bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of archaeal pseudomurein biosynthesis genes through pangenomics
Authors: Lupo Valérian , Roomans Célyne , Royen Edmée , Ongena Loïc , Jacquemin Olivier , Mullender Coralie , Kerff Frédéric , Baurain Denis
Published: February 2025

The peptidoglycan (PG, or murein) is a mesh-like structure, which is made of glycan polymers connected by short peptides and surrounds the cell membrane of nearly all bacterial species. In contrast, there is no PG counterpart that would be universally found in Archaea but rather various polymers that are specific to some lineages. Methanopyrales and Methanobacteriales are two orders of Euryarchaeota that harbor pseudomurein (PM), a structural analog of the bacterial PG. Owing to the differences between PG and PM biosynthesis, some have argued that the origin of both polymers is not connected. However, recent studies have revealed that the genomes of PM-containing Archaea encode homologs of the bacterial genes involved in PG biosynthesis, even though neither their specific functions nor the relationships within the corresponding inter-domain phylogenies have been investigated so far. In this work, we devised a pangenomic bioinformatic pipeline to identify proteins for PM biosynthesis in Archaea without prior genetic knowledge. The taxonomic distribution and evolutionary relationships of the candidate proteins were studied in detail in Archaea and Bacteria through HMM sequence mining and phylogenetic inference of the Mur domain-containing family, the ATP-grasp superfamily, and the MraY-like family. Our results show that archaeal muramyl ligases are of bacterial origin but diversified through a mixture of horizontal gene transfers and gene duplications. However, in the ATP-grasp and MraY-like families, the archaeal members were not found to originate from Bacteria. Our pangenomic approach further identified five new genes potentially involved in PM synthesis and that would deserve functional characterization.

IMPORTANCE

Methanobrevibacter smithii
is an archaea commonly found in the human gut, but its presence alongside pathogenic bacteria during infections has led some researchers to consider it as an opportunistic pathogen. Fortunately, endoisopeptidases isolated from phages, such as PeiW and PeiP, can cleave the cell walls of
M. smithii
and other pseudomurein-containing archaea. However, additional research is required to identify effective anti-archaeal agents to combat these opportunistic microorganisms. A better understanding of the pseudomurein cell wall and its biosynthesis is necessary to achieve this goal. Our study sheds light on the origin of cell wall structures in those microorganisms, showing that the archaeal muramyl ligases responsible for its formation have bacterial origins. This discovery challenges the conventional view of the cell-wall architecture in the last archaeal common ancestor and shows that the distinction between “common origin” and “convergent evolution” can be blurred in some cases.
Gut commensal
Alistipes shahii
improves experimental colitis in mice with reduced intestinal epithelial damage and cytokine secretion
Authors: Lin Xiaoying , Xu Mingchao , Lan Ruiting , Hu Dalong , Zhang Suping , Zhang Shuwei , Lu Yao , Sun Hui , Yang Jing , Liu Liyun , Xu Jianguo
Published: February 2025

The commensal bacterium
Alistipes shahii
is a core microbe of the human gut microbiome and its abundance is negatively correlated with inflammatory bowel diseases (IBDs). However, its fundamental role in regulating inflammatory response remains unknown. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we examined the effect of
A. shahii
strain As360 intervention on host inflammatory response and found that
A. shahii
As360 alleviated disease activity index, colon shortening, and colonic histopathological lesion. The levels of tight junction proteins (mainly ZO1 and claudin-1) were decreased in DSS-induced colitis mice, whereas the levels of these proteins were elevated in colitis mice with
A. shahii
As360 treatment. In addition,
A. shahii
As360 treatment led to alterations in cytokine release, especially an increase of IL10. It also led to reduced expressions of
mtor
and
Nlrp3
and increased expression of mTOR inhibitor
Ddit4
at the transcriptional level. 16S rRNA amplicon sequencing found that
Bacteroides
, a producer of short-chain fatty acids (SCFAs), was enriched in the fecal samples of mice with
A. shahii
treatment. Metabolic analyses found that, following
A. shahii
As360 treatment, the SCFAs in the fecal content was increased whereas lactic acid was decreased in the cecal content. These findings suggest that supplementation with
A. shahii
As360 is a promising strategy to prevent colitis.

IMPORTANCE

As one of the core microbes and keystone species in the human gut,
Alistipes shahii
has the potential to inhibit inflammation and improve inflammatory bowel diseases (IBDs) conditions. In this study, we experimentally demonstrated that oral administration of
A. shahii
As360 alleviated symptoms of colitis, altered the release of cellular inflammatory factors, reduced the intestinal epithelial barrier damage, and changed gut microbiota and fecal metabolites. These findings provide a deeper understanding of the beneficial effects of
A. shahii
and its perspective for better strategies to prevent IBD.
Dissemination of
bla
NDM
-harboring plasmids in carbapenem-resistant and hypervirulent
Klebsiella pneumoniae
Authors: Gu Yihai , Wang Xiao , Zhang Wei , Weng Rui , Shi Qiucheng , Hou Xuan , Wang Hui , Deng Minghui , Mou Jian , Jiang Yan
Published: February 2025

Carbapenem-resistant
Klebsiella pneumoniae
(CRKP) is a global public health threat, and CRKP strains carrying
bla
NDM
plasmids are of particular concern. Here, the antimicrobial resistance and molecular epidemiological characteristics of 59 CRKP strains isolated from patients receiving care at a tertiary hospital in China from 2019 to 2021 were determined through antimicrobial resistance testing and genomic sequence analysis. We analyzed the genetic characteristics and transmissibility of
bla
NDM
-harboring plasmids through S1-digested pulsed field gel electrophoresis, Southern blotting, and conjugation assays. The virulence levels of the strains were evaluated using a
Galleria mellonella
larvae infection model. All the CRKP strains were multidrug resistant, but none were resistant to colistin or tigecycline. A total of eight sequence types (STs) were detected in these CRKPs, with ST11 (39/59) and ST15 (12/59) being the most common. Among the carbapenemase genes,
bla
KPC
(39/59) and
bla
NDM
(18/59) were the most common, with
bla
KPC-2
transmitted mainly through ST11 clones and
bla
NDM-5
transmitted through ST15 clones. The
bla
NDM
-harboring plasmids primarily belong to the incompatibility type IncX3 (14/18). IS
26
-mediated gene recombination, sequence insertion, and plasmid integration were observed to occur during the dissemination process. The resistance gene profile mediated by
bla
NDM
-harboring plasmids can be transferred through conjugation, which have almost no fitness cost and is extremely stable after passage. Six of these strains presented carbapenem resistance combined with hypervirulence (CR-hvKP), including ST23-KL1, ST218-KL57, ST17-KL112, and ST147-KL64. Additionally,
bla
NDM
-harboring plasmids can disseminate rapidly over large surface areas and persist for a long time in medical institutions, leading to outbreaks of highly resistant clones associated with CR-hvKP.

IMPORTANCE

The appearance of plasmids carrying
bla
NDM
and the rise of carbapenem-resistant hypervirulent
Klebsiella pneumoniae
(CR-hvKP) have significantly escalated the public health risk associated with Carbapenem-resistant
Klebsiella pneumoniae
(CRKP). In this study, we described the resistance rates, virulence factors, and molecular epidemiology of 59 CRKP isolated from patients at a tertiary hospital in China from 2019 to 2021. Beyond this, we also assessed the characteristics of
bla
NDM
-harboring plasmids and their dissemination patterns among CRKP, especially some CR-hvKP. Our research contributes to the field of
bla
NDM
dissemination studies, prompting researchers to formulate strict measures to prevent and control the development of
bla
NDM
-harboring plasmids, which is instrumental in the clinical development of targeted treatment plans.
Chemical and isotopic fractionation during melt inclusion formation
Authors: da Silva Ricardo Bruna , Oeser Martin , Lynn Kendra J. , Bennett Neil R. , Chu Xu , Henderson Grant , Liu Yanan , Weyer Stefan , Sio Corliss K.
Published: February 2025

Melt inclusions are used to study the origin and evolution of magmas. The extent to which they represent equilibrium melt compositions, however, critically hinges on the ratio of crystal growth rate to diffusion rate in melts. If the rate of crystal growth is limited by the supply of nutrients and the dissipation of unwanted components, the trapped melt will be depleted in compatible elements and enriched in incompatible elements. Despite widespread recognition of the potential for melt inclusions to trap disequilibrium compositions, their identification remains a challenge. Here, we demonstrate how stable isotopes provide a solution to this problem. Melt inclusions in basaltic tephra from Kīlauea volcano, Hawai‘i, display Mg isotope fractionation up to 0.49‰ (26Mg/24Mg) relative to bulk rock. These observations indicate that kinetic processes, such as chemical diffusion, are at play, as equilibrium mineral-melt isotope fractionation at high temperatures is an order of magnitude smaller. We propose that the heavy Mg isotopic compositions of the melt inclusions were generated by the faster diffusion and thus preferential incorporation of 24Mg by the growing olivine, leaving the slower diffusant (26Mg) behind. The incompatible elements (e.g., Ca, Ti, and K) are predicted to display similarly large fractionations when boundary layer effects are significant. These findings show that stable isotopes can be a useful tool in identifying disequilibrium compositions in melt inclusions.
Supplemental Material: Salinic thrust panels, mélanges, and folds with superimposed Acadian oblique cleavage-fold relationships in accreted Ordovician oceanic rocks of the Fournier Supergroup and Silurian synorogenic cover rocks in northern New Brunswick, Canada
Authors: Staal C.R. van , al. et
Published: February 2025

Figure S1: Modelled N-S profiles of aeromagnetic anomalies associated with the Devereaux Complex.
Thyroid storm: hyperemesis and second trimester miscarriage
Authors: Alim Melissa , Teo Zhen Quan , Lovell Rosemary
Published: February 2025

Thyroid storm is a rare and life-threatening endocrine emergency. This complication is typically seen in women with a history of thyroid disorders triggered by a stressor such as surgery, trauma or severe illness. In pregnancy, there is significant fetal morbidity including preterm birth or fetal death. We present a case of thyroid storm in the second trimester precipitated by hyperemesis gravidarum and gestational transient thyrotoxicosis which was complicated by maternal collapse, miscarriage and cardiomyopathy.
Equitable access to quality trauma systems in Ghana: a qualitative study
Authors: Kunfah Sheba Mary Pognaa , Yakubu Mustapha , Ofori-Appiah Bernard , Ayingayure Emmanuel , Odland Maria Lisa , Yempabe Tolgou , Buunaaim Alexis Dun Bo-ib , Konadu-Yeboah Dominic , Ignatowicz Agnieszka , Davies Justine , Stephen Tabiri
Published: February 2025

Objectives

To explore the barriers to accessing quality trauma care after injury in Ghana.

Design

A qualitative study using semi-structured interviews and focus group discussions in one rural and one urban setting. Interviews and focus group discussions were audio recorded, transcribed and thematically analysed using the four-delay framework.

Participants

53 patient participants (n=39 men, n=14 women, mean age=41, SD=15.6, n=38 rural participants, n=15 urban participants) who had an injury not more than 6 months preceding the start of the study.

Settings

15 individual interviews (n=15) and 2 focus group discussions (n=23) were conducted in Yendi (rural setting in Ghana) and 10 individual interviews (n=10) and 1 focus group discussion (n=5) in the Tamale metropolis (urban setting in Ghana).

Results

Our findings showed that when an injury occurred, participants faced multiple barriers across all delays which prevented them from accessing quality injury care. Barriers were a mix of individual, community-level and health-system factors that were interrelated in many ways. Financial difficulties were one of the prominent barriers mentioned by the participants in both settings.

Conclusion

This study shows that multiple factors cause an injured patient to delay in seeking care, reaching care, receiving care and remaining in care. Therefore, there is a pressing need for comprehensive, community-driven strategies to strengthen health literacy at the community level. There is also a need for facility-based strategies that would improve the availability of medical and human resources to augment access to quality trauma care. Additionally, if policymakers focus on removing financial barriers to trauma care and strengthening referral systems, especially in the remote and rural areas, it would greatly improve access to quality trauma care in Ghana.
HPV vaccination among young adults in Switzerland: a cross-sectional study
Authors: El-Hadad Samia , Sachs Maike Katja , Barrense-Dias Yara , Granell Joan Carles Suris , Niggli Angela , Leeners Brigitte
Published: February 2025

Objective

This study aimed to evaluate the human papillomavirus (HPV) vaccination status among a representative sample of young adults (YAs) with a special focus on the catch-up vaccination uptake among the male population in Switzerland.

Design and setting

Data were extracted from an online self-administered questionnaire survey, conducted as a representative cross-sectional study in 2017. To understand correlations between vaccination uptake and sociodemographic characteristics, sexual health, and sexual behaviour, we performed bivariate analysis and multivariate regression analysis.

Participants

Out of a total of 7142 participants, 2155 female and 996 male cisgender participants remained for statistical evaluation after excluding homosexual/bisexual study participants, those with gender dysphoria or those without knowledge of their vaccination status.

Outcomes

The primary outcome of this study was to investigate HPV vaccination rates among female and male YAs in Switzerland. As secondary outcomes, we assessed uptake of catch-up vaccination and identified key factors influencing HPV vaccination uptake.

Results

Vaccination rates were significantly higher in the female group (40.9%), while not wanting to be vaccinated and doubting benefits and necessity of the vaccine were main reasons for non-vaccination. Vaccination coverage among male YAs was very low (7.8%), primarily due to insufficient information. Parents not being Swiss-born, a higher family socioeconomic status and having had a gynaecological visit at a younger age correlated with HPV vaccination uptake for female YAs. In the male group, participants with a higher number of lifetime partners and a younger age at first steady partnership were more likely to report a positive vaccination status. Knowledge about the benefits of catch-up vaccination was very limited among both genders.

Conclusions

The lack of knowledge about benefits of HPV vaccination contributes to low vaccine uptake, especially occurring among the male population, must be addressed. Given the number of people who reported not knowing whether they were vaccinated or not, it is crucial to ensure that there is a thorough discussion about HPV and the protection the vaccine provides when presenting for vaccination.
Cirrhosis and Faecal microbiota Transplantation (ChiFT) protocol: a Danish multicentre, randomised, placebo-controlled trial in patients with decompensated liver cirrhosis
Authors: Støy Sidsel , Eriksen Lotte Lindgreen , Lauszus Johanne Sloth , Damsholt Søren , Baunwall Simon Mark Dahl , Erikstrup Christian , Vilstrup Hendrik , Jepsen Peter , Hvas Christian , Thomsen Karen Louise
Published: February 2025

Introduction

Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.

Methods and analysis

In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score≤12 will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function.

Ethics and dissemination

The Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results.

Trial registration number

ClinicalTrials.gov study identifierNCT04932577.
Daily SARS-CoV-2 testing after travel-related close contact notifications during elite sporting events hosted in the UK: a longitudinal study
Authors: Davies Madeleine , Hill Jerry , Goggins Luke , Peirce Nicholas , Smith Jenifer , Boulter Matthew , Fowler Tom Alan , Buchan Iain , Calder James D F
Published: February 2025

Isolation requirements for COVID-19 close contacts risked discouraging elite athletes and support staff from travelling to international sports events hosted in the UK during 2021.

Objectives

The purpose of this study, in collaboration with the UK Health Security Agency, was to develop and implement a risk assessment and workplace daily testing approach in elite sporting events, for individuals who would otherwise be excluded by quarantine.

Methods

Longitudinal study of athletes and staff identified as close contacts during travel (ie, flights, train) to specific international sports events. A risk assessment was undertaken, and participants were categorised as at ‘low’ or ‘high’ risk of developing SARS-CoV-2 based on their exposure circumstances. High-risk individuals remained in 10-day isolation, whereas those of low risk underwent daily symptom and lateral flow testing, enhanced workplace mitigation and selected work activities were permitted.

Results

Of 29 514 event personnel, 202 travel-related close contacts were reported to the study team, of which 126 were eligible from 40 events in 7 sports. Of the individuals assessed, 105 (83.3%) were classified as low risk, while 21 (16.7%) were classified as high risk. No low-risk individuals tested positive in over 280 rapid antigen tests.

Conclusion

International sports events rely on athlete and support staff availability, with economic consequences of event cancellation or postponement. Our study showed no detection of SARS-CoV-2 in low-risk close contacts, and enabled their sustained participation. This multidisciplinary intervention appears to have been effective, enabling large-scale event continuation, while minimising risk to athletes, employees and the wider public.
Advancing clinical management of left ventricular thrombosis: prevention, detection and treatment modalities in the modern era
Authors: Zhang Qian , Zheng Haikuo , Zhang Zhongfan , Xu Yuanzhen , Zhang Wenqi
Published: February 2025

Heightened interest in left ventricular thrombus (LVT) stems from the consistent association of subsequent stroke and systemic embolism after LVT, and many aspects of its management still exist in a grey area of evidence. The current delay in intervention is likely related to a limited understanding of the disease pathophysiology, along with an underestimation of LVT by standard imaging modalities. With the rapid development of antithrombotic regimens consisting of direct oral anticoagulants (OACs), which have shown early safety and efficacy, there is a growing need to understand and accurately diagnose the LVT process in order to determine appropriate management solutions. This educational review will oversee LVT pathophysiology, current status of the guidelines-recommended echocardiographic approach and the role of multimodality imaging, as well as prevention and treatment modalities in the modern era. Meanwhile, the review proposes an algorithm for the prevention and treatment of LVT based on current guidelines and expert consensus, and highlights the need for more investigations to identify risk stratification methods for individual patients, and lastly, discusses the potential of direct OACs in the management of LVT.
Updated evidence on selection and implementation of an invasive treatment strategy for older patients with non-ST-segment elevation myocardial infarction
Authors: Gill Kieran , Kunadian Vijay
Published: February 2025

Non-ST-segment elevation myocardial infarction (NSTEMI) is the most common acute coronary syndrome diagnosis in older patients. In the UK, there are ~20 000 NSTEMI cases annually in patients aged ≥75 years. Despite therapeutic advances in pharmacological and invasive management, studies show that older patients with NSTEMI experience worse in-hospital and long-term outcomes than younger patients, suggesting a clear need for robust evidence in this cohort.

The European Society of Cardiology guidelines recommend that invasive management should be considered holistically with no specified age cut-offs. However, older patients are less likely to receive invasive management due to a paucity of evidence from trials that represent contemporary clinical characteristics of older adults. Recruiting older patients realistic of those encountered in clinical practice is hugely challenging. Chronological age alone does not reflect the heterogeneity of the older population; ~30% of older patients with NSTEMI are frail, ~65% are cognitively impaired and most live with at least two additional comorbidities that can influence risk. Weighing the risk of an NSTEMI in an older adult against competing risks attributable to underlying frailty, comorbidities and cognitive impairment poses a key challenge.

Recently, the SENIOR-RITA trial showed that invasive management in older patients with NSTEMI is safe and reduces non-fatal myocardial infarction and subsequent revascularisation but does not improve mortality. Individualised risk assessment and shared decision-making is necessary to guide these nuanced decisions. This review discusses the latest evidence regarding invasive management in the older population with NSTEMI, including the impact of geriatric syndromes on clinical outcomes.
Assessment of neuronal and glial serum biomarkers in myelin oligodendrocyte glycoprotein antibody-associated disease: the MULTIMOGAD study
Authors: Marignier Romain , Villacieros-Álvarez Javier , Espejo Carmen , Arrambide Georgin , Fissolo Nicolás , Gutiérrez Lucía , Dinoto Alessandro , Mulero Patricia , Rubio-Flores Laura , Nieto Pablo , Alcalá Carmen , Meca-Lallana Jose E , Martínez-Garcia Pedro , Millán Jorge , Bernard-Valnet Raphaël , González Inés , Orvíz García Aida , Tellez Raquel , Navarro Laura , Presas-Rodríguez Silvia , Romero-Pinel Lucía , Martínez-Yélamos Sergio , Cuello Juan Pablo , Alonso Torres Ana Maria , Piñar Raquel , Álvarez Bravo Gary , Benyahya Lakhdar , Trouillet-Assant Sophie , Dyon-Tafani Virginie , Froment Tilikete Caroline , Ruet Aurelie , Bourre Bertrand , Deschamps Romain , Papeix Caroline , Maillart Elisabeth , Kerschen Philippe , Ayrignac Xavier , Rovira Alex , Auger Cristina , Audoin Bertrand , Montalban Xavier , Tintore Mar , Mariotto Sara , Cobo-Calvo Alvaro
Published: February 2025

Background

Serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) have emerged as important biomarkers in multiple sclerosis (MS) and aquaporin-4 seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD). However, their interest in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear. Our aim was to characterise sNfL and sGFAP profile and analyse their usefulness in predicting relapses and disability in MOGAD.

Methods

Retrospective study of adult MOGAD patients with serum samples collected at baseline (≤3 months from disease onset) and follow-up (>6 months from baseline sample). sNfL and sGFAP were analysed using Simoa HD-1, and values were compared across time-points. The association between biomarkers and clinical variables and their predictive value for disability and relapses were analysed.

Results

Eighty-nine MOGAD patients were included. Baseline sNfL and sGFAP values were high at baseline and decreased over time (p<0.001, p=0.027, respectively). sNfL and sGFAP values were associated with Expanded Disability Status Scale (EDSS) at attacks (β 0.15 (0.06; 0.25), p=0.002; β 0.14 (0.07; 0.21), p<0.001, respectively) and were lower in optic neuritis presentations (β −0.69 (−1.18; −0.19), p=0.007; β −0.42 (−0.76; −0.08), p=0.016). Biomarker deltas[Δ] (baseline values – second samples values) were associated with ΔEDSS (initial EDSS - final EDSS) (ΔsNfL β 0.52 (0.01; 1.04), p=0.046; ΔsGFAP β 1.07 (0.38; 1.75), p=0.003). Finally, sNfL values independently predicted the risk of relapses (HR 2.06 (1.41; 3.01), p<0.001).

Conclusions

Our results on sNfL and sGFAP suggest initial neuro-axonal and astrocytic damage in MOGAD and the utility of these biomarkers at onset and follow-up in predicting clinical recovery and relapses.
Clinical-radiological presentation and natural history of iatrogenic cerebral amyloid angiopathy
Authors: Fandler-Höfler Simon , Kaushik Kanishk , Storti Benedetta , Pikija Slaven , Mallon Dermot , Ambler Gareth , Damavandi Payam Tabaee , Panteleienko Larysa , Canavero Isabella , van Walderveen Marianne A A , van Etten Ellis S , DiFrancesco Jacopo Cosimo , Enzinger Christian , Gattringer Thomas , Bersano Anna , Wermer Marieke J H , Banerjee Gargi , Werring David J
Published: February 2025

Background

We aimed to describe neuroimaging features, clinical profiles and long-term outcomes in patients with iatrogenic cerebral amyloid angiopathy (iCAA).

Methods

We performed a systematic literature search for case series of iCAA and included individual patients and their longitudinal clinical and neuroimaging data in this pooled cohort study. Patients meeting a modified version of the Queen Square criteria for iCAA were included. Baseline and follow-up MRIs were centrally analysed for markers of CAA using validated rating scales.

Results

We included 51 patients (68.6% male, median age at presentation 48 years), 51.0% with probable and 49.0% with possible iCAA. We evaluated 219 MRIs acquired over a median follow-up time of 3.7 years (IQR 1.8–6.4). There were 43 symptomatic intracerebral haemorrhages (ICH) in 24 patients during follow-up, a rate of 16.7 per 100 patient-years.

Patients with previous supratentorial brain surgery had an ipsilateral-dominant distribution and spread of haemorrhagic markers on MRI. 14/51 (27.5%) patients had transient inflammatory changes (cortical or parenchymal oedema, sulcal hyperintensities). Haemorrhagic markers progressed during follow-up. In addition to 43 symptomatic ICH, 36 asymptomatic ICH (mostly smaller intragyral haemorrhages) were detected on follow-up scans. Besides numerous lobar microbleeds (median 16 at baseline, 53 at last follow-up), deep microbleeds were present in 19.6% of patients at baseline and 44.4% at follow-up. Severe perivascular spaces in centrum semiovale were common at baseline (64.7%) and follow-up (95.6%).

Conclusions

Patients with iCAA appear to have distinctive MRI characteristics, which might differentiate iCAA from other CAA subtypes and provide new insights into underlying disease mechanisms.
Observational study of changes to glucocorticosteroid prescribing patterns in duchenne muscular dystrophy in the UK over the last decade
Authors: Landon Gregory , Stimpson Georgia , Guglieri Michela , Sarkozy Anna , Manzur Adnan Y ,   UK NorthStar Clinical Network, Muntoni Francesco , Baranello Giovanni
Published: February 2025

Background

Glucocorticosteroids (GC) are standard-of-care treatment for most boys with duchenne muscular dystrophy (DMD). GC use has changed over time with evolving evidence, and we describe GC patterns, dosing and side-effects in the UK over 11 years.

Method

NorthStar data from 2012 to 2022 were analysed to understand GC type, regime and starting age. GC dose with age, patterns of GC switching and side-effect profiles by type and regime were also analysed. Participants attributed to ‘other’ regimes were queried and details were included.

Results

Data on GC usage were available for 1117 boys, across 6905 observations, with 74% of boys GC treated. Prednisolone was the most common regime in the period (65% of assessments) but deflazacort prescription has increased (17% in 2012 and 43% in 2022). Daily regimes were more common (66% of assessments), and the incidence of intermittent (10 days on/10 days off) regimes has declined (46% in 2012 and 26% in 2022). Older participants were more commonly on less than recommended doses, and this was more common in those on deflazacort or daily regimes. Gastrointestinal symptoms and cushingoid features were more common in those on deflazacort than prednisolone, while increased appetite, cushingoid features, gastrointestinal symptoms and insomnia were more common in those on daily than intermittent regimes.

Conclusions

The use of deflazacort and daily regimes has steadily increased across the UK North Star Network in the last decade. This study provides one of the largest up-to-date real-world set of data of evolution in prescription patterns and the occurrence of side-effects in different groups of GC-treated DMD.
Hoover’s sign is a sign of functional weakness: or is it more?
Authors: Coebergh Jan
Published: February 2025

Hoover’s sign has long been used to support a clinical diagnosis of functional weakness. However, it also occurs in people with pain, other functional disorders and functional neurological disorder without weakness. Some of its clinical characteristics, such as being more prominent with visual attention, suggest it might be reframed as a sign of agency. The experience, reflections and awareness of people with an abnormal Hoover’s sign can be seen in this context. Reframing Hoover’s sign by linking it to agency, and extending it to other clinical scenarios, could help clinicians and, most importantly, patients.

Hoover’s sign has long been used to support a clinical diagnosis of functional weakness. This does not explain why it can be found in pain, other functional disorders and functional neurological disorder without weakness. It can be reframed as a sign of agency by looking at clinical nuggets like Hoover’s in structural changes in the brain and other disorders and clinical characteristics, like it being more prominent with visual attention. The clinical experience of people with an abnormal Hoover’s sign and their reflections and awareness can be seen in this context.

A recently discovered clinical technique of inducing it briefly in healthy people with pressure on the patella or tonic vibration is discussed. This illustrates the importance of sensory processing (especially sensory attenuation and proprioception) and learning/habituation to stimuli, which is known to be altered in functional neurological disorder and other functional disorders.

Reframing Hoover’s sign by linking it to agency and extending it to other clinical scenarios could help clinicians, neuroscience and, most importantly, patients.
Adult polyglucosan body disease: ultrarare but commonly misdiagnosed
Authors: Caiza-Zambrano Francisco , Aldecoa Mayra , Rugilo Carlos , Taratuto Ana Lia , Marchesoni Cintia , León-Cejas Luciana , Reisin Ricardo , Bonardo Pablo
Published: February 2025

Adult polyglucosan body disease is a rare genetic condition caused by biallelic pathogenic variants inGBE-1gene. Affected patients typically have urinary dysfunction, progressive gait disturbance and cognitive impairment. We report a 63-year-old woman with urinary incontinence, walking difficulty and episodes of forgetfulness. She had symmetrical limb weakness with upper motor neurone signs, distal sensory loss and a broad-based ataxic gait. MR scans of the brain and spine showed white matter changes with cerebellar and spinal cord atrophy. Sural nerve biopsy identified intra-axonal polyglucosan bodies. A multigene panel test identified aGBE-1pathogenic variant, confirming the diagnosis of adult polyglucosan body disease. This case emphasises the importance of considering rare genetic disorders in people with autonomic dysfunction, mixed upper and lower motor neurone signs, peripheral neuropathy and cognitive impairment.
HIV-related microaggressions and depressive symptoms among people living with HIV: the mediating roles of internalised stigma and coping with shame
Authors: Taşlıoğlu Sayıner Aliye Canan , Turan Bulent , Nazlı Arzu , Özer Deniz , Abdollahpour Ranjbar Hamed , Nemli Salih Atakan , Ghaffari Ahmad Nejat , Mert Vahabi Merve , Ayhan Nur Miray , Gokengin Deniz , Norcini Pala Andrea
Published: February 2025

Objectives

Overtly experienced HIV-related stigma is associated with depressive symptoms for people living with HIV (PLWH). Research suggests that an important mediating mechanism in this association is internalised stigma, where PLWH accept negative societal views about HIV, apply them to themselves and develop a negative view of themselves. Microaggressions are subtle and indirect discriminatory behaviours and, like overtly experienced stigma, may also contribute to depressive symptoms. We tested this hypothesis and examined the mediating roles of internalised stigma and maladaptive ways of coping with shame in the association between microaggressions and depressive symptoms among PLWH in Türkiye.

Methods

This study examines the serial mediating roles of internalised HIV stigma and shame-related coping strategies (ie, withdrawal and self-attack) in the association between HIV-related microaggressions and depressive symptoms among PLWH. PLWH in Izmir, Türkiye (N=308) completed validated scales measuring experiences of microaggressions, internalised HIV stigma, coping strategies related to shame and depression symptoms.

Results

Structural equation modelling results suggest that internalised HIV stigma significantly mediates the relationship between HIV-related microaggressions and depression symptoms. Furthermore, serial mediation analysis suggests that withdrawal and self-attack strategies of coping with shame mediate the association between internalised HIV stigma and depressive symptoms. Thus, internalised HIV stigma and shame-related coping strategies may partially stem from experiencing HIV-related microaggressions and may negatively affect the mental health of PLWH.

Conclusions

Findings highlight the importance of assessing subtle forms of discrimination (ie, microaggressions) given their negative impact on the self-concept of PLWH. In addition to addressing negative attitudes and behaviours against PLWH in society, interventions that help PLWH cope with shame-related experiences might improve their mental health.
Distress thermometer problem list and distress and depression in psycho-oncology
Authors: Wallace Lyndsey , Banerjee Anjishnu , Molinaro Jessica , Murray Julie , Danhieux-Poole Carrie , Uselmann Ann Marie , Knight Jennifer M.
Published: February 2025

Purpose

This study examines the relationship between specific problem categories endorsed by patients with cancer seeking psycho-oncology services and their levels of distress and depression. Additionally, we investigate the potential associations between demographic and clinical characteristics and the endorsement of specific problem categories.

Methods

A non-randomised interventional study was conducted with adult patients referred for psycho-oncology services. Patients attended 1–2 psycho-oncology sessions, completing the distress thermometer, problem checklist and Patient Health Questionnaire at the start of each visit and repeated the distress thermometer at visit end. Analyses evaluated the associations between problem checklist categories and levels of distress and depression.

Results

Patients who endorsed a higher problem load, regardless of problem category, endorsed higher levels of distress and depression. Notably, younger patients, non-white patients and patients with breast cancer endorsed higher problem loads.

Conclusion

The findings emphasise the importance of addressing problem load as a contributor to distress and depression among patients with cancer. While problem load was associated with patient characteristics, further investigation is needed to understand how these characteristics may influence distress and depression directly. Interventions should focus on reducing problem load to improve psychological well-being.
Getting Back in the Black: An Interactive Decision-Support Tool to Aid Timely Management Decisions Associated with Alaskan Black Cod (Sablefish) Discarding
Authors: Goethel Daniel R. , Williams Benjamin C , Cleaver Sara M. , Lunsford Chris CR
Published: February 2025

Fisheries management decisions often depend on complex modeling, but conveying results in non-technical terms can be challenging for scientists lacking formal communication training. As co-management gains traction, it is imperative that scientists develop less esoteric methods to convey results in broadly accessible formats. Online tools are appealing because interactive applications align with many stakeholders' digital comfort zone and programming in R is a common skillset among fisheries scientists. We developed an online decision support tool to address a time-sensitive management issue (allowing discards of small, low-value fish) within the Alaska sablefish fixed-gear fishery. Based on catch projection models, discarding due to the proposed de facto minimum size limit (22 inches) were shown to have minimal impacts on the resource or revenue. Pairing a technical document with an interactive application helped convey results and may have improved understanding and transparency of a complex analysis. The sablefish example underscores the need for a paradigm shift from technocratic approaches to more interactive and accessible methods for conveying scientific results at the science-policy interface.
Non-geodesic timelike observers and the ultralocal limit
Authors: Saadati Reza , Valsan Luca , Faraoni Valerio
Published: February 2025

The ultralocal limit along timelike geodesics, in which any geometry reduces to Bianchi I, does not extend to non-geodesic timelike observers. Exceptions are discussed, including particles with variable mass, test particles in Einstein frame scalar-tensor gravity, and self-interacting dark matter.
Personalized Learning Resource Recommendation Text Emotion Recognition Method Based on Deep Transfer Learning
Authors: Li Shuo , Han Ting
Published: February 2025

In the process of personalized learning resource recommendation, recommendation systems usually combine text data related to the resources themselves with text data related to learners. They analyze learners’ learning needs, interests, and preferences through algorithms. Then they select learning resources that meet learners’ needs from the learning resource library for recommendation. In order to achieve accurate and effective recognition of text emotions in personalized learning resource recommendations, a text emotion recognition method based on deep transfer learning is proposed. Based on the control value theory and the emotional attribute induction method, we will construct a recommended text emotional attribute index system which includes the text emotional attributes type level. For example, we collect multiple text data containing all emotional attributes. Then, we reconstruct the text data set through data cleaning, text analysis, and stop-word removal operations. Furthermore, we extract deep text features based on convolutional neural networks (CNNs). Finally, we integrate deep transfer learning methods to achieve sentiment classification and recognition of recommended text. The experimental results show that the recognition rates of positive and negative emotions in the source target domain text obtained by the design method are 93.5% and 98.2%, respectively; 98.9% and 96.2%, respectively. The mean square error of obtaining emotion recognition results is less than 0.1. This indicates that the knowledge learned from the source data in the design method can be well applied to the target data of personalized learning resource recommendation text. Therefore, it can effectively improve the generalization ability of low-resource datasets. Moreover, it can make reasonable emotional judgments on personalized learning resource recommendation text.
The Coupling Relationship Between Flexible Governance and Public Emotion from the Perspective of Systems Science and Computational Intelligence
Authors: Lin Youchang , Cui Li , He Tingting , Wu Xiling
Published: February 2025

As computational intelligence and the social economy evolve, as do public living standards, society wants a better quality of life that includes material and emotional well-being. Despite this increased knowledge, the public sector has often disregarded the importance of popular sentiment, which is important to national governance. Flexible governance, a strategic extension of management theory, and rationality-based modern government practices can address this oversight. A more flexible management style can improve public mood and social cohesion by promoting emotional public interaction and community governance. Flexible governance and public emotion within social growth constitute a dynamic coupling system that influences and guides each other within their boundaries. This nonlinear, non-equilibrium, two-way coupling system adapts to changing situations and realizes the full potential of flexible governance. The public sector must embrace this new paradigm and acknowledge the need for flexible governance to foster favorable public sentiment as it navigates modern governance difficulties. This study also supports the knowledge economy by acknowledging public sentiment’s intangible assets and their role in social progress. This research helps us comprehend economic development and governance efficacy in the knowledge-driven era by including emotional well-being in economic measurements.
lymph
: discontinuous poLYtopal methods for Multi-PHysics differential problems
Authors: Antonietti Paola F. , Bonetti Stefano , Botti Michele , Corti Mattia , Fumagalli Ivan , Mazzieri Ilario
Published: February 2025

We present the library
lymph
for the finite element numerical discretization of coupled multi-physics problems.
lymph
is a Matlab library for the discretization of partial differential equations based on high-order discontinuous Galerkin methods on polytopal grids (PolyDG) for spatial discretization coupled with suitable finite-difference time marching schemes. The objective of the paper is to introduce the library by describing it in terms of installation, input/output data, and code structure, highlighting – when necessary – key implementation aspects related to the method. A user guide, proceeding step-by-step in the implementation and solution of a Poisson problem, is also provided. In the last part of the paper, we show the results obtained for several differential problems, namely the Poisson problem, the heat equation, the elastodynamics system, and a multiphysics problem coupling poroelasticity and acoustic equations. Through these examples, we show the convergence properties and highlight some of the main features of the proposed method, i.e. geometric flexibility, high-order accuracy, and robustness with respect to heterogeneous physical parameters.
Challenges for Responsible AI Design and Workflow Integration in Healthcare: A Case Study of Automatic Feeding Tube Qualification in Radiology
Authors: Thieme Anja , Rajamohan Abhijith , Cooper Benjamin , Groombridge Heather , Simister Robert , Wong Barney , Woznitza Nicholas , Pinnock Mark A. , Wetscherek Maria T. , Morrison Cecily , Richardson Hannah , Pérez-García Fernando , Hyland Stephanie L. , Bannur Shruthi , Castro Daniel C. , Bouzid Kenza , Schwaighofer Anton , Ranjit Mercy P. , Sharma Harshita , Lungren Matthew P. , Oktay Ozan , Alvarez-Valle Javier , Nori Aditya , Harris Stephen , Jacob Joseph
Published: February 2025

Nasogastric tubes (NGTs) are feeding tubes that are inserted through the nose into the stomach to deliver nutrition or medication. If not placed correctly, they can cause serious harm, even death to patients. Recent AI developments demonstrate the feasibility of robustly detecting NGT placement from Chest X-ray images to reduce risks of sub-optimally or critically placed NGTs being missed or delayed in their detection, but gaps remain in clinical practice integration. In this study, we present a human-centered approach to the problem and describe insights derived following contextual inquiry and in-depth interviews with 15 clinical stakeholders. The interviews helped understand challenges in existing workflows, and how best to align technical capabilities with user needs and expectations. We discovered the trade-offs and complexities that need consideration when choosing suitable workflow stages, target users, and design configurations for different AI proposals. We explored how to balance AI benefits and risks for healthcare staff and patients within broader organizational, technical, and medical-legal constraints. We also identified data issues related to edge cases and data biases that affect model training and evaluation; how data documentation practices influence data preparation and labelling; and how to measure relevant AI outcomes reliably in future evaluations. We discuss how our work informs design and development of AI applications that are clinically useful, ethical, and acceptable in real-world healthcare services.
Exercise alters molecular profiles of inflammation and substrate metabolism in human white adipose tissue
Authors: Pino Maria F. , Dijkstra Pieter , Whytock Katie L , Ahn Cheehoon , Yu Gongxin , Sanford James A. , Hansen Josh , Hutchinson Chelsea , Gritsenko Marina A. , Piehowski Paul D. , Adkins Joshua N. , Carnero Elvis A. , Sealfon Stuart C. , Zaslavsky Elena , Nair Venugopalan , Smith Steven R. , Sparks Lauren M.
Published: February 2025

White adipose tissue (WAT) plays a significant role in whole-body energy homeostasis, and its excess typifies obesity. In addition to WAT quantity, perturbations in the basic cellular processes of WAT (i.e. quality) are also associated with obesity and metabolic disease. Exercise training alleviates metabolic perturbations associated with obesity; however, the underlying molecular mechanisms that drive these metabolic adaptations in WAT are not well described. Abdominal subcutaneous WAT biopsies were collected after an acute bout of exercise (1 day after) at baseline and following three weeks of supervised aerobic training in sedentary overweight women ( n = 6) without alterations in body weight and fat mass. RNA-seq, global proteomics, and phosphoproteomics in WAT revealed training-induced changes in 1527 transcripts, 154 proteins, and 144 phosphosites, respectively. Training decreased abundance of transcripts and proteins involved in inflammation and components of the extracellular matrix (ECM) and increased abundance of transcripts and proteins related with fatty acid esterification and lipolysis. In summary, short-term aerobic training significantly reduces local inflammation and increases lipid metabolism in WAT of sedentary overweight women - independent of alterations in body and fat mass. As such, some of the health benefits of aerobic training may occur through molecular alterations in WAT (i.e. enhanced quality) rather than a sheer reduction in WAT quantity.