Degree Of Heterogeneity Research Articles

Pore Structure and Heterogeneity in the Lacustrine Shale of the Second Member of the Paleogene Funing Formation, Subei Basin, China

Characterization of pore structure and heterogeneity is crucial for exploring and evaluating shale oil and gas resources. Existing methodologies exhibit various limitations, and intuitive, quantitative description techniques are lacking. To address these issues, shales from the second member of the Funing Formation (E1f2) in the Subei Basin were studied in this study. A comprehensive research methodology was employed that combined petrological analysis, physical structure testing, and SEM images supplemented with multifractal analysis and partial least squares regression (PLSR) data processing to achieve nuanced qualitative and quantitative characterization of the heterogeneity in lacustrine shale pore structures. This study revealed that E1f2 shale pores predominantly consist of mesopores (2–50 nm) and macropores (>50 nm). A positive correlation was observed between the development of mesopores and calcite content, while a negative correlation exists with orthoclase content. Conversely, a positive correlation with plagioclase content was found in macropore development. The growth in total pore volume is inhibited by the total organic carbon (TOC) content. Employing multifractal methods to analyze pore morphology data extracted from scanning electron microscopy (SEM) images facilitated a quantitative characterization of the heterogeneity within the pore structures. The results showed that organic-medium mixed shale (OMMS) has the strongest heterogeneity. The weakest heterogeneity is exhibited by the organic-medium calcareous shale (OMCS). PLSR analysis indicates that the structural heterogeneity of the E1f2 shales is positively correlated with TOC content and negatively correlated with orthoclase content. Additionally, the type of pore influences the degree of heterogeneity. Increasing the total and macropore volume reduces the heterogeneity, while increasing the micropore (<2 nm) volume enhances it in the E1f2 shales.

Academic and Community Hospitals differ in stroke subtype classification and cardiac monitoring: the DiVERT multi-center cohort study

BackgroundCardiac monitoring strategies to detect occult atrial fibrillation (AF) post-stroke differ among healthcare institutions. This may be related to discrepancies in stroke subtype classification/adjudication, and/or consultation of cardiology specialists at Community Hospitals (CoH) and Academic Centers (AcC). Identifying the degree of heterogeneity may encourage development of guideline-directed monitoring protocols, result in higher AF detection rates and treatments, and fewer strokes.MethodsThe DiVERT (SeconDary Stroke PreVEntion ThRough Pathway ManagemenT) study was designed to characterize post-stroke cardiac monitoring practices in a hospital setting. Care pathways were assessed with in-person stakeholder interviews; patient-level data were reviewed using electronic medical records.ResultsDiVERT identified 2,475 patients with diagnoses of cryptogenic (83.6% vs. 33.1%, p < 0.001), large vessel disease (LVD) (13.3% vs. 37.0%, p < 0.001), or small vessel disease (SVD) (3.1% vs. 29.9%, p < 0.001) stroke, at CoH and AcC, respectively. CoH consulted cardiology significantly less than AcC (12.3% vs. 34.7%, p < 0.001) and ordered significantly fewer short- or long-term cardiac monitors than AcC (6.8% vs. 69.2%, p < 0.001). CoH had shorter length of stay (5.3 vs. 9.4 days, p < 0.001) and patient demographics were significantly different (p < 0.001 for age, ethnicity and race).ConclusionSignificant heterogeneity in cardiac monitoring post-stroke exists: CoH reported 2.5-times more cryptogenic stroke than AcC yet ordered 10-times fewer short/long-term cardiac monitors to look for AF. Significant differences in patient demographics among institutions may account for this discrepancy. Regardless, efforts to reduce heterogeneity are warranted to improve AF detection and treatment and prevent recurrent stroke.

Effects of suspension exercise training in the treatment of lumbar disk herniation: a systematic review and meta-analysis

ObjectiveThe study aimed to systematically evaluate the efficacy of suspension exercise training (SET) in the treatment of lumbar intervertebral disk herniation and provide a scientific basis for clinical treatment.MethodsDatabases such as CNKI, Chinese Wanfang, PubMed, Cochrane, the Web of Science, and Embase were searched up to June 2024. A quality assessment was performed using the Cochrane Collaboration’s risk-of-bias guidelines, and a meta-analysis was conducted using RevMan 5.4 and Stata 17.0.ResultsA total of 11 studies involving 943 patients were included. Suspension exercise training significantly improved the lumbar disk herniation (LDH) visual analog scale (VAS) score (mean difference (MD) = −0.96; 95% confidence interval (CI), −1.10 to-0.82; p < 0.00001, I2 = 23%), the Japanese Orthopedic Association (JOA) score (MD = 3.29, 95% CI, 1.67 to 4.90; p < 0.0001, I2 = 92%), and the Oswestry Disability Index (ODI) score (MD = −5.41, 95% CI, −7.41 to −3.40; p < 0.00001, I2 = 86%). Subgroup analysis of the JOA score showed better efficacy with suspension exercise training combined with traditional Chinese medicine (TCM) (MD = 4.29, 95% CI, 2.73 to 5.86; p < 0.00001, I2 = 80%) compared to suspension exercise training combined with non-TCM (MD = 0.96, 95% CI, 0.49 to 1.43; p < 0.0001, I2 = 0%).ConclusionSuspension exercise training significantly improved the VAS score, JOA score, and ODI score of the patients with lumbar disk herniation; however, there was a high degree of heterogeneity in the JOA score and ODI score. Further validation is needed in the future for different populations with lumbar disk herniation, the specific locations of its occurrence, and the combined modality of suspension exercise training.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024554074.

Promotion of cooperation in a structured population with environmental feedbacks.

Cooperation is a representative altruistic behavior in which individuals contribute public goods to benefit their neighborhoods and even larger communities in social networks. The defective behavior is more likely to bring higher payoffs than the cooperative behavior, which makes the cooperative behavior hard to maintain and sustain. Many mechanisms were proposed to promote cooperation within a social dilemma, in which some recent studies introduced the impact of dynamically changing environments on players' payoffs and strategies in social-ecological systems, and evolutionary-ecological systems. However, degree heterogeneity, an important structural property of many real-world complex networks such as social networks, academic collaboration networks, and communication networks, is rarely explored and studied in such eco-evolutionary games. In this research, we propose a Public Goods Game model on social networks with environmental feedback and analyze how the environmental factor and network structure affect the evolution of cooperation. It is found that as the initial environmental factors and the cooperation-enhancement defection-degradation ratio increase, the steady cooperation level of the social network significantly increases, and the dynamic environment will eventually evolve into a high-return environment; On the other hand, even if the initial environmental benefit coefficient is high, when the cooperation-enhancement defection-degradation ratio is less than a threshold, the dynamic environment will gradually degrade into a low-return environment. The steady cooperation level of the social network first gradually increases as the network structure becomes more heterogeneous, but it will decrease once the heterogeneity of the social network exceeds a certain threshold.

Outcome Reporting in Prospective Studies Evaluating Neurostimulation for Obstructive Sleep Apnea.

Due to the controversy surrounding the appropriate outcomes in neurostimulation, we sought to systematically describe ways in which polysomnography and apnea-hypopnea index are reported in prospective studies involving unilateral hypoglossal nerve stimulation. MEDLINE (Ovid), Embase (Ovid), Cochrane Library, and Scopus. Following the Preferred Reporting items of Systematic Reviews and Meta-analysis (PRISMA) Statement guidelines, a systematic two-reviewer system was used for study screening and quality assessment. Articles that met inclusion criteria were included. Quality was evaluated with either the Newcastle-Ottawa Quality Assessment Scale or the Covidence risk-of-bias tool. Fifteen studies met the inclusion criteria, which included 14 prospective cohort studies and one randomized controlled trial. Titration polysomnography was the primary sleep study used to acquire data in five of the studies compared to only three studies employing exclusively non-titration polysomnography to report outcomes. Three studies compiled data from two or more sleep studies to report a single apnea-hypopnea index. Within the 15 studies, non-titration apnea-hypopnea index was the most reported type (five studies). Titration apnea-hypopnea index was used to report outcomes in one study. Five studies did not specify what type of apnea-hypopnea index was employed to report treatment effectiveness. The reported sleep studies and corresponding apnea-hypopnea indices were highly variable across the studies. Because of the high degree of heterogeneity, future research would benefit from consistent use of a standardized apnea-hypopnea index to report outcomes related to hypoglossal nerve stimulation. NA Laryngoscope, 134:4873-4881, 2024.

The Incidence of Infection Following Open Tibia Fractures in Low-Income Countries: A Systematic Review

Introduction: Open tibial fractures (OTFs) are common in low-income countries (LICs), primarily caused by road traffic collisions. High rates of infection in OTFs contribute to prolonged recovery, disability, and economic loss. Identifying infection rates and causative organisms is essential for improving outcomes and guiding antibiotic treatment in LICs. This systematic review aimed to determine the incidence of surgical site infections (SSIs) following OTF treatment in LICs and identify the most prevalent microorganisms involved. Methods: Following PRISMA and Cochrane guidelines, a systematic review was conducted using five databases. Eligible studies included randomised controlled trials, cohort studies, and case series investigating OTFs in LICs. Studies with fewer than ten participants, military medical resources, or those from high-income countries were excluded. Data were extracted for infection rates, causative organisms, and treatment modalities, with a meta-analysis performed using a random effects model to calculate incidence in person-years. Results: Five studies, including two retrospective cohorts, two prospective cohorts, and one RCT, were analysed. The overall infection incidence was 23.21 per 100 person-years (95% CI: 9.19; 58.62). Subgroup analysis showed a slightly lower incidence of 21.88 per 100 person-years for surgical interventions. A high degree of heterogeneity (I² = 91%) was noted. Common causative organisms were not consistently reported. Conclusion: The incidence of SSIs following OTFs in LICs is high, particularly in severe fractures. Establishing a baseline infection rate is critical for future studies to evaluate treatment efficacy and improve outcomes in resource-limited settings. Further research should focus on standardising definitions and reporting of infections to reduce heterogeneity.

Feasibility, acceptability and prognostic value of muscle mass and strength measurement in patients with hip fracture: a systematic review.

Sarcopenia is diagnosed on the basis of low muscle strength, with low muscle mass used to confirm diagnosis. The added value of measuring muscle mass is unclear. We undertook a systematic review to assess whether muscle mass measurement in patients with hip fracture was acceptable, feasible and independently associated with adverse outcomes. Electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov) were searched for studies of patients with hip fracture aged ≥ 60 with perioperative muscle mass or strength assessments. Associations with postoperative outcomes including death, length of stay and activities of daily living were extracted. Risk-of-bias was assessed using the AXIS and ROBINS-I tools. Due to the degree of study heterogeneity, data were analysed by narrative synthesis. The search strategy identified 3317 records. 36studies were included with 7860 participants. Acceptability ofmuscle mass measurement was not assessed, but measurement appeared feasible using biompedance, dual energy x-ray absorptiometry and computed tomography. Univariate analyses indicated that lower muscle mass was associated with higher death rates at 30days, worse mobility, worse activity of daily living metrics and worse physical performance but there was no significant association with length of stay or postoperative complications. Four studies included both muscle mass and strength in multivariable analyses; muscle mass was a significant independent predictor of only one adverse outcome in a single study after adjustment for muscle strength and other predictor variables. Current data suggest that muscle mass assessment offers no additional prognostic information to muscle strength measures in patients with hip fracture.

Commuter choice of UAM-friendly neighborhoods

Urban Air Mobility (UAM) which provides swift intra- and intercity transportation services has the potential to induce shifts in individuals’ commuting and residential decisions. It is anticipated that, in residential areas, UAM services would enhance accessibility for residents. An UAM-friendly neighborhood represents a novel, integrated neighborhood concept that provides the infrastructure and travel environment required to facilitate UAM services, thereby promoting sustainable neighborhood development and improving accessibility. To gain a deeper understanding of commuters’ choice behavior in UAM-friendly neighborhoods, we designed a stated choice experiment. Using data collected in Beijing city, we estimated a mixed logit model with interaction effects to identify the choice preferences of different people while capturing the unobserved preference heterogeneity. We found that individuals generally prefer to reside in such neighborhoods where the access distance to UAM vertiports is within one kilometer, the parking fee is either low (5 yuan/day) or free, the commuting time by UAT is 15 min, and drone window-docking delivery services are available. Households with high incomes (>400,000 yuan/year) and those owning a car are likely to adopt these novel neighborhoods. There is a varying degree of heterogeneity observed regarding residential location and distance to UAM vertiports among individuals in different age groups. Results of the elasticity analysis indicate that UAT commuting cost has the greatest impact on the likelihood of residing in UAM-friendly neighborhoods.

Scaling law for correcting the gravel content effect due to scalping techniques by DEM investigations

Scalping techniques are commonly employed to handle oversized particles in gravelly soils for performing laboratory tests, which will cause significant gravel content (GC) effect on the predicted mechanical behaviors of prototype soils. To solve this obstacle, this study tries to establish the scaling law for correcting the GC effect, which controls the same equivalent skeleton void ratio between the prototype and model soils. The proposed scaling law characterizes the mechanical parameters using the newly introduced indexes including the degree of heterogeneity and the scaling factor for parameter A of the Harding equation. Then a series of DEM simulations of element tests were performed on sand-dominant gravelly soils to parameterize and check the applicability of the proposed scaling law. The simulation results show that both the converted shear responses and shear modulus reduction curves through the proposed scaling law are highly consistent with that of the prototype soils. This suggests that in dealing with deformation problems from small to medium strains, Rocha’s assumption is highly applicable for correcting the GC effect. When the adopted scalping techniques control the change in GC (ΔGC) below 20 %, the predicted liquefaction resistance will be very close to that of the prototype soils regardless of the earthquake magnitudes. However, when ΔGC is larger than 40 %, the prediction error in liquefaction resistance will be larger. Based on these simulation results, it is recommended that when selecting scalping techniques for laboratory tests on gravelly soils containing oversized particles, it is preferred that ΔGC be kept below 20 %.

Deformation pseudo-twinning of the L21-ordered intermetallic superlattice

Ordered intermetallic materials are promising candidates for applications in extreme environments due to the strong localized bonding schemes that stabilize the structures against degradation. Here, we investigate the propensity for deformation twinning modes in the L21-ordered MnCu2Al intermetallic by inducing a state of severe plastic deformation. Post-mortem microstructural analysis reveals the presence of meso-scale deformation twins accompanied by a high degree of nano-scale crystalline heterogeneity. The orientation relationship between the parent and twin structures is consistent with activation of the 〈111〉{112} deformation twinning mode. Ab initio generalized stacking fault energy curve calculations corresponding to 〈111〉{112} twinning shear suggest that the magnitude of the twinning partial is 14〈111〉{112} and results in the local formation of a metastable orthorhombic phase within the pseudo-twin. This work highlights the discrepancy between the deformation modes of ordered/disordered structures and promotes an increased awareness for the role that long-range chemical order plays in determining deformation modes.

Time-varying Macro-Financial Linkages across Developed Countries

The paper examines time-varying linkages between the financial and macroeconomic sectors across 13 developed countries. To do so, the paper studies whether the financial sector is an important source of shock to the macroeconomic sectors across countries. The paper finds evidence of time-varying impacts of the financial shocks on the macroeconomic sectors across countries. There are evidence of time variation in both the transmission and the size of the shocks. Different financial shocks play important roles in different financial shocks. For instance, The US house-price shock plays an important role in the Global Financial Crisis. The model also captures the large degree of heterogeneity in the effect of a financial shock across countries.

Structure of the human TSC:WIPI3 lysosomal recruitment complex.

Tuberous sclerosis complex (TSC) is targeted to the lysosomal membrane, where it hydrolyzes RAS homolog-mTORC1 binding (RHEB) from its GTP-bound to GDP-bound state, inhibiting mechanistic target of rapamycin complex 1 (mTORC1). Loss-of-function mutations in TSC cause TSC disease, marked by excessive tumor growth. Here, we overcome a high degree of continuous conformational heterogeneity to determine the 2.8-Å cryo-electron microscopy (cryo-EM) structure of the complete human TSC in complex with the lysosomal recruitment factor WD repeat domain phosphoinositide-interacting protein 3 (WIPI3). We discover a previously undetected amino-terminal TSC1 HEAT repeat dimer that clamps onto a single TSC wing and forms a phosphatidylinositol phosphate (PIP)-binding pocket, which specifically binds monophosphorylated PIPs. These structural advances provide a model by which WIPI3 and PIP-signaling networks coordinate to recruit TSC to the lysosomal membrane to inhibit mTORC1. The high-resolution TSC structure reveals previously unrecognized mutational hotspots and uncovers crucial insights into the mechanisms of TSC dysregulation in disease.

Association of epigenetic landscapes with heterogeneity and plasticity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Due to a lack of clear symptoms, patients often present with advanced disease, with limited clinical intervention options. The high mortality rate of PDAC is, however, also a result of several other factors that include a high degree of heterogeneity and treatment resistant cellular phenotypes. Molecular subtypes of PDAC have been identified that are thought to represent these cellular phenotypes at the tissue level. The epigenetic landscape is an important factor that dictates these subtypes. Permissive epigenetic landscapes serve as drivers of molecular heterogeneity and cellular plasticity in developing crypts as well as metaplastic lesions. Drawing parallels with other cancers, we hypothesize that epigenetic permissiveness is a potential driver of cellular plasticity in PDAC. In this review will explore the epigenetic alterations that underlie PDAC cell states and relate them to cellular plasticity from other contexts. In doing so, we aim to highlight epigenomic drivers of PDAC heterogeneity and plasticity and, with that, offer some insight to guide pre-clinical research.

Neuronal heterogeneity of normalization strength in a circuit model.

The size of a neuron's receptive field increases along the visual hierarchy. Neurons in higher-order visual areas integrate information through a canonical computation called normalization, where neurons respond sublinearly to multiple stimuli in the receptive field. Neurons in the visual cortex exhibit highly heterogeneous degrees of normalization. Recent population recordings from visual cortex find that the interactions between neurons, measured by spike count correlations, depend on their normalization strengths. However, the circuit mechanism underlying the heterogeneity of normalization is unclear. In this work, we study normalization in a spiking neuron network model of visual cortex. The model produces a range of neuronal heterogeneity of normalization strength and the heterogeneity is highly correlated with the inhibitory current each neuron receives. Our model reproduces the dependence of spike count correlations on normalization as observed in experimental data, which is explained by the covariance with the inhibitory current. We find that neurons with stronger normalization are more sensitive to contrast differences in images and encode information more efficiently. In addition, networks with more heterogeneity in normalization encode more information about visual stimuli. Together, our model provides a mechanistic explanation of heterogeneous normalization strengths in the visual cortex, and sheds new light on the computational benefits of neuronal heterogeneity.

Cooperative SIR dynamics as a model for spontaneous blood clot initiation

Blood clotting is an important physiological process to suppress bleeding upon injury, but when it occurs inadvertently, it can cause thrombosis, which can lead to life threatening conditions. Hence, understanding the microscopic mechanistic factors for inadvertent, spontaneous blood clotting, in absence of a vessel breach, can help in predicting and averting such conditions. Here, we present a minimal model – reminiscent of the SIR model – for the initiating stage of spontaneous blood clotting, the collective activation of blood platelets. This model predicts that in the presence of very small initial activation signals, collective activation of the platelet population is possible, but requires a sufficient degree of heterogeneity of platelet sensitivity. To propagate the activation signal and achieve collective activation of the bulk platelet population, it requires the presence of, possibly only few, hyper-sensitive platelets, but also a sufficient proportion of platelets with intermediate, yet higher-than-average sensitivity. A comparison with experimental results demonstrates a qualitative agreement for high platelet signalling activity.

Characterization of Breast Cancer Intra-Tumor Heterogeneity Using Artificial Intelligence.

Intra-tumor heterogeneity (ITH) is a fundamental characteristic of breast cancer (BC), influencing tumor progression, prognosis, and therapeutic responses. However, the complexity of ITH in BC makes its accurate characterization challenging. This study leverages deep learning (DL) techniques to comprehensively evaluate ITH in early-stage luminal BC and provide a nuanced understanding of its impact on tumor behavior and patient outcomes. A large cohort (n = 2561) of early-stage luminal BC was evaluated using whole slide images (WSIs) of hematoxylin and eosin-stained slides of excision specimens. Morphological features of both the tumor and stromal components were meticulously annotated by a panel of pathologists in a subset of cases. A DL model was applied to develop an algorithm to assess the degree of heterogeneity of various morphological features per individual case utilizing defined patches. The results of extracted features were used to generate an overall heterogeneity score that was correlated with the clinicopathological features and outcome. Overall, 162 features were quantified and a significant positive correlation between these features was identified. Specifically, there was a significant association between a high degree of intra-tumor heterogeneity and larger tumor size, poorly differentiated tumors, highly proliferative tumors, tumors of no special type (NST), and those with low estrogen receptor (ER) expression. When all features are considered in combination, a high overall heterogeneity score was significantly associated with parameters characteristic of aggressive tumor behavior, and it was an independent predictor of poor patient outcome. In conclusion, DL models can be used to accurately decipher the complexity of ITH and provide extra information for outcome prediction.

Single-cell data revealed the regulatory mechanism of TNK cell heterogeneity in liver metastasis from gastric cancer

AimThe present work set out to classify cell subpopulations related to liver metastasis from gastric cancer (GC) and the mechanisms of their interactions with other immune cell subpopulations.BackgroundGC is characterized by a high degree of heterogeneity and liver metastasis. Exploring the mechanism of liver metastasis of GC from the perspective of heterogeneity of the tumor microenvironment (TME) might help improve the efficacy of GC treatment.ObjectiveBased on the cellular subpopulation characteristics of GC with liver metastasis, the regulatory mechanisms contributing to GC progression were analyzed, with special focuses on the roles of signaling pathways, transcription factors (TFs) and ligand–receptor pairs.MethodsThe GSE163558 dataset was downloaded from the Gene Expression Omnibus (GEO) database to collect single-cell transcriptomic data of GC patients and their metastasis groups for cell clustering and relevant analyses. Differentially expressed genes (DEGs) in the GC and GC liver metastasis groups were screened and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. SCENIC analysis was used to mine TFs that affected cellular subpopulations during liver metastasis from GC. The relative expression levels of TFs in GC were determined using qRT-PCR. Transwell and wound healing assays were utilized to verify the regulation of the TFs on the migration and invasion of GC cells. Interaction network between the cellular subpopulations was developed applying CellChat.ResultsSingle-cell clustering was performed to group six major cell subpopulations, namely, Myeloid cells, B cells, Mast cells, Epithelial cells, Fibroblasts, and TNK cells, among which the number of TNK cells was significantly increased in the GC liver metastasis group. Differentially enriched pathways of TNK cells between GC and GC liver metastasis groups mainly included IL-17 and Pi3k–Akt signaling pathways. TNK cell subsets could be further categorized into CD8 T cells, Exhausted T cells, NK cells, NKT cells, and Treg cells, with the GC liver metastasis group showing significantly more CD8 T cells and NKT cells. FOS and JUNB were the TFs of TNK cell marker genes that contributed to liver metastasis from GC and the invasion and migration of GC cell lines. Significant differences in immune cell communication ligand–receptor pairs existed between the GC and GC liver metastasis groups.ConclusionThis study revealed the critical role of TNK cell subsets in GC with liver metastasis applying single-cell transcriptomics analysis. The findings provided an important theoretical basis for developing novel therapies to inhibit liver metastasis from GC.

Abstract 4135968: Radiomic features of skeletal muscle on prostate T1-Weighted MRI associated with MACE outcomes in prostate cancer patients undergoing hormonal therapy

Background: Patients with high-risk prostate cancer (PC) who undergo hormonal therapy(HT) frequently die of major adverse cardiovascular events (MACE). Skeletal muscle on abdominal T1-weighted MRI (T1W) has been shown to be associated with cardiovascular fitness. Aims: To quantify heterogeneity associated with skeletal muscle tissue composition on prostate MRI patients undergoing HT using computationally derived radiomic features and identify their association with MACE. Methods: Cohort of N=58 men diagnosed with PC who underwent a 3 Tesla pre-treatment multi-parametric MRI followed by HT and followed up for MACE events were identified. MACE is defined as a composite of cardiovascular death, atrial fibrillation, myocardial infarction, ischemic stroke, heart failure, coronary artery disease, and peripheral vascular disease. Regions of interest (ROI) of skeletal muscle, including the obturator externus, pectineus, and the adductor group of muscles, were delineated on axial T1W under the guidance of an experienced radiologist. A set of 120 radiomic features, including gray level statistics, co-occurrence, wavelet, and texture energy-based features, were extracted within the ROI which quantifies underlying subvisual texture-based heterogeneity. Radiomics associated with MACE events were identified using the Wilcoxon rank-sum test and univariate Cox-regression (p<0.05). Results: Of the N=58 patients included in this study, 18 experienced MACE. The most common MACE event was AF (8.6%). Median-time-to-MACE event was 7.3 years (6.2-8.2). 3 radiomic features (Table 1) quantifying the heterogeneity of skeletal muscle on prostate T1W were observed to be associated with MACE. Specifically, we observe that first order features have a lower response and wavelet features have a lower response in MACE patients which suggests a higher degree of local deformations and heterogeneity in skeletal tissue compared to non-MACE patients. Conclusions: Results from our study suggest that radiomics quantified texture characteristics of skeletal muscle tissue may indicate cardiovascular fitness, reflecting the likelihood of experiencing MACE following initiation of HT in PC men. Pre-treatment identification of PC patients at high risk of MACE may allow for alternative treatment options improving cardiovascular outcomes. Future studies will involve exploring larger, multi-site cohorts and machine learning modeling to determine cardiovascular risk.

Causal links of human serum metabolites on the risk of prostate cancer: insights from genome-wide Mendelian randomization, single-cell RNA sequencing, and metabolic pathway analysis.

Recently, serum metabolites have shown potential in predicting survival outcomes and may be related to the pathogenesis of prostate cancer. Nevertheless, the precise impact concerning the genetic effect of metabolites on prostate cancer risk remains obscure. In this context, we conducted a Mendelian randomization (MR) study aiming to explore the causality between genetically determined metabolites and the risk of prostate cancer. We conducted a two-sample MR analysis aiming to identify the underlying metabolites associated with prostate cancer. Exposure information was obtained from the largest metabolome-based genome-wide association (GWAS) data containing 7,824 Europeans. Genome-wide association analysis was utilized to detect instrumental variables (IVs) for metabolites. We applied the inverse-variance weighted (IVW) approach as the primary method, and to augment the reliability and robustness of our findings, additional analysis methods encompassing weighted median, MR-Egger, and leave-one-out analysis were utilized. MR-Egger intercept test was implemented to explore the pleiotropy. Cochran's Q test was utilized to quantify the degree of heterogeneity. Additionally, we performed metabolic pathway analysis and single-cell RNA sequencing analysis. We found that three serum metabolites were causally associated with prostate cancer after utilizing rigorous screening standards. Utilizing single nucleotide polymorphisms as IVs, a 1-SD increase in fructose was associated with 77% higher risk of prostate cancer (OR:1.77, 95%CI: 1.05-2.97, PIVW=0.031), a 1-SD increase in N1-methyl-3-pyridone-4-carboxamide was associated with 29% higher risk of prostate cancer (OR:1.29, 95%CI: 1.05-1.58, PIVW=0.017), and a 1-SD increase in 12-hydroxyeicosatetraenoate (12-HETE) was associated with 18% higher risk of prostate cancer (OR:1.18, 95%CI: 1.07-1.31, PIVW=0.0008). Metabolites that were causally linked to the risk of prostate cancer were mainly enriched in the valine, leucine and isoleucine biosynthesis pathway (P=0.026) and the nicotinate and nicotinamide metabolism pathway (P=0.048). Our MR analysis provided suggestive evidence supporting the causal relationships between three identified serum metabolites and prostate cancer, necessitating further investigation to elucidate the underlying mechanisms through which these blood metabolites and metabolic pathways may impact the initiation and progression of prostate cancer.

Exploring the clinical potential of circulating LncRNAs in breast cancer: insights into primary signaling pathways and therapeutic interventions.

Breast cancer (BC) occupies the top spot among women on a global scale. The tumor has a significant degree of heterogeneity, displaying a notable prevalence of medication resistance, recurrence, and metastasis, rendering it one of the most lethal forms of malignant neoplasms. The timely identification, ongoing evaluation of therapeutic interventions, and accurate prediction of outcomes play crucial roles in determining the overall survival rates of women with BC. Nevertheless, the absence of precise biomarkers remains a significant determinant impacting the overall well-being and both the physical and emotional health of BC patients. Long noncoding RNA (lncRNA) exerts regulatory control over several genes and signaling pathways, hence assuming crucial roles in the development of neoplastic growth. Recently, research has indicated that the atypical expression of circulating lncRNAs in various biological bodily fluids has a noteworthy impact on the early detection, pathological categorization, staging, monitoring of therapy outcomes, and evaluation of prognosis in cases of BC. This article aims to assess the potential clinical utility of circulating lncRNAs in the context of BC focusing on specific primary signaling pathways; Wnt/β-catenin, Notch, TGF-β, and hedgehog (Hh), in addition to some therapeutic interventions.