bluuebunny/crossref_metadata_2025 huggingface dataset:
N39 Point of care ultrasound in Inflammatory Bowel Disease patients, being introduced in an Irish context - key stakeholder's perspectives
Authors: O Sullivan C , Hegarty J , Sugrue K , Gleeson S , McCarthy J , Buckley M , Moran C , Sheehan D , McDonald C , Burton A
Published: January 2025

Background

Point of care ultrasound is a real-time, non-invasive imaging modality used across many disciplines for several years, including in Inflammatory Bowel Disease (IBD) patients in central Europe. However, it is only recently beginning to be introduced in an Irish context. This study aims to explore the perspectives of key stakeholders in IBD in Ireland, towards the introduction of point of care ultrasound (PoCUS) amongst IBD patients. The secondary aim is to clarify if key stakeholders are supportive of nurse performed PoCUS in IBD if a referral pathway was to become available in an Irish context.

Methods

A quantitative cross sectional, descriptive online survey was developed to collect anonymous responses from key stakeholders in the IBD clinical care context in Ireland. The email inviting potential respondents to consider participation in the survey was distributed by two professional bodies – The Irish Society of Gastroenterology and Inflammatory Bowel Disease Nurses Association of Ireland. Analysis included a descriptive modelling of the data using logistic regression.

Results

In completing the survey, 25% of respondents confirmed that they had an ultrasound service for IBD patients while 44% (n=42) have future plans to develop one. Among the surveyed doctors, only 9% (n=9) have undergone training in PoCUS, while 79% of all respondents express intentions to pursue training or are open to considering it in the future. On average, respondents disagreed that PoCUS will replace Colonoscopy and MRI in the future, with a mean score of 2.47 (SD 1.24). Doctors and nurses perceive having access to PoCUS as important for patient outcome and quality of care, mean 4.06 (SD 1.02). Overall, 51% (n=48) of respondents reported having no fears or reservations associated with using PoCUS in clinical practice. Both doctors and nurses exhibited positive attitudes towards nurse-led PoCUS in IBD, highlighting its perceived cost effectiveness, as evidenced by a mean score of 4.38 (SD 1.01).

Conclusion

Key findings highlight a majority of respondents have plans to develop a PoCUS service and undertake training to improve quality of care for patients with IBD. The vast majority of respondents support the introduction of nurse performed PoCUS in the Irish setting.

References

Dolinger, M. Kayal, M. Intestinal Ultrasound Is the Ideal Patient-Centric, Point-of-Care Tool for Clinical Decision Making in the Inflammatory Bowel Disease Practice, Crohn's & Colitis 360, Volume 5, Issue 3, July 2023, otad029, available at: https://doi.org/10.1093/crocol/otad029.
N44 Telenursing for patients with inflammatory bowel disease: an interview study of nurses
Authors: Kawakami A , Tanaka M , Sakagami K , Moribe Y , Kunisaki R
Published: January 2025

Background

Telephone nursing services for people with inflammatory bowel disease are widespread internationally. Nurses supporting this patient group require skills to treat and manage a wide range of symptoms. However, nurses who provide telenursing for people with inflammatory bowel disease face a range of challenges, some of which are specific to telenursing for this condition. We aimed to investigate telenursing specifically for people with inflammatory bowel disease. In particular, we sought to identify nurses’ practices and what they considered to be important in telenursing.

Methods

We carried out semi-structured interviews with 20 nurses in Japan with extensive experience providing telenursing for people with inflammatory bowel disease. Participants were selected by convenience sampling. First, nurses were asked about the main topics about which they were consulted by phone, and their responses to each one. The interviewees were asked about their perceptions of what was important, and the specific actions involved in answering the phone. Data were analysed using inductive content analysis. Reporting followed the Standards for Reporting Qualitative Research.

Results

All 10 facilities provided telephone consultations without screens. Nurses had a mean duration of 9.1 years of telenursing experience. We extracted eight categories and 21 sub-categories of practice, as follows. When giving patients information about the availability of telenursing, nurses provide education and information to ensure that telephone consultations will be effective (A). When nurses receive telephone calls from people with inflammatory bowel disease (B), they work to understand the situation (C). When the call is about a patient’s worsening physical condition, nurses evaluate the patient’s physical condition (D), make decisions (E), and recommend a course of action to the caller (F). For consultations and requests about other issues, nurses act as the initial contact but share the responsibility for decision-making with other professionals (G). In some cases, nurses might contact patients (H). Three categories were identified as important elements in telenursing practice: establishing a coordinated system, clarifying the role of telenursing and improving skills.

Conclusion

We identified several issues that were specific to providing telenursing for patients with inflammatory bowel disease. Addressing these issues could improve nursing practice in this field. Better understanding of telenursing practices and perspectives will help nurses to appreciate the basic practice and scope of work involved in telenursing, and may improve patient care.
N53 Managing an ever-increasing inflammatory bowel disease helpline service
Authors: Scott G , Brown A , Roads N , Abreu B , Rai K , Naeck-Boolauky P , Loxley J
Published: January 2025

Background

Inflammatory bowel disease helplines have been initiated by Trusts throughout the country over many years. However many of them are not adequately job planned and have also seen a dramatic rise in calls over the years. Our Trust operates a helpline over 3 acute hospital sites. Previously calls were not accounted for financially and calls not documented in patient notes. Previously all helpline messages were retrieved by one of the clinical nurse specialists which took a considerable amount of nursing time.

Methods

The nurses on each site all undertake a number of clinical shifts per week answering helpline calls. Previously a list of patients was compiled from patient 1 onwards and staff were unable to prioritise any calls. The consultation is then dictated via a speech recognition system and a letter is generated and sent to the general practitioner. . The time that the call takes is also noted, to enable better job planning. All of the helpline calls are audited and trends and number of calls are analysed.

Results

We enlisted the support of our IBD coordinator who reviewed the helpline system and looked for improvements. They took over listening to and retrieving all messages left on the answerphone thus saving nursing time. They also changed the reporting system to a tabulated excel spreadsheet which enabled all calls to be effectively triaged and acted on in a timely manner. All calls are then added to a central spreadsheet which then categorises the calls into flare advice, medicines advice, investigation issues, appointment issues, etc.

It has also enabled better job planning and it has highlighted the increased number of calls that are taken by the nursing team and that they have been safely managed and accounted for. it has also enabled the team to trend the calls that are taken and the reasons why patients phone our helplines.

Conclusion

This project has shown a dramatic increase in activity for the IBD nurses. It has also highlighted the financial activity of the service and the contribution this provides to the gastroenterology department. This project has not only saved nursing time that should be spent with patients but ensured that patients are reviewed timely. This audit has since been utilised by the South East IBD Network. This project could not have been a success without the vision of Adam our IBD coordinator and the hard working IBD nurses of East Kent Hospitals University Foundation Trust.
Microscopic colitis as pre-inflammatory bowel disease model: from early-stage to tissular endpoint fibrosis
Authors: Escudero-Hernández C
Published: January 2025

Background and aims

Inflammatory bowel disease (IBD) cause chronic relapsing-remitting inflammatory flares in the gastrointestinal tract, resulting in abdominal pain, diarrhea, and gut dysmotility in non-destructive collagenous and lymphocytic microscopic colitis. In addition, classic IBDs Crohn´s disease and ulcerative colitis cause bloody diarrhea and extraintestinal symptoms. Non-destructive IBDs seem to restrain an overt immune response that will damage the tissue and impair wound healing. Thus, I will work under the premise that non-destructive IBDs are undeveloped forms of classic IBDs.

Methods

First, I aim to deeply characterize and compare immune cells and their activation levels in all forms of IBD using “immunomics” (spectral/computational cytometry) and validate my previous finding of two subtypes of lymphocytic colitis. To identify the microbiota that adheres to intestinal epithelial cell (IEC) and therefore alter permeability, and induce collagen deposition, I will coculture IEC and fibroblasts in organ-on-a-chip platforms to mimic gut conditions, including microflow shear stress. I will stimulate chips with patient-derived microbiota-containing luminal content or homogenized biopsies and resections from collagenous colitis (characterized by pathogenic collagen position) and intestinal fibrosis (a major, irreversible IBD complication that increases mortality), respectively, and study using different sequencing techniques. Of note, collagenous colitis could resemble early stages of intestinal fibrosis. My third objective aims to test my previous observation that regulatory B-cells in collagenous colitis might be responsible of restricting overt inflammation.

Anticipated impact

I will adapt spectral cytometry panels to characterize the state of mucosal B- and plasma cells. The support of my host, the well-established IBD immunologist Assoc. Prof. David Bernardo at the Institute of Biomedicine and Molecular Genetics (Valladolid, Spain, h-index=33) and me as coordinator of the biobank for the European Microscopic Colitis Group, ensure the feasibility to complete my ambitious research agenda and make a great impact on IBD field to discover disease-specific biomarkers, pathomechanisms, and new druggable targets.
Patterns and mechanisms of visceral and rectal hypersensitivity in patients with ulcerative colitis in remission
Authors: Trikola A
Published: January 2025

Background and aims

Ulcerative colitis (UC) is a chronic inflammatory disorder affecting the colorectum, with a disease course characterized by periods of flare and remission. Despite the progression of medical therapy and although the clinical and laboratory findings of UC improve during remission, chronic abdominal pain and changes in the frequency and the consistency of stool are frequently observed. It has been reported that abdominal pain occurs in 20-50% of IBD patients even when clinical and endoscopic remission is achieved. Previous studies have suggested that this may reflect visceral hypersensitivity in these patients, with lower thresholds for pain sensation.

The aim of this study is to provide a granular classification of symptom patterns and physiological abnormalities in distinct cohorts among patients with UC in remission, and to dissect the underlying mechanisms.

Methods

The aim of this study is to provide a granular classification of symptom patterns and physiological abnormalities in distinct cohorts among patients with UC in remission, and to dissect the underlying mechanisms. The project will build on an ongoing Greek study (for which the applicant is also the lead investigator). Using validated symptom questionnaires and high resolution anorectal manometry, the Greek cohort will identify clusters of symptomatology and associated physiological changes. Then, as part of this proposal, we will use the same questionnaires in a cohort of patients in Cambridge, UK to validate clusters of symptoms observed. We will use biopsies< from these patients to confirm the presence of a pro-nociceptive bowel environment in patients with pain in remission and investigated how this can be targeted with specific drugs.

Anticipated impact

The result will be a more detailed understanding of the patterns of functional symptoms experienced by patients with UC in remission, along with the functional correlates and putative nociceptive mediators. This will provide immediate insight into how to support patients with these symptoms as well as supporting future studies using therapeutic agents to alleviate symptoms in subgroups of patients.
Evaluating protein SUPPLEMENTation in Ulcerative Colitis (SUPPLEMENT-UC)
Authors: Day A S , Davis R H , Bibb L , Edwards S , Forster S C , Gibson P R , Bryant R V
Published: January 2025

Background and aims

A higher dietary protein intake has overall health and body composition benefits but also has the propensity to drive inflammation in ulcerative colitis (UC). This study aims to investigate whether recreational animal-based protein supplementation affects ability to maintain remission in adults with clinically quiescent UC.

Methods

Twenty-four adults with quiescent UC (Simple Clinical Colitis Activity Index (SCCAI) ≤2) on stable therapy will be randomised to a 24-week double blind, parallel, placebo-controlled protein supplement intervention in addition to habitual diet. The primary outcome is maintenance of remission (defined as SCCAI ≤2) at 24 weeks, relapse being defined as an increase in SCCAI ≥2 points and/or escalation of medical therapy. Disease activity will be assessed using clinical, biochemical and sonographic indices. Adherence, tolerability and safety will be measured using pre-defined categories and 100-mm visual analogue scales. Dietary intake and change in body composition will be measured along with biomarkers and metabolites of fermentation in faecal, blood and urine specimens.

Anticipated impact

This trial addresses one of the top three international IBD research priorities - the role of diet to induce/maintain remission in UC. It will be the first ever study to investigate whether animal-based protein supplements influence the ability of adults with quiescent UC to maintain remission, and to explore the mechanistic basis and relationship between dietary substrate, gut microbiota, and disease activity. The trial results are anticipated to inform UC treatment paradigms by demonstrating dietary factors influence disease activity and dietary advice can be readily incorporated into current UC treatment paradigms as a cost neutral, adjunctive therapy to optimise response to existing therapies. The ultimate goal is to optimise therapeutic outcomes and improve quality of life for people with UC.
Caudovirales as a Trigger of Molecular Mimicry in Crohn’s Disease
Authors: Errico C
Published: January 2025

Background and aims

Dysregulation of gut microbiota has been implicated in inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Recent studies have highlighted the role of gut virome dysbiosis in CD pathogenesis and the expansion of the Caudovirales of bacteriophages in patients, confirmed also in the IBD Transcriptome and Metatranscriptome Meta-Analysis framework. Additionally, preliminary data showed that, among the Caudovirales, the Proteus virus Isfahan species was the most abundant in CD by comparison with the healthy, while no positivity was shown by UC patients. This result prompted us to hypothesize that this viral species might lead to a molecular mimicry mechanism as part of IBD pathogenesis, as previously suggested. Thus, we assessed whether Proteus virus Isfahan encoded proteins could be similar to the human. We analysed the viral sequence and 3D structural homologies by NCBI blast and iPBA in silico tools. Interestingly, two viral encoded proteins, gp16 and gp82, resulted as highly homologous with the human thymidylate synthase and dCMP deaminase, respectively. Based on our preliminary evidence, we aim to demonstrate a possible molecular mimicry mechanism directed by virome proteins and their involvement in CD pathogenesis

Methods

“In vitro” experiments will assess the impact of Proteus virus Isfahan proteins on immune cells and T-cell responses, aiming to elucidate potential mechanisms of viral-induced autoimmunity and tissue damage. Additionally, we will collect mucosal biopsies from CD to test Proteus virus Isfahan positivity and define a cohort of patients harbouring this gut virome species. By multivariate analysis, we will understand whether viral species positivity correlates with clinical characteristics, pointing to virome-based biomarkers as capable of stratify patients a priori.

Anticipated impact

The project's significance is to uncover novel insights into the relationship between viral dysbiosis, molecular mimicry, and CD pathogenesis, offering opportunities for tailored therapies in a defined cohort of patients.
Immunometabolic landscaping in Crohn’s disease creeping fat – Does fat matter?
Authors: Haag L M
Published: January 2025

Background and aims

The study proposed herein aims to explore the complex immunometabolic landscape of Creeping Fat (CF) in Crohn's disease (CD) ileitis, an area that remains largely unexplored. Our hypothesis posits the existence of distinct sub-entities within mesenteric adipose tissue, characterized by unique metabolic states in immune cells, non-immune cells, and adipocytes. The primary objective is to elucidate the immunometabolic environment within ileal CF, leveraging an advanced Imaging Mass Cytometry (IMC)-based methodology.

Methods

Employing a 37-marker IMC panel, we will conduct comprehensive spatial and metabolic profiling of adipose and intestinal tissues from a cohort of 50 patients, including those with CD and ulcerative colitis (UC), and compare these profiles with samples from bariatric surgery patients. This approach enables single-cell level analysis with spatial resolution, uncovering the metabolic states and signatures of various cell types. Previous work in our group has already demonstrated the utility of this technique in revealing significant variations in cell metabolism across different inflammatory states and cell types in CD. Our methodology integrates the study of immune cell clusters, metabolic states, and subtypes with distinct metabolic signatures. By comparing metabolic signatures in adipose tissues with those in inflamed ileal mucosal tissue, we aim to establish an understanding of metabolic processes within CF.

Anticipated impact

Anticipated impact includes the identification of unique immunometabolic signatures in CF, providing new insights into the pathomechanisms of CD. This could lead to novel therapeutic targets focusing on the metabolism of specific cell types within CF. The study holds the potential to reshape our understanding of CD, paving the way for more targeted and effective treatments for this debilitating disease. Given our established expertise, robust methodology, and comprehensive cohort, this research is poised to offer significant contributions to the field of immunometabolism in IBD, enhancing our understanding of CF and its role in CD.
Optimizing Appendectomy in Ulcerative Colitis: Predictive Markers and Mechanistic Insights
Authors: Becker M A J , Wildenberg M E , Buskens C J
Published: January 2025

Background and aims

Two recent studies from our group have demonstrated a beneficial effect of appendectomy in ulcerative colitis (UC): the ACCURE and COSTA trial show a 20% reduced recurrence rate and >20% increase in induction of remission when compared to medical treatment. However, like for all therapeutic interventions in IBD, not all patients respond equally, leaving room for optimisation. Preliminary RNA sequencing results suggested two subtypes of appendices. Clustering within subtype was seen based on inflammatory pathways which was associated with response. This was confirmed by histology, where patients with a more pro-inflammatory profile were more likely to respond.

The aim of the current project is to improve efficacy of appendectomy by better patient selection through predictive markers and to elucidate the biological mechanisms of action of appendectomy in UC.

Methods

We will validate our preliminary data regarding gene signatures predictive for response to appendectomy and extend these results to the coecal base, enabling prediction of response from endoscopic biopsies and thus improving applicability. In addition, we will focus on the mechanisms of action of appendectomy by targeting the two theories: Firstly, using single cell RNA sequencing we will identify the cellular compartment expressing the genesets associated with response and determine the role of host cells. Secondly, using 16S sequencing of the microbiome of appendix and coecum will allow evaluation of the role of the microbiome.

During the ACCURE and COSTA trial, appendiceal samples (n>100) have been stored for future analysis. This enables the direct start of this experimental study and completion within the 1 year timeframe.

Anticipated impact

This project aims to predict response and clarify the mode of action of appendectomy in UC, contributing to patient stratification. As a simple, safe, and low-cost procedure, appendectomy has significant potential for UC treatment in both high- and low/middle-income countries.
Biomarkers of dietary intake in faeces of children with Crohn’s disease and their role in disease recurrence following treatment with exclusive enteral nutrition
Authors: Gerasimidis K , Gkikas K , Rentaki P , Morrison D , Russell R , Rattray N , Havlik J
Published: January 2025

Background and aims

This study aims to profile biomarkers of dietary intake in faeces of children with Crohn’s disease (CD) and explore their role in disease recurrence following induction treatment with exclusive enteral nutrition.

Methods

We will profile and quantify biomarkers of dietary intake in 928 banked faecal samples of 116 children with CD collected during the first 30 days of food reintroduction, following successful treatment with exclusive enteral nutrition (EEN), and in spot samples from 53 matched healthy controls. In faecal samples, a wide range of carbohydrates (e.g. galactose, rhamnose, glucose, xylose), polysaccharides (e.g resistant starch) and oligosaccharides (e.g. β-fructans), total nitrogen, as well as nitrogen-containing compounds (e.g. amino acids, dipeptides) will be measured with a combination of 1H-NMR, UHPLC-MS, anion exchange chromatography, the Kjeldahl AOAC method and proprietary kits.

Faecal biomarkers of dietary intake will be associated with risk of disease recurrence (indicated by the rapid rise in faecal calprotectin) during the first 30 days of food reintroduction, following successful treatment with EEN. Next, this study will explore whether identified biomarkers of dietary intake in faeces relate with patients’ actual dietary intake, and whether the two datasets complement or supersede each other in prediction of disease recurrence. Last, we will identify common dietary biomarkers of disease recurrence between two distinct cohorts of patients; one which returned to unrestricted diet, post-EEN, and another which followed a novel exclusion diet (CD-TREAT) for the management of CD.

Anticipated impact

This study has the potential to address one of the most frequently asked questions from patients to healthcare professionals; “What should I eat to control my disease and prevent disease relapse?” Identification of dietary triggers may lead to the development of food reintroduction protocols following EEN completion; hence offering better long-term disease control and improving the quality of life of patients with CD.
Patient and public involvement and engagement to inform an adaptive platform trial using a multi-arm multi-stage (MAMS) approach in Ulcerative colitis and Crohn’s disease
Authors: Radford S
Published: January 2025

Background and aims

There is an abundance of advanced therapies in use in treating IBD. The growing number of available treatments for IBD raises questions of comparative efficacy, safety, treatment strategies and sequences. While head-to-head blinded controlled trials are the ideal method for comparing the efficacy of different drugs, practical limitations make it challenging to conduct multiple trials encompassing all available treatment options. The aim is to explore and define which clinical, endoscopic, imaging, and biochemical outcomes are ‘critical’ and ‘important’ definitions of interim and definitive outcomes to IBD stakeholders

Methods

A mixed methods approach will be used in 4 work packages; setting up expert study team made up of UK based patient experts and IBD Nurses from around Europe to finalise the design of a Delphi survey, Delphi survey to establish critical and important clinical outcome measures as identified by key stakeholders, exploratory qualitative survey will be used to capture deeper meaning and understanding of some of the contextual factors around the answers given to the Delphi survey and a final consensus meeting for stakeholders to bring together all findings and the key outcome set for a MAMS trial of advanced therapies in IBD will be defined.

Anticipated impact

A definitive list of stakeholder-identified critical and important clinical outcomes for IBD therapy and downstream research design.
Left bundle branch area pacing in children: case series
Authors: Jędrzejczyk-Patej Ewa , Mazurek Michał , Kowalski Oskar , Szulik Mariola , Tyc Filip , Pietruczuk Armin , Lenarczyk Radosław , Kalarus Zbigniew
Published: January 2025

Background

Left bundle branch area pacing (LBBAP) is a new concept that provides physiological pacing with a narrow QRS duration. Recently published data suggest that LBBAP may prevent deleterious effects of right ventricular pacing, namely pacemaker-induced cardiomyopathy, especially in patients with expected high ventricular pacing burden, which may be of particular importance in children.

Case summary

Herein, we report successful implantation of Medtronic SelectSecure (Model 3830, Medtronic Inc.) right ventricle electrode in the region of left bundle branch area in three consecutive children (two 16-year-old and one 8-year-old). Indication for pacemaker implantation was third-degree atrioventricular block in all cases. Implantations were performed under general anaesthesia, and there were no acute complications. During the median follow-up of 6 months, there were no adverse events and the electrical parameters of the device remained stable.

Discussion

Compared with adult patients, implantation of pacemakers in children may still be challenging, not only because of smaller body size but also due to continuing growth and a higher rate of lead and device-related complications. We have demonstrated that implantation of LBBAP in children is feasible and could be worth considering, particularly in patients with expected high ventricular pacing burden. Further studies are needed to assess the efficacy and safety of LBBAP in children during long-term observation.
The Nevell manuscript: new evidence of 17th-century gentlewomen’s music book-sharing and education at exiled English convents
Authors: Lesemann-Elliott Caro
Published: January 2025

Scholarship on early modern English musical culture remains dominated by the activities of male musicians and male institutions. Despite the drastic growth of English convent studies as a discipline, relatively little examination by musicologists of the roles of these institutions in the production and circulation of music books or in musical networks more generally has taken place. Indeed, even those who are examining books with direct evidence of female ownership and/or usage have often only viewed the books through the lenses of male institutions. This article explores a music book that initially belonged to Ursula Nevell [Neville] (c.1653–1727), identifying the contents of the book, including new sources of music from the final quarter of the 17th century. It uncovers evidence of likely usage in the context of an exiled English convent and demonstrates that the book probably travelled across the channel several times over two generations, used by both mother and daughter, both in and out of an English convent context. The article contextualizes the book against a wider backdrop of English convent musical culture and music education at the convent schools by using new research that has been undertaken since 2011. Finally, it suggests some possibilities for how Neville’s book may have been partially produced and/or used in a convent context.
The later the better? A novel approach to estimating the effect of school starting age on ADHD and academic skills
Authors: Beck Kathryn Christine
Published: January 2025

School entry is an important life transition where early disadvantages may have consequences for children’s educational trajectory. This paper provides important evidence on the production of disadvantages by the education system using a novel approach to school starting age (SSA) which is not biased by parental resources or prior dis-advantages. By using due date from the Medical Birth Registry of Norway (MBRN) as an instrumental variable for SSA, and register data covering the entire Norwegian population, I show that a one-year increase in SSA led to a 59 per cent lower risk of being diagnosed with ADHD and significantly higher national test scores in 5th and 9th grade. Additionally, this study finds that 10.1 per cent of births are shifted from the week before the school entry cut-off to the week after. Parents with higher educational attainment are significantly more likely to shift births across the cut-off, providing a cautionary note to studies attempting to estimate causal effects of SSA using month or date of birth. Overall, this study provides important evidence one way in which inequalities are produced by the education system and how socioeconomically advantaged parents may act to mitigate these risks.
Mosaic loss of Y chromosome and mortality after coronary angiography
Authors: Weyrich Michael , Zewinger Stephen , Sarakpi Tamim , Rasper Tina , Kleber Marcus E , Cremer Sebastian , Zanders Lukas , Fleck Fenja , Siegbahn Agneta , Wallentin Lars , Abplanalp Wesley Tyler , Nerbas Linda , Fay Sandra , Eberle Aaron L , Dimmeler Stefanie , März Winfried , Speer Thimoteus , Zeiher Andreas M
Published: January 2025

Background and Aims

Acquired somatic mutations emerged as important drivers of adverse cardiovascular disease outcomes. Recently, mosaic loss of Y chromosome (LOY) in haematopoietic cells was identified to induce diffuse cardiac fibrosis in male mice. The aim of the present study was to determine the association between LOY and cardiovascular mortality in patients undergoing coronary angiography.

Methods

LOY was quantified in 1698 male participants of the LURIC study, who underwent coronary angiography, and its association with all-cause and cardiovascular mortality was determined. Furthermore, the interaction between LOY and inherited genetic susceptibility for cardiac fibrosis was assessed.

Results

The frequency of LOY steeply increased in male participants of LURIC at the age of 60 years. Loss of Y chromosome > 17% was associated with significantly higher all-cause [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.09–1.82] and cardiovascular mortality (HR 1.49, 95% CI 1.09–2.03), which was driven by a higher risk for fatal myocardial infarction (HR 2.65, 95% CI 1.46–4.81). Loss of Y chromosome > 17% was associated with a profibrotic and proinflammatory plasma protein expression profile as characterized by higher plasma levels of osteoprotegerin, matrix metalloproteinase-12, growth differentiation factor 15, heparin-binding EGF-like growth factor, and resistin. Genetic predisposition for lower myocardial fibrosis attenuated the association between LOY and cardiovascular mortality. Genome-wide methylation analyses identified differential methylation in 298 genes including ACTB, RPS5, WDR1, CD151, and ARAP1. Single-cell RNA sequencing further confirmed differential gene expression of 37 of these genes in LOY in peripheral blood mononuclear cells comprising a set of fibrosis-regulating genes including RPS5. RPS5 silencing in macrophages induced a paracrine induction of collagen expression in cardiac fibroblasts documenting a functional role in vitro.

Conclusions

LOY represents an important independent risk factor for cardiovascular mortality in male patients with coronary artery disease. Targeting LOY may represent a sex-specific personalized medicine approach.
Cardiac dysfunction related to cardiac mRNA and protein traffic impairment due to reduced unconventional motor protein myosin-5b expression
Authors: Heimerl Maren , Erschow Sergej , Müller-Olling Mirco , Manstein Dietmar J , Decher Niels , Kauferstein Silke , Jenewein Tina , Pich Andreas , Ricke-Hoch Melanie , Hilfiker-Kleiner Denise
Published: January 2025

Background and Aims

The present study analysed the expression patterns of class-5 myosin motor proteins (MYO5a, b, and c) in the heart with a specific focus on the role of MYO5b.

Methods

RNA-sequencing, quantitative real-time polymerase chain reaction, immunohistochemistry, Western blot, immunoprecipitation, and proteomics were performed in mice and human tissues. Functional analyses were performed in mice with a cardiac-specific knockout (KO) of MYO5b (αMHC-Cretg/−; MYO5bflox/flox), wild-type (WT) (MYO5bflox/flox), and αMHC-Cretg/− mice and in isolated adult cardiomyocytes. Next-generation sequencing screened for MYO5B gene variants in a cohort of sudden cardiac death in the young/sudden infant death syndrome patients.

Results

The expression of MYO5b, but not MYO5a or c, increased during postnatal cardiomyocyte maturation. Myosin-5b was reduced in end-stage failing human hearts and infarcted murine hearts. Heterozygous rare and likely pathogenic missense MYO5B gene variants (n = 6) were identified in three patients of a cohort of young patients (n = 95) who died of sudden cardiac death in the young/sudden infant death syndrome. MYO5b-KO mice revealed impaired electric conductance and metabolism, developed sarcomeric disarrangement, heart failure and death with altered mRNA levels for genes involved in sarcomere organization, fatty acid and glucose metabolism, ion channel sub-units, and Ca2+-homeostasis prior to heart failure. In cardiomyocytes, myosin-5b is associated with mitochondrial and ribosomal proteins. Myosin-5b-associated ribonucleoprotein particles (RNPs) contained mRNAs of sarcomeric, metabolic, cytoskeletal, and ion channel proteins.

Conclusions

MYO5b is the major MYO5 gene expressed in postnatal cardiomyocytes where it transports vesicles, proteins, and multi-protein complexes. Among these are mRNA/RNP complexes affecting electric conductance, sarcomere homeostasis, cell metabolism, and cytoskeletal organization. Impairment in MYO5b expression and function promotes cardiac dysfunction, heart failure, and death.
Cdr1 in focus: a personal reflection on multidrug transporter research
Authors: Prasad Rajendra
Published: January 2025

Drug resistance mechanisms in human pathogenic Candida species are constantly evolving. Over time, these species have developed diverse strategies to counter the effects of various drug classes, making them a significant threat to human health. In addition to well-known mechanisms such as drug target modification, overexpression, and chromosome duplication, Candida species have also developed permeability barriers to antifungal drugs through reduced drug import or increased efflux. The genomes of Candida species contain a multitude of drug resistance genes, many of which encode membrane efflux transporters that actively expel drugs, preventing their toxic accumulation inside the cells and contributing to multidrug resistance. This brief personal retrospective piece for the “Thematic Issue on Celebrating 30 Years of Cdr1 Research: new trends in antifungal therapy and drug resistance” looks back as to how antifungal research has shifted focus since the identification of the first multidrug transporter gene, CDR1 (Candida Drug Resistance 1), leading to new insights into how reduced azole permeability across Candida cell membranes influences antifungal susceptibility.
The rise of goldfishes in North America
Authors: Massey Melanie D , Claus Catalina , Hubbard Justin A G , Illyes Edina , Marques Piatã , Ricciardi Anthony , Schubert Emma L , Storey Kate , Mandrak Nicholas E
Published: January 2025

Goldfish Carassius auratus is a longstanding global invader that has entered a new phase in its invasion history, spreading into new geographical areas and reaching larger body sizes and abundances than previously recorded. In this Perspective, we present evidence that C. auratus and other goldfishes Carassius spp. represent an increasing, yet overlooked, risk to North American freshwaters. We synthesize existing knowledge on the history, physiology, impacts, and current management of goldfishes in North America. We also identify knowledge gaps in our understanding of the biology of goldfishes as they relate to invasive species management and recommend interdisciplinary approaches for addressing the growing Goldfish problem in North America.
PyDRex: predicting crystallographic preferred orientation in peridotites under steady-state and time-dependent strain
Authors: Bilton Leon , Duvernay Thomas , Davies D Rhodri , Eakin Caroline M
Published: January 2025

Crystallographic preferred orientation (CPO) of peridotite minerals is frequently invoked to explain the widespread dependence of seismic wave speed on propagation direction in Earth’s mantle—a property known as seismic anisotropy. As established by rock mechanics experiments, CPO constitutes a direct signature of past and ongoing strain regimes experienced by rocks during mantle flow. Therefore, an improved understanding of CPO generation promises to yield valuable information on the rheology and corresponding deformation mechanisms activated through mantle dynamics. Simulating CPO in geodynamical models is computationally challenging and has often been restricted to steady-state mantle flows. However, within Earth’s vigorously convecting mantle the steady-state assumption is questionable, thus motivating the need to couple CPO simulations with time-evolving mantle flow models. Here, we present a new Python implementation of the D-Rex CPO model, called PyDRex, which predicts salient features of mineral grain size and orientation evolution whilst providing a well-documented, user-friendly interface that supports flexible coupling to geodynamical modelling frameworks. PyDRex also packages numerous post-processing routines for strain analysis and visualization of grain orientation distributions. We provide a set of benchmark simulations based on previous D-Rex implementations that validate PyDRex and demonstrate sensitivities to model parameters for both steady-state and time-dependent flows. Analysis of benchmark results highlights the role of dynamic recrystallization in controlling competing grain growth in both the softest and hardest crystallographic orientations. When employing a commonly used value for the grain boundary mobility parameter ($M^{\ast }=125$), we also find that transient CPO textures are generally not well resolved if crystals are represented by fewer than 5000 ‘grains’ (weighted orientation samples)—a configuration rarely employed in most previously published studies. Furthermore, kinematic corner-flow models suggest that CPO produced at mid-ocean ridges has a nonlinear dependence on depth, which implies that even ostensibly simple mantle flows can result in complex distributions of seismic anisotropy. Our analyses motivate further experimental calibration of parameters controlling dynamic recrystallization and potential improvements to the numerical treatment of subgrain nucleation.
A Short Proof That Rezk’s Nerve Is Fully Faithful
Authors: Hebestreit Fabian , Steinebrunner Jan
Published: January 2025

We give a simple proof that complete Segal animae are equivalent to categories.
Surfactin facilitates establishment of Bacillus subtilis in synthetic communities
Authors: Lozano-Andrade Carlos N , Dinesen Caja , Wibowo Mario , Bach Nil Arenos , Hesselberg-Thomsen Viktor , Jarmusch Scott A , Strube Mikael Lenz , Kovács Ákos T
Published: January 2025

Soil bacteria are prolific producers of a myriad of biologically active secondary metabolites. These natural products play key roles in modern society, finding use as anti-cancer agents, as food additives, and as alternatives to chemical pesticides. As for their original role in interbacterial communication, secondary metabolites have been extensively studied under in vitro conditions, revealing many roles including antagonism, effects on motility, niche colonization, signaling, and cellular differentiation. Despite the growing body of knowledge on their mode of action, biosynthesis, and regulation, we still do not fully understand the role of secondary metabolites on the ecology of the producers and resident communities in situ. Here, we specifically examine the influence of Bacillus subtilis-produced cyclic lipopeptides during the assembly of a bacterial synthetic community, and simultaneously, explore the impact of cyclic lipopeptides on B. subtilis establishment success in a synthetic community propagated in an artificial soil microcosm. We found that surfactin production facilitates B. subtilis establishment success within multiple synthetic communities. Although neither a wild type nor a cyclic lipopeptide non-producer mutant had a major impact on the synthetic community composition over time, both the B. subtilis and the synthetic community metabolomes were altered during co-cultivation. Overall, our work demonstrates the importance of surfactin production in microbial communities, suggesting a broad spectrum of action of this natural product.
Resistance to empirical antibiotics in urinary tract infections caused by Enterobacterales in the East of England
Authors: Drazich-Taylor Stuart , Dominic Catherine , Moore James , Craine Ashley , Nwaka Davis
Published: January 2025

Objectives

To characterize resistance rates in urinary tract infections caused by Enterobacterales to first- and second-line antibiotics.

Methods

Positive urine cultures examined by the Eastern Pathology Alliance network from September 2018 to September 2023 were retrospectively analysed. Enterobacterales from non-pregnant adults were included. Resistance to cefalexin, nitrofurantoin, trimethoprim, pivmecillinam and fosfomycin was investigated.

Results

A total of 193 137 samples from 99 635 patients met inclusion criteria. The mean number of episodes per patient was 1.94, with a range of 1–55 episodes over the 5 year period. Patients were predominantly of female sex (76.6%) and of an older age (mean age 66.4 ± 19.5 SD). Escherichia coli was the commonest organism isolated (73%) followed by undifferentiated coliforms (16%), Proteus spp. (6%) and Klebsiella pneumoniae (2%). Across all samples, trimethoprim resistance was high at 27%, with lower cefalexin (8.3%) and nitrofurantoin (8.8%) resistance. Resistance to two or three of the first-line antibiotics—trimethoprim, cefalexin and nitrofurantoin—was 5.5% and 0.6%, respectively. In E. coli there was low fosfomycin resistance at 3.1%. In resistant isolates subject to extended sensitivity testing, moderate pivmecillinam (21%) resistance was demonstrated. Organisms demonstrating AmpC and ESBL resistance were detected in 3.2% and 3.5% of isolates. Trimethoprim resistance was highest at James Paget University Hospital (37%) and surrounding general practices (30%).

Conclusions

This study illustrates resistance rates to commonly prescribed antibiotics for urinary tract infections in Norfolk and Waveney. Adjustments to local empirical antibiotic guidelines have been shaped by the resistance rates demonstrated herein.
pyDeid: an improved, fast, flexible, and generalizable rule-based approach for deidentification of free-text medical records
Authors: Sundrelingam Vaakesan , Parimoo Shireen , Pogacar Frances , Koppula Radha , Shin Saeha , Pou-Prom Chloe , Roberts Surain B , Verma Amol A , Razak Fahad
Published: January 2025

Objectives

Deidentification of personally identifiable information in free-text clinical data is fundamental to making these data broadly available for research. However, there exist gaps in the deidentification landscape with regard to the functionality and flexibility of extant tools, as well as suboptimal tradeoffs between deidentification accuracy and speed. To address these gaps and tradeoffs, we develop a new Python-based deidentification software, pyDeid.

Materials and Methods

pyDeid uses a combination of regular expression-based rules, fixed exclusion lists and inclusion lists to deidentify free-text data. Additional configurations of pyDeid include optional named entity recognition and custom name lists. We measure its deidentification performance and speed on 700 admission notes from a Canadian hospital, the publicly available n2c2 benchmark dataset of American discharge notes, as well as a synthetic dataset of artificial intelligence (AI) generated admission notes. We also compare its performance with the Physionet De-identification Software and the popular open-source Philter tool.

Results

Different configurations of pyDeid outperformed other tools on various metrics, with a “best” accuracy value of 0.988, best precision of 0.889, best recall of 0.950, and best F1 score of 0.904. All configurations of pyDeid were significantly faster than Philter and Physionet De-identification Software, with the fastest deidentification speed of 0.48 s per note.

Discussion and Conclusions

pyDeid allows the flexibility to prioritize between performance and speed, as well as precision and recall, while addressing some of the gaps in functionality left by other tools. pyDeid is also generalizable to domains outside of clinical data and can be further customized for specific contexts or for particular workflows.
Accuracy of privacy preserving record linkage for real world data in the United States: a systemic review
Authors: Tyagi Khushi , Willis Sarah J
Published: January 2025

Objectives

Examine the accuracy of privacy preserving record linkage (PPRL) matches in real world data (RWD).

Materials and Methods

We conducted a systematic literature review to identify articles evaluating PPRL methods from January 1, 2013 to June 15, 2023. Eligible studies included original research reporting quantitative metrics such as precision and recall in health-related data sources. Covidence software was used to manage the review process.

Results

Five studies met our inclusion criteria. Tokenization and hash functions were used to hash and encrypt personally identifiable information (PII) including first and last names, dates of birth (DOB), and Social Security Numbers (SSNs) in a variety of RWD. All identified studies utilized deterministic matching. Combinations of tokenized or hashed PII that included “quasi-identifiers” like names and DOBs had consistently high precision (>95%) but lower recall, likely due to misspelled or inconsistently spelled names and name changes. SSN-based combinations demonstrated high precision but variable recall due to incomplete SSN data in RWD. Studies that employed algorithms in which at least one match was identified from a specified set of PII combinations provided high precision and high recall.

Discussion

The systematic review indicates that PPRL methods generally provide highly accurate patient data linkage while maintaining privacy.

Conclusions

Researchers should carefully consider the completeness and stability of each PII element selected for PPRL and may want to employ a strategy that allows for patient records to be matched if they meet at least one of several combinations of PII.