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At least 19 recordsLinked to original sources

Automated segmentation and length measurement of metacarpal and phalangeal bones for hand radiograph evaluation.

Evaluating hand and wrist radiographs is essential in pediatric endocrinology and clinical genetics, particularly for the assessment of suspected skeletal anomalies. In this study, we present Auto-Bone-Caliper, an automated system for the segmentation and length measurement of metacarpal and phalangeal (M&P) bones, trained and evaluated on public datasets comprising both normal and dysmorphic cases. We first introduce InstanceSAM, a two-stage framework that detects and segments all 19 M&P bones in pediatric hand radiographs, achieving Dice scores of 98.7% for normal bones and 95.0% for dysmorphic bones. We further develop and evaluate three methods for bone-length estimation, identifying a k-means-based approach as the most accurate, with relative errors of 2.2% for normal bones and 4.5% for dysmorphic bones. Our automated pipeline, Auto-Bone-Caliper, integrates InstanceSAM with the k-means-based length-estimation method. To enable scale-independent downstream analyses, we derive relative bone-length measures from the automated measurements. Using these relative measures, we statistically compare measurements obtained using Auto-Bone-Caliper on an independent dataset with a healthy reference catalog of normal bone morphologies, observing a high level of agreement (Wasserstein-1 distance = 0.012). Finally, we demonstrate a potential clinical use case of Auto-Bone-Caliper by obtaining relative metacarpophalangeal pattern profiles for three genetic conditions, namely Turner syndrome, achondroplasia, and pseudohypoparathyroidism. Our results highlight the potential of the Auto-Bone-Caliper to streamline and standardize M&P length measurement, providing an objective and reproducible tool suitable for clinical application.

Humans

Improvement the accuracy and reproducibility of telomere length measurement utilizing qPCR.

Telomere length serves as a well-established molecular biomarker for evaluating aging and age-associated diseases. Among various methods, quantitative PCR for telomere length detection is convenient, rapid, cost-effective, and capable of high-throughput analysis in large epidemiological cohorts. However, numerous studies have indicated that issues related to differences in DNA quality caused by DNA extraction process significantly affect the accuracy and reproducibility of qPCR-based telomere length quantification. Initially, we established a model of DNA integrity variation, by utilizing nucleic acid endonucleases of serial activity units to cleave genomic DNA, generating DNA with varying degrees of degradation. The integrity of DNA templates decreases, the reduction of long fragments and the increase of short fragments in the mixed telomere products are the causes of the disruption in Ct values. Moreover, compared with longer reference gene amplicons, the short-segment internal gene reference can reduce the impact of genomic integrity on its amplification. Subsequently, we utilized additional gel excision purification to reduce degradation products. It was found that gel excision processing provides the best stability for telomere length detection with the lowest coefficient of variation. Additionally, the introduce of another calibrator sample, which is used for to adjust the T/S value of the test sample, narrows the deviation between qPCR-derived telomere length and gold-standard Terminal Restriction Fragment (TRF) measurements. Collectively, these results reveal that gel excision purification supports stable telomere detection. Calculating the correction coefficient incorporating the short internal reference and calibrator minimizes measurement deviations relative to sample TRF values.

Telomere

ERCnet: Phylogenomic Prediction of Interaction Networks in the Presence of Gene Duplication.

Assigning gene function from genome sequences is a rate-limiting step in molecular biology research. A protein's position within an interaction network can potentially provide insights into its molecular mechanisms. Phylogenetic analysis of evolutionary rate covariation (ERC) in protein sequence has been shown to be effective for large-scale prediction of functional relationships and interactions. However, gene duplication, gene loss, and other sources of phylogenetic incongruence are barriers for analyzing ERC on a genome-wide basis. Here, we developed ERCnet, a bioinformatic program designed to overcome these challenges, facilitating efficient all-versus-all ERC analyses for large protein sequence datasets. We simulated proteome datasets and found that ERCnet achieves combined false positive and negative error rates well below 10% and that our novel "branch-by-branch" length measurements outperforms "root-to-tip" approaches in most cases, offering a valuable new strategy for performing ERC. We also compiled a sample set of 35 angiosperm genomes to test the performance of ERCnet on empirical data, including its sensitivity to user-defined analysis parameters such as input dataset size and branch-length measurement strategy. We investigated the overlap between ERCnet runs with different species samples to understand how species number and composition affect predicted interactions and to identify the protein sets that consistently exhibit ERC across angiosperms. Our systematic exploration of the performance of ERCnet provides a roadmap for design of future ERC analyses to predict functional interactions in a wide array of genomic datasets. ERCnet code is freely available at https://github.com/EvanForsythe/ERCnet.

Gene Duplication

Genomic and computational analysis of variants in telomere regulatory genes in subjects with bone marrow failure.

Telomere Biology Disorders (TBDs) are a genetically heterogeneous and often under-recognized cause of Bone Marrow Failure Syndromes (BMFS), driven by defective telomere maintenance and progressive telomere attrition. We performed an integrated genomic, telomeric and computational analysis in 118 subjects presenting clinical features of BMFS to delineate the contribution of Telomere Regulatory Genes (TRGs) variants to disease pathogenesis. Whole exome sequencing (WES) identified pathogenic (18.18%), likely pathogenic (27.27%) and rare variants of uncertain significance (54.54%) in 27 subjects (22.9%) across five TRGs: RTEL1, TERT, TINF2, NOP10, and WRAP53. Telomere Length (TL) assessment revealed significant telomere shortening in TRG variant-positive subjects compared with age-matched controls, with the most profound attrition observed in individuals harboring de novo TINF2 gene variants. RTEL1 emerged as the most frequently affected gene, with recurrent clustering of variants within its C-terminal regulatory region. A familial NOP10 variant, Asp12His, segregated with cutaneous pigmentation and hematological abnormalities consistent with the established role of NOP10 in dyskeratosis congenita, further broadening the known mutational spectrum of the gene. Structure-guided in-silico analyses predicted that both novel and recurrent variants disrupt protein stability, telomerase assembly or trafficking and shelterin complex integrity. Reduced TERT expression and a significant inverse correlation between telomere length and clinical severity further underscored the functional impact of TRG defects. Collectively, this study provides the first comprehensive characterization of TRG variants in the Indian BMFS cohort and highlights the utility of integrating genomic sequencing, telomere length measurement and computational modeling to improve diagnostic precision, variant interpretation and clinical stratification in TBDs.

Journal Article

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the &#x3b2; - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher &#x3b2; values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans

Fins as a reliable surrogate tissue for age-related changes of telomeres and DNA methylation in gonads of a short-lived fish.

Senescence is a multifactorial and individualised process of age-related physiological decline. Cellular markers, such as telomere length and DNA methylation, can reveal subtle changes associated with chronological age or expected lifespan. In this study, we evaluated the utility of fin tissue as a surrogate for assessing telomere length and proportion of DNA methylation in the gonads of a small, short-lived laboratory fish, the turquoise killifish (Nothobranchius furzeri). We collected fin and gonadal tissues from both females and males at three different ages. We extracted DNA to measure telomere length via terminal restriction fragment (TRF) analysis and global DNA methylation levels using double-digest restriction-associated DNA sequencing (ddRADseq). Our results show a notable correspondence between telomere length and DNA methylation patterns in fin and gonadal tissues. These findings support the use of fin biopsies as a non-lethal method for assessing ageing biomarkers in the gonads of small freshwater fish.

Animals

Reproduction on the Rocks: Life History of a Freshwater Macrobioeroding Bivalve.

Macrobioerosion, the excavation and removal of consolidated mineral substrates by macrofauna, is well established in marine systems, where macrobioeroders drive carbonate cycling, sediment production and habitat formation. In freshwater ecosystems, however, it has been documented in only a small number of invertebrate taxa and remains a poorly resolved ecological process. Among these, the teredinid shipworm Lithoredo abatanica represents a remarkable departure from the wood-boring ecology of its family, having evolved to excavate and ingest limestone in fresh water. Despite this remarkable ecological transition, its reproductive biology and life history remain unknown. Here, we investigate the reproductive mode and life history strategy of this species using population size structure, in&#xa0;situ observations of siphonal morphology, and sperm morphometrics. We show that L.&#x2009;abatanica reaches exceptional dimensions, with measured body lengths exceeding 100&#x2009;mm, one intact empty burrow exceeding 200&#x2009;mm and in-water observations indicating burrows possibly exceeding 500&#x2009;mm, establishing it as the largest known freshwater macrobioeroder. Its large size and dense aggregations indicate considerable capacity for local rock breakdown and habitat modification within the Abatan River system (Bohol, Philippines). Recently settled juveniles (<&#x2009;10&#x2009;mm) alongside reproductively mature individuals indicate ongoing recruitment. The morphology of the siphons and calcareous tube appears to preclude direct sperm transfer via pseudocopulation, while sperm morphometrics are consistent with external fertilisation. Together, these findings indicate that L.&#x2009;abatanica reproduces via broadcast spawning with external fertilisation and likely possesses a planktotrophic larval phase. This raises a fundamental question: how does a broadcast-spawning species with planktotrophic larvae maintain populations up to 15&#x2009;km upstream in a flowing freshwater river subject to persistent downstream advection? By resolving the life history of the largest known freshwater macrobioeroder, this study provides critical insight into the persistence, dispersal and ecological role of a globally unique riverine ecosystem engineer.

broadcast spawning

Effects of faba bean-based crisping culture on phenotypic characteristics, muscle quality, and serum metabolome in Nile tilapia: Screening biomarkers to assess the degree of crisping.

Feeding Nile tilapia (Oreochromis niloticus) a faba bean-based crisping diet enhances muscle hardness (crispness) and overall flesh quality. However, the underlying mechanisms and reliable biomarkers remain insufficiently defined. This study integrated phenotypic traits, muscle texture, collagen content, serum antioxidant enzyme activities (SOD, CAT, and GSH-Px), MDA levels, and serum metabolomics to understand the determinants of muscle crisping. Fish were assigned to a crisping diet or a control group for 90&#xa0;days. Individuals in the crisping group were implanted with passive integrated transponder (PIT) tags to enable correlation analyses among phenotypic traits (body weight/length/frame changes), serum indicators (NAM, FAD, and GSH-Px) and muscle hardness. Compared with controls, the crisping diet significantly increased muscle hardness, gumminess, and chewiness, accompanied by elevated collagen content. Antioxidant profiles were altered, with higher activities of serum SOD and CAT, together with elevated MDA levels and reduced GSH-Px activity (P&#xa0;<&#xa0;0.05). Metabolomic analysis identified 830 differential metabolites (682 upregulated and 148 downregulated), predominantly comprising carboxylic acids and derivatives, glycerophospholipids, and benzene derivatives. Enrichment analysis indicated significant involvement in general metabolic pathways, ATP-binding cassette (ABC) transporters, amino acid biosynthesis, and glycine, serine, and threonine metabolism (P&#xa0;<&#xa0;0.05). Notably, acetylpyruvate was upregulated in glutathione metabolism, nicotinate and nicotinamide metabolism, and galactose metabolism; pantothenic acid was upregulated in glycine, serine, and threonine metabolism; whereas &#x3b4;-tocotrienol was downregulated. Correlation analysis revealed weak negative associations between muscle hardness and phenotypic traits (body weight/length/frame changes D5-7, D5-10, D7-8) (P&#xa0;<&#xa0;0.05). In contrast, serum NAM and FAD were weakly positively correlated with muscle hardness, whereas GSH-Px showed a weak negative correlation (P&#xa0;<&#xa0;0.05). Collectively, these findings suggest that body weight, body length, frame measurements (D5-7, D5-10, and D7-8), and serum NAM, FAD, and GSH-Px are associated with the degree of muscle crispness in Nile tilapia fed a faba bean-based crisping diet and may serve as candidate biomarkers under these culture conditions.

Animals

The SELENOP Polymorphism rs7579 Predicts Hepatic Steatosis in Females With Insulin Resistance in the General Population.

CONTEXT: Selenoprotein P is a hepatokine associated with several metabolic processes. Rs7579 (C > T) is a SeP-related functional single nucleotide polymorphism. OBJECTIVE: In this study, we aimed to identify the environmental factors affecting the relationship between rs7579 and metabolic diseases, such as metabolic dysfunction-associated steatotic liver disease, in the general population. METHODS: This cross-sectional study was based on the Shika Study, a survey of residents in the Noto Peninsula of Ishikawa Prefecture. We analyzed a total of 900 adults, measuring full-length selenoprotein P (FL-SeP) serum levels using a sol-particle homogeneous immunoassay. RESULTS: We observed that selenium and FL-SeP serum levels were associated with dyslipidemia. In males, serum selenium was associated with dyslipidemia and hepatic steatosis. However, in females, FL-SeP tended to be associated with diabetes. Participants carrying the TT genotype and hepatic steatosis exhibited higher levels of liver enzymes, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), and the homeostasis model assessment of &#x3b2;-cell function than those without hepatic steatosis or with other genotypes. In females carrying the TT genotype of rs7579, hepatic steatosis, hypertension, diabetes, obesity, and metabolic syndrome were associated with higher HOMA-IR levels. CONCLUSION: In this study, we revealed that the association between metabolic diseases and HOMA-IR differed single nucleotide polymorphism genotype and sex dependently. In females carrying the TT genotype of rs7579, hepatic steatosis-associated metabolic disorders (diabetes, hypertension, obesity, and metabolic syndrome) were associated with higher HOMA-IR. The results of this study open the way to genetic signatures-based personalized preventive medicines.

CCDC152

Estimation Model of Pig Weight Based on Body Measurements and Analysis of Its Genetic Basis.

Body weight and body measurements are key indicators of growth and economic efficiency in pigs, but conventional weighing is labor-intensive and stressful, increasing disease risk and necessitating non-contact estimation. We measured five dimensions (body length, chest circumference, abdominal circumference, body width, and body height) in 811 Suzi black pigs and constructed six multiple linear regression models using different combinations. All models had R2&#x2009;>&#x2009;0.91, with adjusted R2 also exceeding 0.91, and the model combining length, chest, and abdominal circumference gave the lowest RMSE, balancing accuracy and practicality. Separately, we performed GWAS on 165 genotyped individuals (100&#x2009;K SNP chip and GBS) for age (as a growth rate proxy), body weight, and the five measurements. No SNP reached genome-wide significance (p&#x2009;<&#x2009;1.86&#x2009;&#xd7;&#x2009;10-6), but three suggestive loci (p&#x2009;<&#x2009;1.39&#x2009;&#xd7;&#x2009;10-5) were detected: SNP 4_12&#x2009;319&#x2009;200 for age (35.55% variance), a pleiotropic SNP 1_60&#x2009;912&#x2009;826 associated with length, chest, and abdominal circumference (42.10%, 53.06%, and 45.97% variance), and SNP 1_60&#x2009;638&#x2009;159 for abdominal circumference. Positional mapping identified EPHA7 as the nearest candidate gene. Enrichment analyses revealed focal adhesion, receptor tyrosine kinase, IgSF-CAM, integrin, and PI3K-Akt pathways, with EPHA7 and FYN as key regulators. Notably, the three traits in the best model mapped to the same pleiotropic locus, suggesting a shared genetic basis. This study provides a practical estimation tool and suggestive markers, supporting non-contact weighing systems and molecular breeding.

Animals

An Immunosenescent CD8+ T Cell Subset in Patients with Axial Spondyloarthritis and Psoriatic Arthritis Links Spontaneous Motility to Telomere Shortening and Dysfunction.

OBJECTIVE: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA). METHODS: Peripheral blood CD8+ and CD4+ T cells were isolated from patients with r-axSpA (n = 128), PsA (n = 60), and rheumatoid arthritis (RA) (n = 74) and healthy donors (HDs) (n = 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA sequencing analysis, whereas telomere length and dysfunction were measured by reverse transcriptase-polymerase chain reaction and immunofluorescence-fluorescence in situ hybridization, respectively. RESULTS: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared with HDs and patients with RA. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (tumor necrosis factor), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response activation, telomere shortening, and dysfunction. CONCLUSION: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in patients with SpA that represents a possible player in disease pathogenesis.

Humans

Genome-Wide Association Analysis for Growth-Related Traits in Indoor- and Outdoor-Cultured Juvenile Grass Carp (Ctenopharyngodon idella).

Grass carp is a key herbivorous freshwater fish, yet long-term inbreeding reduces growth rates. Current genome-wide association studies (GWAS) primarily focus on a limited range of growth traits, while intestinal morphology is likely to emerge as a promising new proxy for both growth performance and health status. We reared juvenile grass carp from one batch in indoor vs. natural aquatic vegetation groups for 100 days, measuring body weight (BW), length (BL), height (BH), and intestinal length (IL) in 200 individuals (100/group). Phenotypic differences were significant for all traits, with IL most variable. GWAS identified 95 significant SNPs, among which 21 were related to multiple traits. Candidate gene and KEGG pathway analyses linked these SNPs to myogenesis, skeletal development, immunity, calcium signaling, and stress resistance. Twelve SNPs were found to be associated with IL, including 8 multi-trait-related and 4 trait-specific ones. This suggests that IL can serve as a supplementary growth trait. There was no overlap with prior GWAS, but recurrent signals on chromosomes 1, 2, 14 (BW) and 2, 3, 14, 24 (BH) merit further study. Our findings enrich molecular resources for grass carp and highlight IL's potential for marker-assisted breeding.

Ctenopharyngodon idella

Dynamic Evolution of Poly-A Tail Lengths Visualized by RNAse H Assay and Northern Blot Using Nonradioactive Probes in Yeast.

Poly-A tail length dynamics have been extensively studied from yeast to human, mostly using reporter transcripts. Recent studies have been carried out genome-wide to determine the status of poly-A tails at steady state. However, poly-A tail measurement at equilibrium gives an overall length that reflects a mixture of the different poly-A tail sizes for a single transcript. New genome-scale techniques are emerging to estimate dynamic of poly-A tails lengths, but they are not yet routine and individual validation experiments are useful. In this chapter we describe a protocol for visualizing poly-A tail lengths following transcription inhibition for a reporter mRNA using denaturing poly-acrylamide gel electrophoresis and northern blot assay. This protocol is quick to set up, requires the purchase of only a few specific reagents, does not rely on radioactivity for RNA monitoring, and can be easily implemented in any molecular biology laboratory.

Poly A

Concomitant telomere attrition is associated with spinal muscular atrophy in highly inbred region of North India: unraveling the thread in Kashmir region.

Spinal muscular atrophy (SMA) is a rare genetic disorder that unequivocally results in the degeneration of motor neurons, leading to muscle weakness and atrophy. This condition is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which inevitably results in a deficiency of the SMN protein. In present study, we investigated the potential role of telomere attrition in SMA patients. Relative telomere length in peripheral blood lymphocytes was measured by Monochrome Multiplex Quantitative Polymerase Chain Reaction (MMQPCR) in 98 subjects and we conclusively found that SMA cases exhibit telomere attrition compared to healthy controls (P&#x2009;=&#x2009;4&#x2009;&#xd7;&#x2009;10-&#x2009;2). Moreover, significant attrition was also observed in severe form of SMA, i.e. SMA type 0 (P&#x2009;=&#x2009;0.04) as well.Although, the exact mechanism through which telomere shortening contributes to the pathogenesis of SMA is not fully understood and is yet to be delineated. However, one possibility is that telomere shortening leads to genomic instability and DNA damage, which can contribute to motor neuron degeneration. Another possibility is that telomere shortening leads to cellular senescence, which can impair the ability of motor neurons to regenerate and repair themselves. Recent studies have suggested that telomere shortening may be a potential therapeutic target in SMA. Thus, understanding the role of SMN1 gene in disease pathogenesis & its effect on telomere length will aid in estimating the risk & prognosis of SMA in genetically less explored & highly inbred region of Kashmir, Northern India.

Humans

Phylogenomic subsampling and upsampling for efficient evolutionary analyses of big data.

Long runtimes, high memory demands, and reliance on high-performance computing impede phylogenomic analyses. We review a scalable phylogenomic subsampling with upsampling (PSU) framework to address this challenge, which reduces runtime and memory requirements by orders of magnitude. In PSU, small subsamples of sites from a concatenated alignment are analyzed, which are expanded by upsampling before inference, and the resulting inferences are aggregated to obtain evolutionary estimates. PSU harnesses the fact that the computational cost of maximum likelihood analysis is strongly influenced by the number of distinct site patterns in the concatenated alignment, whereas statistical power depends primarily on the amount of evolutionary information represented by the total number of sites and substitutions. By reducing the former while restoring the latter through upsampling, PSU can approximate many full-alignment analyses at substantially lower computational cost. Analysis of simulated and empirical datasets shows that PSU can accurately estimate bootstrap support values, select the optimal substitution model, test evolutionary hypotheses, and infer branch lengths, divergence times, and associated uncertainty measures. PSU also provides distributions of inferred clade support across independent subsamples, enabling detection of conflicting phylogenetic signals that may remain hidden in conventional bootstrap analysis of concatenated alignments. Automated tuning of subsample size, the number of subsamples, and the number of upsampling replicates make PSU practical. We suggest that PSU is a general approach for scalable phylogenomic inference using a broad range of statistical methods. By enabling analyses of genome-scale alignments on commodity hardware, PSU broadens research access and reduces environmental and infrastructural costs of big-data phylogenomics.

Phylogeny

Effects of Vacuum Compression Therapy on Healing of Chronic Lower Limb Ulcers: A Randomised Controlled Study.

Chronic lower limb ulcers remain difficult to manage when unresponsive to conventional treatment. This study evaluated the clinical and physiological effects of vacuum compression therapy on wound healing and quality of life. Fifty patients with chronic lower limb ulcers were randomised to receive 12 sessions of vacuum compression therapy plus standard care or standard care alone over 4&#x2009;weeks. Wound dimensions, exudate, pain intensity and quality of life were assessed at baseline and post-treatment. Estimated wound volume was calculated as length&#x2009;&#xd7;&#x2009;width&#x2009;&#xd7;&#x2009;depth. Tissue oxygenation was measured at the dorsum of the foot in the experimental group. The vacuum compression therapy group showed greater improvements in wound width, depth, volume and quality of life. Estimated wound volume decreased by 61% in the intervention group, whereas no statistically significant volume reduction was observed in controls. Local tissue oxygenation in the experimental group increased by 43%. Baseline wound size was associated with poorer quality of life. Vacuum compression therapy may enhance wound healing and quality of life in patients with chronic lower limb ulcers. Observed increases in local tissue oxygenation represent exploratory physiological findings within the treated cohort that warrant controlled comparative evaluation. Trial Registration: ClinicalTrials.gov identifier: NCT07737184.

Humans

Phylogenomic subsampling and upsampling for efficient evolutionary analyses of big data.

Long runtimes, high memory demands, and reliance on high-performance computing impede phylogenomic analyses. We review a scalable phylogenomic subsampling with upsampling (PSU) framework, in which small subsamples of sites from a concatenated alignment are expanded by upsampling before inference, and the resulting analyses are then aggregated to obtain evolutionary estimates. PSU harnesses the fact that the computational cost of maximum likelihood analysis is strongly influenced by the number of distinct site patterns in the concatenated alignment, whereas statistical power depends primarily on the amount of evolutionary information represented by the total number of sites and substitutions. By reducing the former while restoring the latter through upsampling, PSU can approximate many full-data analyses at substantially lower computational cost. Analysis of simulated and empirical datasets shows that PSU can accurately estimate bootstrap support values, select the optimal substitution model, test evolutionary hypotheses, and infer branch lengths, divergence times, and associated uncertainty measures, while reducing runtime and memory requirements by orders of magnitude. PSU also provides distributions of inferred clade support across independent subsamples, enabling detection of conflicting phylogenetic signals that may remain hidden in conventional bootstrap analysis. Automated tuning of subsample size, the number of subsamples, and the number of upsampling replicates make PSU practical across diverse datasets. We suggest that PSU is a general strategy for scalable phylogenomic inference using a broad range of statistical methods. By enabling analyses of genome-scale alignments on commodity hardware, PSU broadens research access and reduces environmental and infrastructural costs of big-data phylogenomics.

confidence limits

A Sentiment-Based Comparison of AI- and Physician-Generated Empathic Statements in Palliative Care.

CONTEXT: Empathic communication promotes trust in patient-provider relationships. As healthcare integrates artificial intelligence (AI) into patient communication, we have yet to understand how these models' communication compares to that of physicians. OBJECTIVES: Our primary objectives were to examine patient preferences for AI-generated vs. palliative care physician-generated empathic statements addressing fear and anxiety around cancer treatment, and to analyze associations between linguistic features and patient preferences. METHODS: We conducted a secondary analysis of the PALL-AI trial, a randomized controlled survey comparing cancer patients' preferences of AI- to physician-generated empathic statements. Physicians and AI were provided the same prompt with a maximum sentence length. Patient preferences for each statement were measured in blinded surveys. We analyzed sentiment of the statements using the Valence Aware Dictionary and Sentiment Reasoner (VADER) and the National Research Council Canada (NRC) Emotion Lexicon. We evaluated associations between sentiment scores and patient preferences using Spearman's correlation coefficients. RESULTS: A total of 105 patients completed blinded surveys, preferring the AI-generated statement 72.4% of the time. VADER sentiment analysis showed all three AI statements displayed positive sentiment, while all three physician statements displayed negative sentiment. Controlling for statement length, AI statements used twice as many positive words as human statements. However, they contained a similar number of negative words. Of the eight NRC emotions, "trust" and "joy" demonstrated the strongest correlations with patient preference. CONCLUSION: Patients preferred AI-generated statements around cancer care over those from palliative care physicians when standardized for prompt and statement length. Analysis shows AI-generated statements contain more positive language which may be the factor driving patient preference toward AI.

Humans