Body composition (skeletal muscle, adipose tissue, and bone) is a general measure of health that can be determined from abdominal computed tomography (CT) using deep learning (DL) algorithms. Use of a volumetric approach, rather than the more commonly used single axial slice, likely improves the reliability and validity of body composition biomarkers, but a standardized approach is needed. A study was designed to test the reliability of volumetric body composition assessment in serial CTs. Residents of Southern Minnesota and Western Wisconsin who had two consecutive abdominal CT exams 1 to 14 days apart from 2010 to 2021 were identified. Previously-validated DL models were applied to both CT exams, and three methods of determining body composition biomarkers were compared: two-dimensional (2D) model on a slice at the midpoint of L3, three-dimensional (3D) model on a slice at the midpoint of L3, and 3D model on slices extending from L2 to L4. For each method, reliability was assessed by the intraclass correlation coefficient (ICC) separately in paired noncontrast and paired contrast-enhanced CT exams and validity was assessed by the strength of association of each body composition measure with age. There were 3,376 persons with paired noncontrast and 9,103 persons with paired contrast-enhanced CT exams. The 3D body composition biomarkers from L2-L4 showed generally better reliability than the 2D or 3D biomarkers at the midpoint of L3 with higher ICCs observed with or without use of contrast. The 3D body composition more strongly correlated with age than 2D body composition for most biomarkers. The 3D bone area from L2-L4 more strongly correlated with age than 3D bone area at the midpoint of L3. Volumetric L2-L4 body composition analysis shows better reliability and validity than single slice L3 analysis, and this may result in more accurate clinical associations with body composition.
Anastomotic leakage remains a major complication in colorectal surgery. Indocyanine green (ICG) fluorescence and flexible endoscopy (FE) are used to assess perfusion and anastomotic integrity. We aimed to evaluate global practice patterns and intersurgeon variability to inform structured recommendations. This international survey was conducted between April and November 2024 within the EAES Rising Stars Academy 2023-2024. In a Delphi-like process, 53 questions addressing surgeon characteristics, institutional practice, and the use of ICG and FE were developed and distributed worldwide. A total of 1367 respondents from 80 countries participated (mean age 64 ± 10 years). ICG was available at 76% of institutions, and 67% of surgeons reported using it. Timing varied: before transection 40%, after transection 7%, before anastomosis 17%, after anastomosis 25%, and both before and after 11%. A fixed dose was used by 71% and weight-based dosing by 29%. FE was performed by 51% of surgeons, with 23% reporting routine intraoperative use. Key barriers included gastroenterologist-led practice (28%), reliance on alternative techniques (20%), and lack of training (19%). Substantial variability was observed across all domains. This survey revealed significant heterogeneity in the use of ICG and FE in colorectal surgery. Although ICG is more widely implemented, both techniques lack standardized protocols. Moreover, FE adoption remains limited by training and access. Training should be enhanced and could represent a key area of focus for future EAES programs.
Colony-stimulating factor 1 receptor-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) is a rare, fatal, autosomal-dominant neurodegenerative disorder caused by pathogenic CSF1R variants and characterized by progressive cognitive, neuropsychiatric, and motor dysfunction, white matter lesions on brain imaging, and white matter demyelination, swollen axons, and pigmented glial cells on pathology. Limited data regarding clinical, biofluid or radiological biomarkers of disease severity are available, and no clinical trial endpoints have yet been validated. The objectives of this first-of-its-kind, prospective, observational natural history study were to characterize the clinical trajectory of CSF1R-ALSP and to identify and evaluate key biomarkers and clinical endpoints indicative of disease severity and progression. ILLUMINATE (NCT05020743) was a multicentre, noninterventional natural history study of adults with CSF1R-ALSP and prodromal carriers of CSF1R variants. Participants were followed for up to 36 months, with clinical assessments, fluid biomarkers and volumetric MRI assessments of brain atrophy collected at screening and every 6 months. This study was terminated early (4 June 2025). The analyses reported here include data collected through 19 February 2025. Of 53 participants, 19 were prodromal and 34 were symptomatic (11 of whom had a history of haematopoietic stem cell transplant and 23 who did not). Mean participant age was 47.8 (standard deviation, 4.5) years, and 36.4% were female. Prodromal participants remained relatively stable over 36 months, with little change in neurological function, neurodegeneration biomarkers or radiological disease burden. Impaired neurological function, MRI characteristics of CSF1R-ALSP, and elevated NfL (neurofilament light chain; neurodegeneration biomarker) and GFAP (glial fibrillary acidic protein; astrogliosis biomarker) levels were more pronounced at baseline and often showed progression over time among symptomatic participants who had not previously received haematopoietic stem cell transplant compared with participants who had previously received haematopoietic stem cell transplant. Significant correlations were observed at baseline and longitudinally between MRI measures of brain atrophy and clinical outcome measures. Based on the fluid biomarkers, MRI measures, and clinical outcome assessments evaluated here, active neurodegeneration, widespread changes visualized on brain MRI, and impaired cognitive and motor function were observed in symptomatic patients with CSF1R-ALSP. The neurological impairment can be assessed using the Montreal Cognitive Assessment and Cortical Basal ganglia Functional Scale. Our data suggest that quantification of brain atrophy using MRI volumetry is a potential biomarker of disease severity and progression in CSF1R-ALSP. It is hoped that this report will contribute to the understanding of disease progression in CSF1R-ALSP and inform future drug development.
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Epidemiological and phylogenetic evidence linking raw meat and raw dog food (RDF) feeding with dogs shedding antibiotic-resistant (ABR) Escherichia coli is strong. However, evidence for close phylogenetic relatedness between E. coli from meat/RDF and those causing opportunistic human infections is limited, partly due to non-contemporaneous sampling. Here, we characterised ABR E. coli from meat/RDF in Bristol, UK in 2022/23, and measured their phylogenetic relatedness to isolates causing human urinary tract and bloodstream infections in Bristol in 2023. We monitored ABR E. coli positivity in raw chicken, beef, pork and lamb from 15 large-chain stores and chicken-based RDF from 15 pet stores, selecting 200 E. coli for Illumina WGS. E. coli causing 1,182 human infections were sequenced, irrespective of resistance phenotype. Significant phylogenetic relatedness between meat and RDF E. coli was observed, consistent with common supply-chain origins. Phylogroup A/B1 and B2 E. coli dominated meat/RDF and human isolates, respectively. Resistance to antibiotics predominantly used in farmed animals dominated meat/RDF isolates; resistance to antibiotics extensively used in humans dominated human isolates. Four meat/RDF-infection E. coli pairs (three ST69 and one ST117) differed by <20 core-genome SNPs, representing 2% of meat/RDF and 0.2% of human infection-causing E. coli. Each ST69 meat/infection pair member carried identical antibiotic resistance genes. Using contemporaneous, geographically focussed sampling, close phylogenetic relatedness between meat/RDF and human infection isolates was identified but was rare. Whilst transmission and risk cannot be inferred, these findings support the integration of raw meat and RDF into One Health ABR surveillance structures.
Prefrontal theta burst stimulation (TBS) - induced brain activation may offer insights into the therapeutic mechanisms underlying TBS. This study aimed to compare baseline TBS-induced prefrontal hemodynamic responses in individuals with major depressive disorder (MDD) and healthy controls (HCs), and to evaluate whether changes in stimulation-evoked responses are correlated with improvements in depressive symptoms following four weeks of daily TBS. Both MDD (n = 44; 70% females) and HCs (n = 45; 60% females) underwent a concurrent TBS/functional near-infrared spectroscopy (fNIRS) paradigm. MDD participants further received 20 sessions of intermittent TBS (iTBS) of the left dorsolateral prefrontal cortex, followed by post-treatment TBS/fNIRS measurements. TBS-evoked hemodynamic responses were analyzed using repeated-measures ANOVA and t-tests. Additionally, correlation analyses were conducted to assess the relationship between depressive symptom changes and prefrontal hemodynamic response changes following treatment. Significant increases in deoxyhemoglobin concentrations were observed both during and after TBS. However, no significant differences in TBS-induced hemoglobin responses were found between MDD participants and HCs. Notably, changes in individual TBS-induced hemodynamic responses after treatment significantly correlated with symptom reductions (r = -0.488, p = 0.037). These findings suggest that TBS-induced hemodynamic responses may reflect underlying neural changes that are functionally relevant to symptom improvement, highlighting their potential as neuroimaging markers for treatment monitoring in depression.
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Cultural repertoires can influence access to resources and fitness across species, impacting individuals' environmental niches and social networks. Such behaviours may induce potentially reversible changes in gene expression via epigenetic mechanisms like DNA methylation, thus capturing cultural behaviour on a molecular level. Some Indo-Pacific bottlenose dolphin (Tursiops aduncus) in Shark Bay, Western Australia, use marine sponges as foraging tools and exhibit differences in diet, sociality and survival compared to dolphins that use the same habitat but lack the tool-using know-how ('non-spongers'). We investigated the relationship between this culturally transmitted behaviour and skin DNA methylation patterns at 29 812 cytosine-phosphate-guanine (CpG) sites of the HorvathMammalMethylChip40. Machine learning models, based on differences in DNA methylation at specific CpG sites, showed moderate ability to discriminate between spongers (n = 23) and non-spongers (n = 73; area under the curve = 0.68). Permutation tests indicated that our main machine learning model performed significantly better than random at differentiating spongers from non-spongers, suggesting that DNA methylation patterns contain information associated with sponging behaviour. Our study on the nexus between epigenetics and cultural evolution opens a promising avenue of research on the molecular underpinnings of cultural practises, important to the biology of humans and other animals. This article is part of the theme issue 'Ecological epigenetics at the intersection of behaviour and life history variation in non-model animals'.
Immune dysregulation, immunosuppressive therapy and active inflammatory bowel disease (IBD) increase susceptibility to respiratory syncytial virus (RSV) infection. We evaluated the risk of RSV infection in patients with active and nonactive IBD. Using the TriNetX Analytics Network from October 2024 through March 2025, we identified adult patients (aged ≥18 years) with IBD. Patients were classified as having active IBD if they had recent IBD complications, IBD-related surgery, or elevated inflammatory markers (within preceding 6 months); those without recent complications,surgeries, or elevated inflammatory markers were classified as having nonactive IBD within the same period. Outcomes were assessed within 180 days after the index date and included RSV infection, bacterial pneumonia, intensive care unit (ICU) admission, and mechanical ventilation. Among 141 763 patients (47 883 patients with active IBD, 93 880 patients with nonactive IBD), 2879 patients with active IBD and 3583 with nonactive IBD received the RSV vaccination. After matching, each cohort included 46 308 patients. Active IBD was associated with higher odds of RSV infection (adjusted odds ratio [aOR], 1.55; 95% CI, 1.18-2.04), bacterial pneumonia (aOR, 2.58; 95% CI, 2.08-3.19), ICU admissions (aOR, 2.07; 95% CI, 1.88-2.28), and mechanical ventilation (aOR, 2.41; 95% CI, 2.01-2.88). RSV risk remained higher among patients with active IBD both with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD (aOR, 1.26; 95% CI, 0.78-1.79). Patients with active IBD had higher risk of RSV infection. Increased RSV risk was observed both among patients with active IBD with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD. Further prospective studies are needed to validate these findings.
We aimed to capture UK medical students' preferences regarding skin color terminology in medical education and in relation to how they describe their own skin tone, to better understand how we can develop more inclusive, diverse medical language for both educational and clinical settings.
To offer clinicians recommendations concerning breast cancer follow-up and surveillance after primary treatment. ASCO convened an Expert Panel to develop recommendations based on a systematic review and a formal consensus process. One randomized controlled trial (RCT) was identified and formed the evidentiary basis for the surveillance mammography guideline recommendation. No RCTs were identified that evaluated different follow-up approaches by risk of relapse in patients treated for early-stage breast cancer. Given the dearth of evidence identified in the systematic review of the literature, formal modified Delphi consensus-based recommendations were generated. The guideline offers recommendations on the role of a risk-based approach to the frequency and intensity of follow-up among patients with breast cancer in the adjuvant setting. Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Either virtual or in-person visits can be offered. Certain patients at high risk of cancer recurrence warrant closer surveillance, such as those patients with locally advanced disease or residual disease following neoadjuvant chemotherapy. Recommendations on the use of blood-based biomarkers and supplemental imaging are provided. Guideline recommendations will be updated once additional evidence-based tools become available to better individualize surveillance.Additional information is available at www.ascopubs.org/topics/asco-guidelines/breast-cancer.
Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly), which produces acetyl-coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated. We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) gene editing to inactivate Acly in cardiomyocytes of Myh6-Cas9 mice. In vivo positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to Acly knockdown. We conducted a multi-omics analysis using RNA sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. We observed reduced ACL abundance and activity in human heart tissue samples from patients with nonischemic cardiomyopathy, which correlated with decreased abundance of Krebs cycle intermediates. Using CRISPR/Cas9 gene editing, we found that cardiac-specific loss of ACL reduces acetyl-CoA synthesis, leading to altered cardiac metabolism characterized by increased glucose uptake and oxidation, impaired energy flux, and elevated AMP to ATP ratios, which collectively promote left ventricular dysfunction. Transcriptomic and mass spectrometry-based metabolomics, as well as proteomic data, reveal compensatory cardiac lipid remodeling and reduced histone 3 acetylation. This metabolic stress promotes activation of AMPK (AMP kinase) and PKA (protein kinase A), which in turn mediates YAP (Yes-associated protein) inhibition through phosphorylation. Stable isotope tracer studies combined with CardioNet simulations demonstrated that increased IDH1 (isocitrate dehydrogenase 1) activity prevents allosteric inhibition of glycolysis from cytosolic citrate accumulation. AAV9-mediated cardiac Idh1 deletion improved cardiac function and energy provision, reducing YAP phosphorylation and restoring downstream YAP signaling. Our findings suggest that ACL plays a pivotal role in cardiac metabolism through regulating lipid synthesis and cardiac function. Exploiting compensatory pathways of citrate metabolism may improve cardiac function during heart failure.
Genomic data from contemporary and historical samples often need to be coupled for evolutionary reconstructions of multitaxon complexes. However, the genetic data recovered from historical samples may result only in ultra-low coverage whole-genome sequences (ulcWGS; <0.15× depth), leading to inaccurate evolutionary inferences given a preponderance of missing data. Using the Galapagos giant tortoise radiation as a study system (Chelonoidis spp., composed of 13 extant and four extinct lineages), we assembled a novel methodological pipeline that removes potential noise introduced by the missing data and enhances the evolutionary signal from ulcWGS samples. We leveraged existing tools for phylogenomic placement (EPA-ng), population genomic structure (smartsnp) and admixture (Admixfrog, NGSadmix) to demonstrate that the evolutionary history of samples can be uncovered with sequencing depths as low as 0.008-0.139×. Importantly, these approaches do not use genotype imputation of the ulcWGS samples, which would require extensive reference datasets. Our application to two cases of extinct lineages of Galapagos giant tortoises, with and without references from the same lineage, demonstrates the general value of the approach. We confirm where the extinct lineages from San Cristóbal and Santa Fe islands fit into the Galapagos giant tortoise radiation, and that these lineages were evolutionarily distinct entities.
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Understanding the occurrence of arthropods in the Arctic relies heavily on distributional and taxonomic evidence, yet substantial gaps and inconsistencies in available data complicate interpretation. These limitations impact our understanding of ecologically-and medically-important groups such as the mosquitoes (Diptera: Culicidae), whose Arctic diversity and biogeography remain poorly resolved. Many species were originally described from limited material, often using morphological traits that differ from those observed in more thoroughly studied southern populations. Sparse and uneven sampling across the Arctic limits our ability to accurately assess species distributions, and missing or incomplete metadata further diminishes the scientific value of existing specimens. Collectively, these issues obscure patterns of biodiversity, hinder detection of climate‑driven range shifts, and constrain efforts to evaluate the vector potential of species capable of transmitting arboviruses. As concerns grow regarding the northward expansion of mosquito‑borne pathogens, the absence of reliable baseline data poses a major challenge for assessing current and future risks to human and animal health in Arctic ecosystems. This review synthesizes historical records of Canadian Arctic mosquitoes from early natural history expeditions beginning around 1820 to the present. We evaluate the taxonomic reliability, geographic accuracy, and research relevance of these records to determine which can serve as credible baselines for contemporary biodiversity assessments. By clarifying the strengths and limitations of the historical dataset, this review aims to support improved species distribution modeling, inform future surveillance efforts, and guide research priorities in a rapidly changing Arctic.
Lung metastases in patients with metastatic rhabdomyosarcoma (RMS) have not been treated uniformly across Europe. This provides comparison of the impact of whole lung irradiation (WLI). Lung-metastatic patients included in the Cooperative Weichteilsarkom Studiengruppe-IV 2002, European Pediatric Soft Tissue Sarcoma Study Group MTS 2008 or the Soft Tissue Sarcoma Registry received four- or six-drug chemotherapy, surgery, and/or irradiation (radiotherapy) of the primary tumor. Treatment of lung lesions consisted of metastasectomy, WLI, or no local treatment according to protocols. A total of 238 patients with lung-metastatic RMS were included. Half of these patients (n = 119/238) had lung metastases only (median age, 6.6 years), mainly classified as embryonal RMS (n = 93/119, 78%). Lung-only patients underwent metastasectomy (n = 17) and/or WLI (n = 31) or no local treatment of lung metastases (n = 71). Early complete response of lung metastases was associated with favorable 3-year overall survival (p = .009). A trend toward improved event-free survival after WLI could be identified in patients ≥10 years old (hazard ratio [HR], 2.7; 95% CI, 0.8-9.6), but not in patients under 10 years old (HR, 0.86; 95% CI, 0.44-1.66). Lung-relapse-free survival (lung-RFS) was not influenced by WLI or metastasectomy in the univariable and multivariable analyses. When analyzing all lung-metastatic patients (including those with metastases in other sites, n = 238), WLI in patients older than 10 years was a significant prognostic factor (HR, 2.2; 95% CI, 1.0-4.9). The analysis failed to show a significant benefit of WLI in patients with lung-metastatic RMS, apart from the subgroup of patients older than 10 years. Lung-RFS was not influenced by WLI.
Cushing's Disease (CD) is caused by pituitary adenomas, leading to hypercortisolism. This condition burdens patients socioeconomically, with a reduced quality of life and higher mortality. Transsphenoidal surgery (TSS) is the first-line treatment, offering a 78% remission rate. This study aims to identify factors influencing TSS outcomes to find the predictors of remission for improved treatment planning. A systematic search of electronic databases was performed based on the PRISMA guideline. Studies were selected if they reported data on remission and non-remission groups. A comparative meta-analysis was performed based on the variable type. This review included 11,666 patients treated with TSS for CD, with a remission rate of 73.88%. The mean age was 39.1 years, predominantly female (75.21%), with an average follow-up of 53.29 months. Remission rates were higher in patients with positive MRI results (78.47% vs. 66.11%, P < 0.01), microadenomas (79.16% vs. 64.70%, P < 0.01), without cavernous sinus invasion (78.50% vs. 47.54%, P < 0.01), first-time TSS (81.98% vs. 63.80%, P < 0.01), selective adenectomy surgery (81.24% vs. 64.54%, P < 0.01), and positive adenoma pathology (80.37% vs.54.65%, P < 0.01). Patients who achieved long-term remission exhibited significantly lower immediate post-operative serum cortisol, Adrenocorticotrophic Hormone (ACTH), and urinary-free cortisol (UFC) levels. The risk of bias was low across most studies. Our systematic review and meta-analysis demonstrate MRI findings, histopathology, tumor size, post-operative cortisol, ACTH, UFC, tumor invasion, and repetition of surgery as predictors of remission. These factors should be considered in patient selection for TSS to maximize clinical benefits.
Lower limb cellulitis accounts for 1.5%-2% of visits to Australasian emergency departments. Antibiotics are considered the cornerstone of management, but despite prioritisation by consumers, acute interventions to manage pain and inflammation and cellulitis recurrence prevention strategies remain understudied beyond small pilot trials. We aimed to assess clinicians' current practices, areas of clinical uncertainty and willingness to randomise patients to interventions, including demarcation lines, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, compression therapy, exercise, antibiotic prophylaxis and a hypothetical streptococcal vaccine for cellulitis prevention. A cross-sectional online survey, consisting of 22 questions assessing clinical practices and equipoise for randomisation into a future trial, was distributed to practicing Australasian clinicians specialising in infectious diseases, lymphoedema physiotherapy, internal medicine, emergency medicine or surgery. A total of 250 (response rate of ~10%) respondents completed the survey from 77 unique institutions. Lower limb cellulitis was common, with 91 respondents reporting >200 presentations at their institution annually. For most assessment, management and prevention strategies, there was wide variation in clinical practice. Overall, respondents were comfortable considering randomising to possible interventions including drawing (or removing) a line around cellulitis (91.3%), NSAIDs (90.2%) or corticosteroids (74.2%), acute compression (90.7%), exercise (96.4%) and prevention strategies such as injectable benzathine penicillin G (BPG; 87.2%) or a hypothetical streptococcal vaccine (92.7%). Most (62%) respondents expressed interest in a clinical trial of lower limb cellulitis. Novel interventions for acute management and secondary prevention of cellulitis have clinical equipoise. A large, multicentre cellulitis trial is likely to be feasible in Australasian hospitals.
Follow-up of pre-licensure trial participants potentially informs a vaccine's long-term safety profile. This prospective study enrolled participants from the first clinical trials of ChAdOx1 nCoV-19 vaccine, many of whom subsequently received COVID-19 vaccines in the UK vaccination programme. Serious adverse events (SAEs) and adverse events of special interest (AESIs) were captured. AESI selection was based on Brighton Collaboration definitions. Between September 2021 and April 2022, 4470 participants enrolled (58% female, median age 50 years); 3845/4470 (86.0%) completed the study. Median follow-up was 11.77 months; total follow-up was 48,116 person-months. There were 174 SAEs and 71 AESIs (33 events recorded as both) in 195 participants, including 5 deaths. Immunology data were available for a small subset of participants; total IgG against trimeric SARS-CoV-2 spike protein tended to increase during the study. Although no emergent safety signals were detected, continued post-marketing surveillance remains imperative, particularly for neurological disorders. 2021-003382-36.