Tag: pubmed

Biophys J. 2026 May 15:S0006-3495(26)00360-7. doi: 10.1016/j.bpj.2026.05.020. Online ahead of print.

ABSTRACT

Understanding how chromatin folds in three dimensions remains challenging because most experimental assays capture low-dimensional projections of an underlying, highly heterogeneous polymer. Here we present an ensemble-based interpretive framework built on the previously introduced Self-Returning Excluded Volume (SR-EV) model, a minimal generator of chromatin conformations using a nucleosome-indexed coarse-grained representation based on stochastic return rules and excluded-volume geometry. Despite its simplicity, SR-EV recapitulates key experimental signatures across scales: heterogeneous nanoscale packing domains resembling ChromEMT and ChromSTEM observations, sparse and highly variable single-configuration contact patterns analogous to single-cell chromosome conformation capture (Hi-C), and robust ensemble-level contact enrichment consistent with topologically associating domains (TADs). In this framework, Hi-C loop and TAD signatures are interpreted as ensemble-level statistical enrichments rather than invariant features of single-cell conformations. SR-EV is explicitly designed to generate large ensembles of complete three-dimensional chromatin configurations that can be projected consistently onto two-dimensional contact maps and one-dimensional genomic profiles. By introducing architectural-protein effects only through ensemble selection rather than explicit forces, SR-EV supports a separation between intrinsic polymer geometry and regulatory bias and suggests that TAD-like features can emerge as statistical enrichments rather than deterministic three-dimensional structures. Coordination number and probe-based accessibility computed directly from SR-EV provide a unified link between three-dimensional packing, two-dimensional contact maps, and one-dimensional genomic profiles. The main contribution of this work is to show, within a single coarse-grained framework, how these multimodal observables arise as linked projections of the same heterogeneous chromatin ensemble through averaging and conditional sampling. Together, these results establish SR-EV as a minimal and geometrically grounded mesoscale reference framework for interpreting how heterogeneous chromatin ensembles give rise to multimodal experimental observables, while remaining consistent with the fact that chromatin organization is realized in individual cells.

PMID:42143406 | DOI:10.1016/j.bpj.2026.05.020

Biophys J. 2026 May 15:S0006-3495(26)00362-0. doi: 10.1016/j.bpj.2026.05.022. Online ahead of print.

ABSTRACT

Biological membranes are compositionally asymmetric, with distinct lipid mixtures in each leaflet, yet how this asymmetry influences lateral membrane organization remains poorly understood. Here, we use calcium-induced hemifusion to generate asymmetric giant unilamellar vesicles (aGUVs) and investigate how lipid composition modulates interleaflet coupling of liquid-liquid phase separation. Symmetric GUVs composed of cholesterol, the high-melting lipid DPPC, and a low-melting phosphatidylcholine (either 14:1-PC or 16:1-PC) were prepared at compositions exhibiting coexisting liquid-ordered (Lo) and liquid-disordered (Ld) phases. Hemifusion with a uniformly mixed supported lipid bilayer selectively altered the outer leaflet composition, producing aGUVs with controlled but variable asymmetry. Fluorescence measurements of outer leaflet exchange revealed substantial vesicle-to-vesicle variability, resulting in overlapping populations of phase-separated and uniformly mixed aGUVs. To account for this variability, we developed a statistical framework that jointly models the distribution of exchange fractions and the location of a phase boundary in asymmetric composition space, allowing all observed vesicles to contribute to the analysis. We find that aGUVs containing 14:1-PC require significantly greater outer leaflet exchange to abolish phase separation than those containing 16:1-PC. Only in the 14:1-PC system do we observe vesicles exhibiting coexistence of distinct anti-registered phases, a theoretically predicted but rarely observed regime consistent with large hydrophobic mismatch. By expressing symmetric and asymmetric miscibility boundaries in a common compositional framework, we introduce a phenomenological parameter, Δ^∗, that quantifies the direction and strength of interleaflet coupling. These results demonstrate that modest changes in lipid chain length can markedly alter asymmetric phase boundaries, and provide a quantitative link between experimental observations, leaflet dominance concepts, and coupled-leaflet theories of membrane organization.

PMID:42143405 | DOI:10.1016/j.bpj.2026.05.022

Intern Emerg Med. 2026 May 16. doi: 10.1007/s11739-026-04385-z. Online ahead of print.

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is strongly linked to tobacco smoking, and smoking cessation is central to disease management. E-cigarettes are widely promoted as a harm reduction option in the United Kingdom, yet patterns of use among people with COPD remain poorly described. This study examined the prevalence and correlates of current e-cigarette use among individuals with COPD in Scotland using data from the 2018 to 2022 Scottish Health Survey. The analysis included adults aged 16 years and above who reported a COPD diagnosis (n = 891). Survey-weighted logistic regression was used to estimate crude and adjusted associations between sociodemographic, behavioural, and health characteristics and current e-cigarette use, with additional models stratified by smoking status and smoking intensity. The weighted prevalence of current e-cigarette use was 11.9% (95%CI 9.7-14.5). Older age was associated with lower odds of current use (adjusted odds ratio [aOR] 0.60; 95%CI 0.41-0.89), while socioeconomic deprivation showed a positive gradient (aOR 1.21; 95%CI 1.01-1.45). Smoking status was the strongest correlate: odds were higher among ex-smokers (aOR 10.80; 95%CI 1.66-70.06) and current smokers (aOR 14.86; 95%CI 2.37-93.33) compared with never-smokers. Among current smokers, younger age, female sex, and higher deprivation were associated with use, whereas no clear determinants were identified among former smokers. Light and moderate smokers had greater odds of current e-cigarette use than non-smokers, while heavy smokers did not differ. Overall, e-cigarette use was relatively common and concentrated among younger, more deprived adults with a smoking history. Longitudinal studies are needed to determine the implications for respiratory outcomes.

PMID:42142305 | DOI:10.1007/s11739-026-04385-z

Arch Orthop Trauma Surg. 2026 May 16;146(1):188. doi: 10.1007/s00402-026-06330-3.

ABSTRACT

PURPOSE: Hidden blood loss (HBL) is an underrecognized contributor to total perioperative blood loss after hip fracture surgery. This study aimed to quantify HBL during the first three postoperative days following proximal femur fracture fixation and to assess the impact of preoperative anticoagulant therapy on blood loss and transfusion requirements.

METHODS: A retrospective cohort study was conducted including patients aged ≥ 65 years who underwent surgical fixation of proximal femur fractures at a level I trauma center between January 2020 and December 2022. Total blood loss was estimated from perioperative hemoglobin changes and calculated blood volume. Patients were stratified according to anticoagulant use, and logistic regression analysis was performed to identify independent predictors of increased blood loss.

RESULTS: Among 260 patients analyzed, median total blood loss was 1184 ml, and 25% experienced losses exceeding 1675 ml. High blood loss correlated significantly with anticoagulant use, higher BMI, and longer operative time (p < 0.001). In multivariate analysis, anticoagulant therapy (particularly direct oral anticoagulants) remained an independent predictor of high blood loss (OR 3.06; 95% CI 1.47-6.37; p = 0.003). Patients in the highest quartile required significantly more transfusions, though short-term mortality did not differ.

CONCLUSION: Hidden blood loss after proximal femur fracture surgery is frequent and clinically relevant. Anticoagulant use, elevated BMI, and prolonged operative duration independently increase bleeding risk. Awareness of these predictors may support optimized perioperative management and transfusion planning in elderly fracture patients.

PMID:42142301 | DOI:10.1007/s00402-026-06330-3

Clin Drug Investig. 2026 May 16. doi: 10.1007/s40261-026-01561-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The interventional landscape for psoriasis has expanded considerably with the introduction of systemic and biologic agents, intensifying the importance of comprehensive adverse event (AE) documentation to inform safe clinical practice. While regulatory initiatives such as the Food and Drug Administration Amendments Act Final Rule (FDAAA Final Rule) were designed to enhance clinical trial transparency, disparities between AE data presented in ClinicalTrials.gov and peer-reviewed literature continue to occur, potentially complicating interpretation of publicly available harms information used in evidence synthesis and clinical decision-making. Variability in how serious adverse events (SAEs), other adverse events (OAEs), deaths, and treatment discontinuations due to AE are documented can distort safety perceptions and influence clinical practice. This study compares AE reporting between ClinicalTrials.gov and corresponding peer-reviewed publications for psoriasis clinical trials and evaluates whether completeness and concordance differ before versus after implementation of the FDAAA Final Rule.

METHODS: We performed a cross-sectional analysis using systematic retrieval of psoriasis trials from ClinicalTrials.gov with results posted between 2009 and 2024. Data on AEs-encompassing SAEs, OAEs, treatment discontinuation due to AE, and deaths-were independently abstracted by two reviewers, with disagreements resolved through adjudication. Trials were categorized according to FDA regulatory status, and variations in AE documentation were examined using descriptive statistics, chi-squared tests, Bland-Altman and funnel plots, and regression modeling.

RESULTS: The study’s primary endpoint was completeness and agreement of AE documentation between ClinicalTrials.gov and corresponding peer-reviewed publications across four predefined domains: SAEs, OAEs, discontinuation due to AE, and death. Pre-Final Rule AE reporting patterns were mixed across domains. After implementation of the FDAAA Final Rule, registry entries more consistently reported SAEs, OAEs, and mortality than corresponding publications. Although death documentation in registry entries showed improvement after the rule’s enactment, publications demonstrated persistent inconsistency. Following implementation of the FDAAA Final Rule, SAEs were present in 53% of registry records versus 40% of publications. OAEs were captured in 51% of registry entries but only 22% of publications. Disparities in SAE totals occurred in over 90% of trials, frequently with registry entries recording higher counts. Numerous discrepancies stemmed from incomplete calculations, ambiguous characterizations, or AE information confined to narrative text. Both visual and statistical assessments revealed a pattern of underreporting in publications, with minimal temporal improvement irrespective of trial scale or sponsorship type.

CONCLUSIONS: Notwithstanding current regulatory frameworks, AE documentation for psoriasis trials remains fragmented with substantial inconsistency between registry and published data. These shortcomings undermine rigorous safety assessment and evidence-based clinical recommendations. Improved patient care requires increased integration of registry data into evidence synthesis, better clarification of AE definitions, and standardized AE reporting practices.

REGISTRATION: Preregistered on The International Prospective Register of Systematic Reviews (PROSPERO; CRD420251081207) and Open Science Framework (4jaz3).

PMID:42142276 | DOI:10.1007/s40261-026-01561-z

Eur J Nucl Med Mol Imaging. 2026 May 16. doi: 10.1007/s00259-026-07918-y. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the feasibility of non-invasively identifying bone marrow involvement (BMI) in follicular lymphoma (FL) using baseline ¹⁸F-FDG PET/CT combined with multidimensional feature fusion, and to compare the impact of different bone marrow volume-of-interest (VOI) frameworks on model performance.

METHODS: This retrospective study included 187 patients with newly diagnosed FL, 93 of whom had BMI. Based on baseline ¹⁸F-FDG PET/CT, two bone marrow VOI frameworks were constructed: a pelvic VOI framework and a spine-pelvis VOI framework. Clinical features, conventional imaging features, radiomic features, and deep learning features were extracted. A hierarchical feature screening strategy was employed: clinical and conventional imaging features were screened using univariate logistic regression, Spearman’s correlation analysis, and multivariate logistic regression, whereas high-dimensional radiomic and deep learning features were screened using LASSO regression combined with the Boruta algorithm. Based on the selected features, six different modelling schemes were developed. The optimal scheme was selected using the area under the receiver operating characteristic curve (AUC) in the independent validation set as the primary metric. Under the optimal scheme, the performance of seven machine learning models-logistic regression (LR), support vector machine (SVM), gradient boosting machine (GBM), neural network (NN), random forest (RF), k-nearest neighbours (KNN), and adaptive boosting (AdaBoost)-was further compared. SHAP analysis was used to interpret the key features of the final model and the direction of their contributions.

RESULTS: Compared with the non-BMI group, the BMI group was more likely to present with widespread regional lymph node involvement, B symptoms, larger lymph node lesions, as well as lower Hb, higher LDH, lower Apo A, lower eGFR, and higher β2-MG levels (all P < 0.05). Under both VOI frameworks, the BMI group exhibited higher bone marrow FDG uptake intensity and metabolic burden, as reflected by higher values of conventional PET/CT features, including SUVmean, Standard Deviation (PET), RMS, 25th Percentile Value, Median, 75th Percentile Value, TLG, Glycolysis Q2-Q4, SAM, and SUVpeak (all P < 0.05). Multivariate logistic regression analysis indicated that regional lymph node involvement and β2-MG consistently remained independent predictors across both VOI frameworks, whereas SUVmean retained statistical significance only within the pelvic VOI framework. A comparison of six modelling schemes revealed that the scheme integrating the spine-pelvis VOI framework with clinical features, conventional imaging features, and radiomic features performed best. Under this scheme, the GBM model achieved the best overall performance on the independent validation set (AUC = 0.906, Accuracy = 0.877, Precision = 0.926, Sensitivity = 0.833, Specificity = 0.926, F1 score = 0.877). SHAP analysis revealed that, in addition to LNr (≥ 5) and β2-MG, first-order statistical features such as PET-Orig-FO-IQR, as well as texture features derived from wavelet/LBP transformations-including PET-Wav-HLL-NGTDM-Strength, PET-Wav-HLL-GLRLM-SRHGLE, CT-LBP3D-m1-GLCM-MCC, and PET-LBP3D-m2-GLSZM-SAHGLE-also made significant contributions. These findings suggest that BMI-associated imaging phenotypes are characterised not only by increased bone marrow metabolism but also by remodelling of the grey-level distribution and spatial heterogeneity within the bone marrow.

CONCLUSION: Bone marrow involvement in follicular lymphoma is associated with higher tumour burden and altered metabolic heterogeneity within the bone marrow. A PET/CT-based radiomic-clinical model showed good performance for non-invasive BMI prediction, and the spine-pelvis VOI framework outperformed the pelvic VOI framework alone. The final GBM model may provide a feasible imaging biomarker for complementary baseline assessment of BMI in FL.

PMID:42142271 | DOI:10.1007/s00259-026-07918-y

Metabolomics. 2026 May 16;22(3):74. doi: 10.1007/s11306-026-02457-x.

ABSTRACT

INTRODUCTION: We present a simple test to assess whether a metabolomics dataset is fit-for-purpose. Current qualitycontrol approaches do not directly evaluate the ability to recover biologically meaningful perturbations.

OBJECTIVES: To evaluate whether known drug-induced metabolic perturbations can serve as internal benchmarks fordataset quality.

METHODS: In a study (the TROMBOLOME study, unrelated to allopurinol therapy), 1,000 serum samples were analyzedwith one targeted and two untargeted metabo lomics panels. Samples were classified as allopurinol-positive (N=19)using detection of allopurinol analytical targets. Endogenous metabolite markers of allopurinol therapy wereevaluated based on hypotheses derived from the literature. Statistical evaluation was performed using Mann-Whitney U-tests.

RESULTS: The hypothesis of upregulation was supported for xanthine, orotate, and orotidine (p < 0.0001) inallopurinol-positive cases (N = 19). These findings demonstrate repro ducibility of well-characterized metabolicperturbations within the dataset.

CONCLUSION: In the absence of external quality assessment schemes for untargeted metabolomics, such benchmarkscould provide a practical way to evaluate whether datasets are suitable for downstream biological interpretation.The proposed targeted exposomics approach complements traditional QC metrics by assessing biologicalrecoverability.

PMID:42142266 | DOI:10.1007/s11306-026-02457-x

Support Care Cancer. 2026 May 16;34(6):546. doi: 10.1007/s00520-026-10786-9.

ABSTRACT

BACKGROUND: The Multinational Association for Supportive Care in Cancer (MASCC) Risk Index is the most widely used tool for stratifying febrile neutropenic cancer patients as low or high risk for serious complications. Studies evaluating its discriminative performance have relied predominantly on sensitivity, specificity, receiver operating characteristic (ROC) curves, and c-statistics-metrics that are mathematically elegant but have limited direct utility in clinical decision-making at the bedside.

METHODS: Sensitivity and specificity data from Rivest et al. [13], the original Klastersky et al. derivation study [3], and the Zheng et al. meta-analysis [10] were used to calculate positive and negative likelihood ratios. Posttest probabilities were derived using Bayesian updating (pretest odds × LR = posttest odds), with a cohort pretest probability of complications of 35%. Likelihood ratios for procalcitonin (Ahn et al.) were applied sequentially to demonstrate the compounding of independent predictors.

RESULTS: Applying Rivest et al. data in the inverted framing (i.e., predicting complication presence), a MASCC score > 21 yields a posttest probability of neutropenic complications of approximately 22%, and MASCC < 21 yields 65%. When procalcitonin ≥ 0.5 ng/mL is added to a high-risk MASCC score, the posttest probability rises to 85%; when procalcitonin is negative in a low-risk patient, it falls to 11%. Likelihood ratios varied meaningfully across Klastersky, Rivest, and Zheng (LR + range: 1.98-4.00; LR – range: 0.29-0.51), reflecting heterogeneity in populations, outcome definitions, and study settings.

CONCLUSIONS: Unlike sensitivity/specificity and predictive values, LRs are relatively independent of outcome prevalence, making them more transportable across clinical settings, though they are not immune to population and spectrum effects, stopping at sensitivity, specificity, ROC curves, and mathematical completeness but clinical incompleteness. Clinicians, who are the end-users of these tools, deserve the metric that speaks their language: the updated probability that this patient, in front of them, will experience harm.

PMID:42142265 | DOI:10.1007/s00520-026-10786-9

Metabolomics. 2026 May 16;22(3):76. doi: 10.1007/s11306-026-02455-z.

ABSTRACT

BACKGROUND: At the end of lactation (mammary involution), dynamic changes in milk components occur in all mammals. The time to reach complete cessation varies among taxa and species. The involution of cows, sheep, and goats (Bovidae) has been reported, but limited information is available on giraffes.

OBJECTIVES: Characterise organic acids and amino acids in the milk of giraffes at involution.

METHODS: Milk was obtained from five giraffes. A LC-MS/MS metabolomics approach was followed, and statistical analysis of the data was done using MetaboAnalyst 6.0.

RESULTS: There were 38 organic acids and 45 amino acids measured in the giraffe milk. The organic acids indicate a decrease in Krebs cycle intermediates. Lower citrate levels are associated with lower lactose levels, indicating reduced osmotic regulation. Lower uracil and orotic acid indicate decreased pyrimidine synthesis and eventual nucleotide synthesis. Increased amino acid content is not devoted to protein synthesis, but to other functions, specifically as antioxidants, redox buffering, and cytoprotection. Increased histidine, serine and methionine promote protein degradation and one-carbon metabolism. Lysine catabolites lead to decreased levels of energy metabolites and to stress adaptation. Aromatic amino acids modulate the supply of immune and neuroactive metabolites.

CONCLUSIONS: During involution, the regulation of organic acids suggests reduced Krebs cycle activity, indicating a transition from high biosynthetic to catabolic activity. Likewise, amino acids have other functions, specifically antioxidant, redox-buffering, and cytoprotection.

PMID:42142263 | DOI:10.1007/s11306-026-02455-z

Support Care Cancer. 2026 May 16;34(6):545. doi: 10.1007/s00520-026-10753-4.

ABSTRACT

PURPOSE: While physical activity, sedentary behavior, and sleep have individually been linked to long-term outcomes in cancer survivors, few studies have evaluated their synergistic effects across a full 24-h period. This study aimed to examine the association between adherence to the Canadian 24-Hour Movement Guidelines and mortality risk in a nationally representative sample of US cancer survivors.

METHODS: Data from 2551 cancer survivors participating in the 2007-2018 National Health and Nutrition Examination Survey were analyzed. Adherence to the 24-Hour Movement Guidelines for aerobic physical activity, sedentary behavior, and sleep was summed to categorize participants into four groups. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cancer-specific mortality.

RESULTS: The proportions of participants meeting no, one, two, and three guidelines were 14.4%, 38.6%, 34.4%, and 12.6%, respectively. Over a median follow-up of 70 months, 617 deaths occurred, of which 261 were attributed to cancer. Compared to those meeting no guideline, HRs (95% CIs) for those meeting one, two, and all three guidelines were 0.72 (0.55-0.95), 0.59 (0.43-0.81), and 0.55 (0.38-0.81), respectively, for all-cause mortality, and 0.47 (0.29-0.76), 0.53 (0.33-0.85), and 0.22 (0.10-0.49), respectively, for cancer-specific mortality. Subgroup analysis showed that the association between cumulative adherence to the guidelines and all-cause mortality was stronger among individuals with a body mass index ≥ 30 kg/m².

CONCLUSIONS: Greater integrated adherence to the 24-h movement guidelines was associated with a progressive reduction in mortality risk among US cancer survivors, especially those with obesity.

PMID:42142261 | DOI:10.1007/s00520-026-10753-4