNQ) during outpatient follow-up visits to patients over 18 years of age after informed consent to participate in the study. The SpNQ consist of 27 items divided into four domains: Religious needs, Needs for Inner Peace, Existential needs, and Giving/Generativity Needs. Some clinical and sociodemographic data were also collected.

Results

A total of 103 completed the questionnaire: 53% had CD, 35% UC and 12% had undetermined IBD. 44% were males the median age was 45 years, and half of the sample was more than 10 years from IBD diagnosis. More than 40% were in biologics, 47% had a high educational level, 28% were smokers, and 4% had a stoma. 65% were Christian, 26% had no religion, and the frequency of their participation in religious gatherings varies from never (15%), to rarely (59%) and often (26%).

They cultivate their spirituality mainly by conducting their existence in accordance with values that are fundamental to them (47.7%), staying in contact with nature (30.5%), praying (15.8%), engaging in introspection and self-knowledge (14.7%), volunteering (12.6%), and practising extreme sports (10.5%).

The analyses showed statistically significant differences between sexes regarding the domains "Needs for Inner Peace" and "Religious Needs" (p<0.001) more relevant to women than men, and significant differences between ages regarding the domains "Existential Needs", more relevant to middle age (p=0.037), and "Giving/Generativity Needs", more relevant to middle age and to elderly (p=0.015).

Conclusion

Spiritual needs may play a major role in the care of patients with IBD, and nursing should consider this dimension to improve the holistic care of the patients. Research should be expanded through studies involving a larger sample size and evaluating the IBD outcome by acting on spiritual needs.
N48 Exploring & evaluating the benefits of initiating an IBD Transition clinic
Authors: Scott G
Published: January 2024

Background

Establishing an Inflammatory Bowel Disease (IBD) Transition Clinic can bring about several significant benefits. This includes providing continuity of care, specialised care, education in new treatment, emotional support, collaboration and coordination of care, empowering patients and assisting in adherence to medication and follow up appointments. In the author's history within the Trust there has never been an established IBD Transition clinic. This has led to young adults delayed in transitioning to adult services without any formal handover.

Methods

The IBD Consultant Nurse felt that the young adults were given a second class service and that they were not receiving the care and advice that they needed in the difficult time of being a young adult with a long term condition. They enlisted the help of a paediatric gastroenterologist and worked with the paediatric operations team and a cohort of patients were booked into a three monthly clinic held on a Saturday as this was felt the best day for engaging both patients and family. The paediatric gastroenterologist and IBD Consultant Nurse undertook the clinic jointly.

Results

A number of clinics were undertaken and the IBD Consultant Nurse asked for all patients to be assigned to an adult gastroenterologist after the first appointment. At the joint clinic all medication was discussed and a personalised plan of care was adopted for all patients to allow a smooth transition into adult services. The feedback from patients and family members was extremely favourable and all patients felt that they had been given all of the required information, a personalised care plan and were prepared to be transitioned to adult care. All patients were given a post clinic questionnaire on their satisfaction of the Transition clinic. The clinic was recently stopped as a adult gastroenterologist felt that this should not have been undertaken by a nurse and that they can only be undertaken by doctors. The current waiting time to be reviewed by a gastroenterologist is currently around 65weeks which could lead to a delay in treatment.

Conclusion

Ideally establishing a nurse-led transition clinic requires collaboration among healthcare providers, administrative support, and resources dedicated to its development. Additionally, an emphasis on patient and family involvement in the planning and execution stages can lead to a more patient-centric and successful transition program. This clinic was extremely successful but has had to stop as the gastroenterologists feel that only gastroenterologists can undertake transition clinics and should not be nurse led. Unfortunately this will lead to transition patients having an extended delay into adult services.
ECCO Fellowship Generation of an IBD single-cell multiome ATLAS for deeper understanding of IBD sub-phenotypes
Authors: Pibiri Paola , Anderson Carl
Published: January 2024

Background and Aims

Inflammatory Bowel Disease (IBD) is one of the most prevalent gastrointestinal diseases worldwide (1, 2, 3). Disabling symptoms affect the quality of life of IBD patients, and incurred disability and healthcare costs result in a high socio-economic burden (1, 4, 5). Despite new biologicals and small-molecule drugs, patients deal with high rates of non-response, requiring therapy switching without evidence-based guidance on optimal therapy choices for each specific disease condition.

Methods

In an effort to better understand the disease pathomechanisms underlying IBD, an essential role has been played by single-cell RNA sequencing (scRNAseq). Two scRNAseq studies, one in Crohn’s disease (CD) (Martin e.a., Cell 2019), and one in ulcerative colitis (UC) (Smillie e.a., Cell 2019), characterized the molecular and functional heterogeneity of phenotypically similar IBD cases, and gave us the first clues on the mechanism underlying non-response to anti-TNFa. However, the statistical power of these studies is limited due to their small cohort sizes (6, 7, 8). To acquire further insights into IBD, and to definitively establish the mechanism underlying anti-TNFa non-response without having to generate costly new single-cell experiments, we propose harmonizing smaller IBD scRNAseq studies and performing large-scale meta-analyses. Specifically, our goal is to start with meta-analyzing four IBD scRNAseq datasets (two CD, each ~100 ind, and two UC, each ~30 ind) and to perform a powerful meta-analysis. To easily add more datasets we will create a pipeline for integrating scRNAseq data.

Anticipated Impact

The large meta-analysis will allow us to get more insight into the mechanisms underlying disease subphenotypes, and to get insight into the effect of commonly used IBD therapies (anti-TNFa, thiopurines) on the gut mucosal composition and inflammatory pathways. The datasets and related results will be made publicly available through a single-cell IBD ATLAS web interface, fulfilling the need for an easily queryable large IBD scRNAseq dataset.
ECCO Grant Investigating the role of gut eukaryotic virome in contributing to colorectal cancer carcinogenesis
Authors: Facoetti A , Massimino L , Cagliani S , Spanò S , Nicolò S , Errico C , Parigi T L , Riva M , Anselmo A , Villa C , Palmieri O , Latiano A , Danese S , Ungaro F
Published: January 2024

Background and Aims

Eukaryotic-targeting viruses have recently attracted considerable interest in gastrointestinal diseases such as ulcerative colitis (UC) and colorectal cancer (CRC)1–3, the fourth leading cause of cancer death in the world4. UC and CRC share several factors influencing their etiogenesis, including intestinal dysbiosis2,5–7. Our group has recently published a work pinpointing a gut virome-associated Orthohepadnaviridae protein, namely Hepatitis B protein X (HBx) to correlate with UC pathogenesis and promote intestinal inflammation in mice by disrupting the epithelial barrier and shaping the gut mucosal immune environment, independently of the microbiota3. Moreover, we showed that HBx is able to induce DNA damagerelated processes and active biological processes related to the Wnt pathway3 known to be involved in colorectal carcinogenesis8. Our preliminary results raised the hypothesis that a specific virome-derived protein may fill the gap existing between intestinal inflammation and CRC onset by stimulating pro-inflammatory and/or pro-carcinogenic effects. To verify this hypothesis, we here propose to address the following Aims:

Aim 1. To evaluate the carcinogenic effects and phenotypes induced by HBx in vivo.

Aim 2. To unveil the molecular and cellular dynamics of HBx-induced effects in vitro.

Methods

Aim 1. Two mouse models of carcinogenesis will be used. The first will be the orthotopic model of CRC performed by injecting HBx-overexpressing Caco-2 cells in the rectal mucosa. The second will be performed by continuously challenging mice with the HBx protein directly into the rectal mucosa over 10 weeks. Tumor growth will be monitored over time and tumor samples will be characterized for histology and multidimensional flow cytometry analysis. Distal organs will also be analyzed to evaluate the extent of the metastasization.

Aim 2. 3D models of intestinal mucosa microenvironment will be set up with HBxoverexpressing epithelial cells cocultured with intestinal immune and stromal cells. Then cells will be analyzed by single-cell transcriptomics and RNA pseudotime.

Anticipated Impact

Our study proposes an unconventional understanding of CRC carcinogenesis, investigating whether and how a eukaryotic virome-associated protein promotes CRC and exploring gut virome-dependent cellular and molecular mechanisms during CRC carcinogenesis.
ECCO Grant Dissecting the role of S1PR1 modulator in the mucosal regeneration of Ulcerative Colitis
Authors: Rizzo Giulia , Vetrano Stefania
Published: January 2024

Background and Aims

Ozanimod, a potent sphingosine 1-phosphate (S1P) 1/5 receptor agonist, first approved for the treatment of adults with moderately to severely active UC in the USA and in the EU, has showed promising results in terms of both tolerability and efficacy reducing inflammatory processes and inducing disease remission. The selectivity of Ozanimod for S1PR1 is 27 times that for S1PR5. Therefore, is plausible that the beneficial effects of Ozanimod are mediated by S1PR1, which is constitutively expressed not only by immune cells, but also by epithelial, endothelial, and stromal cells. However, its function on non-immune cells has been neglected. Based on preliminary data demonstrating a faster recovery of mucosal damage in mice with a conditional deletion of S1PR1 in the epithelia and endothelia compartments, our hypothesis is that the inactivation of S1PR1 not only inhibits immune cell trafficking, but also promotes tissue repair. Based on this background, the main objectives will be to exploit the Ozanimod effects during the process of mucosa healing, and to investigate the molecular pathways activated by Ozanimod on epithelial and endothelial cells.

Methods

Pre-clinical validation of Ozanimod, in vivo model of UC in association with conditional knockout mice for S1PR1 on epithelial and endothelial cells, stimulation of primary endothelial cells from UC patients and human induced pluripotent stem cell-derived intestinal organoids (iHOs) will be used to address our aims. Transcriptomics, functional assay, immune characterization, WB validation will be performed.

Anticipated Impact

In short and medium term, we will improve the knowledge on the role of S1PR1 in the processes of mucosal healing and identify the molecular pathways involved in the response to the mucosal damage mediated by the ozanimod in non-immune cells. The results of this study may improve the treatment options for UC patients.
Left ventricular inferior wall congenital diverticula in athletes: a case series and review of the literature
Authors: Di Gioia Giuseppe , Buzzelli Lorenzo , Segreti Andrea
Published: January 2024

Background

Congenital left ventricular diverticula (LVDs) and aneurysms (LVAs) are rare, developmental, cardiac anomalies, which are often asymptomatic. Sometimes they can cause life-threatening complications like arrhythmias, syncope, embolic events, ventricular wall rupture, valvular regurgitation, congestive heart failure, and various symptoms. Diagnosis is usually made after exclusion of acquired causes, from cardiac or non-cardiac disorders. Specific guidelines for LVD/LVA management are not available and treatment options are guided by different case-by-case clinical presentation and possible complications.

Case summary

We present a series of two patients with occasional diagnosis of diverticula of the inferior basal left ventricular wall in the context of cardiological evaluations for competitive sport certificate. Symptoms were present at clinical evaluation only in Patient 1, together with electrocardiogram (ECG) abnormality. We performed transthoracic echocardiography as a first-line examination and secondly, we confirmed the diverticula by cardiac magnetic resonance. A maximal stress test and 24 h ECG Holter were also performed.

In our case, in light of the clinical-instrumental findings, periodic medical and echocardiographic follow-up without therapy was established, together with the resumption of sports activities.

Discussion

Nowadays, no specific recommendations exist in athletes and no studies are available on how regular sport practice can influence natural history of LVD/LVA. The current case series highlights the importance of risk stratification for cardiac events, of a multimodal imaging approach in diagnostic procedure and of a tailored treatment strategy.
A case report of complex congenital heart disease co-existing with hypertrophic cardiomyopathy
Authors: Veeratterapillay Kuldeepa , Coats Caroline J , Martin Ruairidh , Chaudhry Bill , Coats Louise
Published: January 2024

Background

Myocardial abnormalities are sometimes overlooked in congenital heart disease (CHD). The co-existence of hypertrophic cardiomyopathy is so uncommon that it is assumed to be a coincidence rather than an association.

Case summary

A 24-year-old gentleman, who was previously clinically well following a staged Fontan palliation for single-ventricle CHD, was transferred to our centre following an out-of-hospital cardiac arrest. He had return of spontaneous circulation after a period of cardiopulmonary resuscitation. Initial electrocardiogram showed sinus bradycardia. Computed tomography pulmonary angiography ruled out pulmonary embolism. Transthoracic echocardiography and cardiac magnetic resonance (CMR) demonstrated marked ventricular hypertrophy with no left ventricular outflow tract obstruction. Punctate areas of late gadolinium enhancement were noted in the basal septum, and T1 values were consistent with fibrosis. Cardiac catheterization demonstrated low Fontan pressures and normal coronaries. Ventricular tachycardia rapidly degenerating into ventricular fibrillation was induced during electrophysiological studies. Genetic testing demonstrated a pathogenic cardiac myosin-binding protein C variant consistent with co-existent hypertrophic cardiomyopathy. Bisoprolol was initiated and a subcutaneous implantable cardiac defibrillator implanted 4 weeks after his initial presentation. Two years on, he remains well with no therapies from his defibrillator. As well as Fontan surveillance, cascade testing, exercise prescription, and pre-conception counselling were addressed during follow-up.

Discussion

In CHD, ventricular hypertrophy may relate to congenital or acquired systemic outflow tract obstruction. Contemporary CMR techniques combined with genetic testing can be useful in differentiating between hypertrophy caused by congenital anomaly vs. concurrent cardiomyopathies. Multidisciplinary expertise is critical for accurate diagnosis and optimal care.
Single-access, non-contrast transcatheter aortic valve implantation, the ultimate minimalist approach: a case report
Authors: Diaz Nuila Mario E , Gupta Ashish , Alkhalil Mohammad
Published: January 2024

Background

Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with symptomatic severe aortic stenosis. Patients with previous renal transplant are considered as a high-risk cohort who may develop procedural complications related to vascular access and renal impairment post-TAVI.

Case summary

Herein, we report a case of an 88-year-old male who presented with progressive dyspnoea. His transthoracic echocardiogram revealed severe aortic stenosis with a peak gradient of 75 mmHg and impaired left ventricle systolic function (an estimated ejection fraction of 40%). He had a background of kidney transplant with progressive decline in renal function, requiring the formation of left arm arteriovenous fistula in preparation for future dialysis. He was successfully treated with TAVI using a single vascular access site without administering contrast media.

Discussion

Single-access, non-contrast TAVI is feasible when treating renal transplant patients with severe aortic stenosis and limited vascular access. The current minimalistic approach should be used only in highly selective patient cases.
Building bridges to peace: a quantitative evaluation of power-sharing agreements
Authors: Mueller Hannes , Rauh Christopher
Published: January 2024

Power-sharing agreements are used as a tool to reduce political violence in regions of conflict, but agreements are often followed by violence. This is due to the fact that such agreements are introduced during periods of political violence when a country is inside the conflict trap, which makes it difficult to distinguish the effect of the agreement from the political context that generates persistent political violence. In this study, we match pre-agreement conflict risk to estimate the effects of power-sharing agreements on violence using a difference-in-difference method. The results show that violence falls immediately after an agreement, with the effects strengthening over time. Comprehensive agreements tend to be particularly successful. We show that broader institutional changes that have their nucleus in the agreements are crucial elements explaining these large changes.
How to assess and treat right ventricular electromechanical dyssynchrony in post-repair tetralogy of Fallot: insights from imaging, invasive studies, and computational modelling
Authors: Ložek Miroslav , Kovanda Jan , Kubuš Peter , Vrbík Michal , Lhotská Lenka , Lumens Joost , Delhaas Tammo , Janoušek Jan
Published: January 2024

Background and Aims

Right bundle branch block (RBBB) and resulting right ventricular (RV) electromechanical discoordination are thought to play a role in the disease process of subpulmonary RV dysfunction that frequently occur post-repair tetralogy of Fallot (ToF). We sought to describe this disease entity, the role of pulmonary re-valvulation, and the potential added value of RV cardiac resynchronization therapy (RV-CRT).

Methods

Two patients with repaired ToF, complete RBBB, pulmonary regurgitation, and significantly decreased RV function underwent echocardiography, cardiac magnetic resonance, and an invasive study to evaluate the potential for RV-CRT as part of the management strategy. The data were used to personalize the CircAdapt model of the human heart and circulation. Resulting Digital Twins were analysed to quantify the relative effects of RV pressure and volume overload and to predict the effect of RV-CRT.

Results

Echocardiography showed components of a classic RV dyssynchrony pattern which could be reversed by RV-CRT during invasive study and resulted in acute improvement in RV systolic function. The Digital Twins confirmed a contribution of electromechanical RV dyssynchrony to RV dysfunction and suggested improvement of RV contraction efficiency after RV-CRT. The one patient who underwent successful permanent RV-CRT as part of the pulmonary re-valvulation procedure carried improvements that were in line with the predictions based on his Digital Twin.

Conclusion

An integrative diagnostic approach to RV dysfunction, including the construction of Digital Twins may help to identify candidates for RV-CRT as part of the lifetime management of ToF and similar congenital heart lesions.
Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster
Authors: Everman Elizabeth R , Macdonald Stuart J
Published: January 2024

Copper is one of a handful of biologically necessary heavy metals that is also a common environmental pollutant. Under normal conditions, copper ions are required for many key physiological processes. However, in excess, copper results in cell and tissue damage ranging in severity from temporary injury to permanent neurological damage. Because of its biological relevance, and because many conserved copper-responsive genes respond to nonessential heavy metal pollutants, copper resistance in Drosophila melanogaster is a useful model system with which to investigate the genetic control of the heavy metal stress response. Because heavy metal toxicity has the potential to differently impact specific tissues, we genetically characterized the control of the gene expression response to copper stress in a tissue-specific manner in this study. We assessed the copper stress response in head and gut tissue of 96 inbred strains from the Drosophila Synthetic Population Resource using a combination of differential expression analysis and expression quantitative trait locus mapping. Differential expression analysis revealed clear patterns of tissue-specific expression. Tissue and treatment specific responses to copper stress were also detected using expression quantitative trait locus mapping. Expression quantitative trait locus associated with MtnA, Mdr49, Mdr50, and Sod3 exhibited both genotype-by-tissue and genotype-by-treatment effects on gene expression under copper stress, illuminating tissue- and treatment-specific patterns of gene expression control. Together, our data build a nuanced description of the roles and interactions between allelic and expression variation in copper-responsive genes, provide valuable insight into the genomic architecture of susceptibility to metal toxicity, and highlight candidate genes for future functional characterization.
Can Social Mobility Impact Frailty Trajectories of Chinese Adults in Later Life? A Nationwide Longitudinal Study
Authors: Guo Yujia , Yang Fan
Published: January 2024

Background and Objectives

Evidence remains unclear on the impact of life-course socioeconomic position (SEP) mobility on frailty trajectories in later life. We aim to examine the longitudinal effects of social mobility on frailty trajectories among Chinese middle-aged and older populations.

Research Design and Methods

A total of 13 239 participants aged 45 and older from the 2011–2018 China Health and Retirement Longitudinal Study were analyzed. Based on changes in SEP from childhood to adulthood, 5 patterns of social mobility were established. A 32-item deficit cumulative frailty index (FI) was developed to evaluate frailty trajectories at each follow-up. Linear mixed-effects models were used to examine the longitudinal association of the 5 social mobility patterns with the frailty trajectory.

Results

The trajectory of late-life FI increased across all 5 social mobility groups during the follow-up. The FI trajectory had the largest disparity between stable high SEP and stable low SEP, with a faster increase in FI of 0.489 (95% confidence interval [CI]: 0.327–0.650, p < .001) in the stable low versus stable high SEP group. The FI trajectories of individuals in the upward and downward mobility groups fall between those in the stable high SEP and low SEP groups. Specifically, compared to the stable high SEP group, the increase in FI was 0.229 (95% CI: 0.098–0.360, p = .001) faster in the downward mobility group, and 0.145 (95% CI: 0.017–0.273, p = .03) faster in the upward mobility group. The impact of social mobility on frailty trajectories was more pronounced among middle-aged adults and women.

Discussion and Implications

These findings emphasize that policies to identify vulnerable populations and reduce frailty inequalities should focus on the socioeconomic environment across the life course, with particular attention paid to those with consistently low SEP and downward mobility.
Exploring health equity in Lesotho’s Child Grants Programme
Authors: Besnier Elodie , Kotzias Virginia , Hlabana Thandie , Beck Kathryn , Sieu Céline , Muthengi Kimanzi
Published: January 2024

Despite their growing popularity, little is known about how cash transfers (CTs) can affect health equity in targeted communities. Lesotho’s Child Grants Programme (CGP) is an unconditional CT targeting poor and vulnerable households with children. Started in 2009, the CGP is one of Lesotho’s key programmes in developing the country’s social protection system. Using the CGP’s early phases as a case study, this research aims to capture how programme stakeholders understood and operationalized the concept of health equity in Lesotho’s CGP. The qualitative analysis relied on the triangulation of findings from a desk review and semi-structured key informant interviews with programme stakeholders. The programme documents were coded deductively and the interview transcripts inductively. Both materials were analysed thematically before triangulating their findings. We explored determining factors for differences or disagreements within a theme according to the programme’s chronology, the stakeholders’ affiliations and their role(s) in the CGP. The definitions of health equity in the context of the CGP reflected an awareness among stakeholders of these issues and their determinants but also the challenges raised by the complex (or even debated) nature of the concept. The most common definition of this concept focused on children’s access to health services for the most disadvantaged households, suggesting a narrow, targeted approach to health equity as targeting disadvantages. Yet, even the most common definition of this concept was not fully translated into the programme, especially in the day-to-day operations and reporting at the local level. This operationalization gap affected the study of selected health spillover effects of the CGP on health equity and might have undermined other programme impacts related to specific health disadvantages or gaps. As equity objectives become more prominent in CTs, understanding their meaning and translation into concrete, observable and measurable applications in programmes are essential to support impact.
Modeling Shiga toxin-induced human renal-specific microvascular injury
Authors: Whelan Russell , Lih Daniel , Xue Jun , Himmelfarb Jonathan , Zheng Ying
Published: January 2024

Shiga toxin (Stx) causes significant renal microvascular injury and kidney failure in the pediatric population, and an effective targeted therapy has yet to be demonstrated. Here we established a human kidney microvascular endothelial cell line for the study of Stx mediated injuries with respect to their morphologic, phenotypic, and transcriptional changes, and modeled Stx induced thrombotic microangiopathy (TMA) in flow-mediated 3D microvessels. Distinct from other endothelial cell lines, both isolated primary and immortalized human kidney microvascular endothelial cells demonstrate robust cell-surface expression of the Stx receptor Gb3, and concomitant dose-dependent toxicity to Stx, with significant contributions from caspase-dependent cell death. Use of a glucosylceramide synthase inhibitor (GCSi) to target disruption of the synthetic pathway of Gb3 resulted in remarkable protection of kidney microvascular cells from Stx injury, shown in both cellular morphologies, caspase activation and transcriptional analysis from RNA sequencing. Importantly, these findings are recapitulated in 3D engineered kidney microvessels under flow. Moreover, whole blood perfusion through Stx-treated microvessels led to marked platelet binding on the vessel wall, which was significantly reduced with the treatment of GCSi. These results validate the feasibility and utility of a bioengineered ex vivo human microvascular model under flow to recapitulate relevant blood-endothelial interactions in STEC-HUS. The profound protection afforded by GCSi demonstrates a preclinical opportunity for investigation in human tissue approximating physiologic conditions. Moreover, this work provides a broad foundation for novel investigation into TMA injury pathogenesis and treatment.

Insight Box: Shiga toxin (Stx) causes endothelial injury that results in significant morbidity and mortality in the pediatric population, with no effective targeted therapy. This paper utilizes human kidney microvascular cells to examine Stx mediated cell death in both 2D culture and flow-mediated 3D microvessels, with injured microvessels also developing marked platelet binding and thrombi formation when perfused with blood, consistent with the clinical picture of HUS. This injury is abrogated with a small molecule inhibitor targeting the synthetic pathway of the Shiga toxin receptor. Our findings shed light onto Stx-induced vascular injuries and pave a way for broad investigation into thrombotic microangiopathies.
Heat transfer analysis of Carreau–Yasuda nanofluid flow with variable thermal conductivity and quadratic convection
Authors: Akbar Asia Ali , Awan Aziz Ullah , Nadeem Sohail , Ahammad N Ameer , Raza Nauman , Oreijah Mowffaq , Guedri Kamel , Allahyani Seham Ayesh
Published: January 2024

Brownian motions and Thermophoresis are primary sources of nanoparticle diffusion in nanofluids, having substantial implications for the thermo-physical characteristics of nanofluids. With such a high need, the 2D, laminar MHD (Magnetohydrodynamic) quadratic convective stream of Carreau–Yasuda nano liquid across the stretchy sheet has been reported. The flow is caused by surface stretching. The principal purpose of this extensive study is to enhance thermal transmission. The effects of variable thermal conductivity and heat source are considered as well. The governing boundary layer equations are transmuted using similarity parameters into a series of non-linear ODEs (ordinary differential equations). The bvp4c algorithm is adopted to fix the translated system numerically. The effects of prominent similarity variables over the temperature, velocity and concentration field are graphically visualized and verified via tables. It explored that fluid’s speed diminishes for the more significant inputs of the magnetic coefficient, Brownian motion coefficient and Prandtl number. The thermal efficiency is improved for larger values of thermophoretic constant, varying thermal conductance and heat-generating parameters. The concentration field has proved to be a decreasing function of nanofluid constants.
Unraveling the rhizobial infection thread
Authors: Gao Jin-Peng , Liang Wenjie , Liu Cheng-Wu , Xie Fang , Murray Jeremy D
Published: January 2024

Most legumes can form an endosymbiotic association with soil bacteria called rhizobia, which colonize specialized root structures called nodules where they fix nitrogen. To colonize nodule cells, rhizobia must first traverse the epidermis and outer cortical cell layers of the root. In most legumes, this involves formation of the infection thread, an intracellular structure that becomes colonized by rhizobia, guiding their passage through the outer cell layers of the root and into the newly formed nodule cells. In this brief review, we recount the early research milestones relating to the rhizobial infection thread and highlight two relatively recent advances in the symbiotic infection mechanism, the eukaryotically conserved ‘MYB–AUR1–MAP’ mitotic module, which links cytokinesis mechanisms to intracellular infection, and the discovery of the ‘infectosome’ complex, which guides infection thread growth. We also discuss the potential intertwining of the two modules and the hypothesis that cytokinesis served as a foundation for intracellular infection of symbiotic microbes.
The GPU phase folding and deep learning method for detecting exoplanet transits
Authors: Wang Kaitlyn , Ge Jian , Willis Kevin , Wang Kevin , Zhao Yinan
Published: January 2024

This paper presents GPFC, a novel Graphics Processing Unit (GPU) Phase Folding and Convolutional Neural Network (CNN) system to detect exoplanets using the transit method. We devise a fast-folding algorithm parallelized on a GPU to amplify low signal-to-noise ratio transit signals, allowing a search at high precision and speed. A CNN trained on two million synthetic light curves reports a score indicating the likelihood of a planetary signal at each period. While the GPFC method has broad applicability across period ranges, this research specifically focuses on detecting ultrashort-period planets with orbital periods less than one day. GPFC improves on speed by three orders of magnitude over the predominant Box-fitting Least Squares (BLS) method. Our simulation results show GPFC achieves 97 per cent training accuracy, higher true positive rate at the same false positive rate of detection, and higher precision at the same recall rate when compared to BLS. GPFC recovers 100 per cent of known ultrashort-period planets in Kepler light curves from a blind search. These results highlight the promise of GPFC as an alternative approach to the traditional BLS algorithm for finding new transiting exoplanets in data taken with Kepler and other space transit missions such as K2, TESS, and future PLATO and Earth 2.0.
Evolving Together: Cassandra Retrotransposons Gradually Mirror Promoter Mutations of the 5S rRNA Genes
Authors: Maiwald Sophie , Mann Ludwig , Garcia Sònia , Heitkam Tony
Published: January 2024

The 5S rRNA genes are among the most conserved nucleotide sequences across all species. Similar to the 5S preservation we observe the occurrence of 5S-related nonautonomous retrotransposons, so-called Cassandras. Cassandras harbor highly conserved 5S rDNA-related sequences within their long terminal repeats, advantageously providing them with the 5S internal promoter. However, the dynamics of Cassandra retrotransposon evolution in the context of 5S rRNA gene sequence information and structural arrangement are still unclear, especially: (1) do we observe repeated or gradual domestication of the highly conserved 5S promoter by Cassandras and (2) do changes in 5S organization such as in the linked 35S-5S rDNA arrangements impact Cassandra evolution? Here, we show evidence for gradual co-evolution of Cassandra sequences with their corresponding 5S rDNAs. To follow the impact of 5S rDNA variability on Cassandra TEs, we investigate the Asteraceae family where highly variable 5S rDNAs, including 5S promoter shifts and both linked and separated 35S-5S rDNA arrangements have been reported. Cassandras within the Asteraceae mirror 5S rDNA promoter mutations of their host genome, likely as an adaptation to the host's specific 5S transcription factors and hence compensating for evolutionary changes in the 5S rDNA sequence. Changes in the 5S rDNA sequence and in Cassandras seem uncorrelated with linked/separated rDNA arrangements. We place all these observations into the context of angiosperm 5S rDNA-Cassandra evolution, discuss Cassandra's origin hypotheses (single or multiple) and Cassandra's possible impact on rDNA and plant genome organization, giving new insights into the interplay of ribosomal genes and transposable elements.
Insight into the anti-proliferation activity and photoinduced NO release of four nitrosylruthenium isomeric complexes and their HSA complex adducts
Authors: Shi Jia , Xie Leilei , Gong Wenjun , Bai Hehe , Wang Wenming , Wang Ai , Cao Wei , Tong Hongbo , Wang Hongfei
Published: January 2024

Four Ru(II)-centered isomeric complexes [RuCl(5cqn)(Val)(NO)] (1-4) were synthesized with 5cqn (5-chloro-8-hydroxyquinoline) and chiral Val (Val = L- or D-valine) as co-ligand, and their structures were confirmed using the X-ray diffraction method. The cytotoxicity and photodynamic activity of the isomeric complexes and their human serum albumin (HSA) complex adducts were evaluated. Both the isomeric complexes and their HSA complex adducts significantly affected HeLa cell proliferation, with an IC50 value in the range of 0.3–0.5 μM. The photo-controlled release of nitric oxide (NO) in solution was confirmed using time-resolved Fourier transform infrared and electron paramagnetic resonance spectroscopy techniques. Furthermore, photoinduced NO release in living cells was observed using a selective fluorescent probe for NO. Moreover, the binding constants (Kb) of the complexes with HSA were calculated to be 0.17–1.98 × 104 M−1 and the average number of binding sites (n) was found to be close to 1, it can serve as a crucial carrier for delivering metal complexes. The crystal structure of the HSA complex adduct revealed that one [RuCl(H2O)(NO)(Val)]+ molecule binds to a pocket in domain I. This study provides insight into possible mechanism of metabolism and potential applications for nitrosylruthenium complexes.
Seasonal variability drives differences in the structure of the calanoid copepod community in two contrasting regions of the Gulf of Mexico
Authors: Gaona-Hernández Aurora , Suárez-Morales Eduardo , Linacre Lorena , Compaire Jesus C , Lara-Lara J Rubén , Herzka Sharon Z
Published: January 2024

Calanoid copepods (CC) are key contributors to the biological carbon pump and pelagic trophic dynamics. The deep-water regions of Perdido and the Bay of Campeche in the western and southern Gulf of Mexico (GM), respectively, differ in hydrography and productivity, leading to potential differences in copepod biomass and community structure. Zooplankton (0-200 m) were collected from the shelf edge to the deep-water region during the winter and summer autumn 2016. Calanoids contributed 38-60% of total zooplankton biomass and 55-70% of overall copepod abundance. The Bay of Campeche had the highest total zooplankton biovolume (287±120 ml 1000 m−3) and total mean copepod abundance (CC and non-calanoids ~146,000 ind. 1000 m−3) during summer-autumn, likely resulting from cross-shelf nutrient transport fueling local productivity. Adult females dominated calanoid numerical abundance (43-50%), thus suggesting a high reproductive potential. Cluster analysis showed differences between seasons (~40% dissimilarity) but not regions. Environmental conditions explained 22% of the variability in community composition; the winter assemblage was significantly related to oxygen concentrations, whereas the summer-autumn community was related to warmer conditions and higher integrated chlorophyll-a concentrations. The CC community responded to seasonal changes more than regionally related hydrographic differences, with likely implications for organic matter cycling and export.
Rice LIKE EARLY STARVATION1 cooperates with FLOURY ENDOSPERM6 to modulate starch biosynthesis and endosperm development
Authors: Yan Haigang , Zhang Wenwei , Wang Yihua , Jin Jie , Xu Hancong , Fu Yushuang , Shan Zhuangzhuang , Wang Xin , Teng Xuan , Li Xin , Wang Yongxiang , Hu Xiaoqing , Zhang Wenxiang , Zhu Changyuan , Zhang Xiao , Zhang Yu , Wang Rongqi , Zhang Jie , Cai Yue , You Xiaoman , Chen Jie , Ge Xinyuan , Wang Liang , Xu Jiahuan , Jiang Ling , Liu Shijia , Lei Cailin , Zhang Xin , Wang Haiyang , Ren Yulong , Wan Jianmin
Published: January 2024

In cereal grains, starch is synthesized by the concerted actions of multiple enzymes on the surface of starch granules within the amyloplast. However, little is known about how starch-synthesizing enzymes access starch granules, especially for amylopectin biosynthesis. Here, we show that the rice (Oryza sativa) floury endosperm9 (flo9) mutant is defective in amylopectin biosynthesis, leading to grains exhibiting a floury endosperm with a hollow core. Molecular cloning revealed that FLO9 encodes a plant-specific protein homologous to Arabidopsis (Arabidopsis thaliana) LIKE EARLY STARVATION1 (LESV). Unlike Arabidopsis LESV, which is involved in starch metabolism in leaves, OsLESV is required for starch granule initiation in the endosperm. OsLESV can directly bind to starch by its C-terminal tryptophan (Trp)-rich region. Cellular and biochemical evidence suggests that OsLESV interacts with the starch-binding protein FLO6, and loss-of-function mutations of either gene impair ISOAMYLASE1 (ISA1) targeting to starch granules. Genetically, OsLESV acts synergistically with FLO6 to regulate starch biosynthesis and endosperm development. Together, our results identify OsLESV-FLO6 as a non-enzymatic molecular module responsible for ISA1 localization on starch granules, and present a target gene for use in biotechnology to control starch content and composition in rice endosperm.
Uncertainty quantification in computed tomography pulmonary angiography
Authors: Rambojun Adwaye M , Komber Hend , Rossdale Jennifer , Suntharalingam Jay , Rodrigues Jonathan C L , Ehrhardt Matthias J , Repetti Audrey
Published: January 2024

Computed tomography (CT) imaging of the thorax is widely used for the detection and monitoring of pulmonary embolism (PE). However, CT images can contain artifacts due to the acquisition or the processes involved in image reconstruction. Radiologists often have to distinguish between such artifacts and actual PEs. We provide a proof of concept in the form of a scalable hypothesis testing method for CT, to enable quantifying uncertainty of possible PEs. In particular, we introduce a Bayesian Framework to quantify the uncertainty of an observed compact structure that can be identified as a PE. We assess the ability of the method to operate under high-noise environments and with insufficient data.