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Confocal Raman microscopy of liquid-crystal-filled polymer capsules made by photo-enforced stratification.

The applicability of confocal Raman microscopy for characterizing thin liquid-crystal (LC) filled polymer capsules obtained by photo-enforced stratification is demonstrated. The investigated structure consists of an array of polymer capsules (typical size 500 x 500 x 20 microm) filled with LC material and is made by photopolymerization of a mixture of monomers and LC. Such an array can be used as the electro-optical component in liquid crystal displays. Confocal Raman microscopy does not require complex sample preparation, is non-invasive, and is shown to have adequate spatial and depth resolution. Although Raman spectroscopy is inherently insensitive, the use of data preprocessing and computational modeling makes it possible to quantify both the conversion of monomer to polymer and the compositions of both the polymer-rich and the LC-rich phase.

Journal Article↗

An integrative network approach for longitudinal stratification in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms resulting from the loss of dopamine-producing neurons in the brain. Currently, there is no cure for the disease which is in part due to the heterogeneity in patient symptoms, trajectories and manifestations. There is a known genetic component of PD and genomic datasets have helped to uncover some aspects of the disease. Understanding the longitudinal variability of PD is essential as it has been theorised that there are different triggers and underlying disease mechanisms at different points during disease progression. In this paper, we perform longitudinal and cross-sectional experiments to identify which data modalities or combinations of modalities are informative at different time points. We use clinical, genomic, and proteomic data from the Parkinson's Progression Markers Initiative. We validate the importance of flexible data integration by highlighting the varying combinations of data modalities for optimal stratification at different disease stages in idiopathic PD. We show there is a shared signal in the DNAm signatures of participants with a mutation in a causal gene of PD and participants with idiopathic PD. We also show that integration of SNPs and DNAm data modalities has potential for use as an early diagnostic tool for individuals with a genetic cause of PD.

Parkinson Disease↗

Graph neural network-based risk stratification of prostate cancer using gene expression and SHAP interpretability.

Accurate risk stratification is essential for guiding treatment decisions and preventing over treatment of prostate cancer, which remains one of the most prevalent cancers among adult men. While the Gleason score, obtained from prostate biopsies, is routinely used to assess tumor aggressiveness, the biopsy procedure carries risks such as pain, infection, and, in some cases, serious complications such as sepsis. In this study, we proposed an artificial intelligence-based framework that integrates mRNA expression profiles with functional interaction networks to classify prostate cancer patients into low-, medium-, and high-risk groups defined by Gleason scores. The pipeline comprised five steps: (1) data collection from The Cancer Genome Atlas (TCGA), (2) preprocessing of gene expression data, (3) two-stage feature selection to identify informative biomarkers, (4) risk classification using a dual-branch graph neural network (GNN) that combines gene-gene interaction graphs with sample-level expression features, and (5) model interpretation using SHAP to quantify feature contributions. Differentially expressed genes were identified in the High (ASPN, GMNN, PEBP4, C2, KNCK17), Medium (C2, IGSF1, ASPN, CDKN3, AMH), and Low (TNMD, VWA5B2, ST6GALNAC5, CYP3A5, PHGR1) risk groups, underscoring the molecular heterogeneity of disease progression. On an independent held-out test set, the model achieved AUCs of 0.86, 0.88, and 0.95 for the low-, medium-, and high-risk groups, respectively, with an overall accuracy of 80%. These results suggest that combining GNN-based modeling with explainable AI can capture both global and local molecular patterns relevant to tumor aggressiveness. However, as the model was developed and evaluated solely on the TCGA cohort, the findings should be regarded as exploratory, and external validation will be required to establish generalizability. Within these limitations, the proposed framework highlights the potential of molecular profiling and graph-based deep learning to support more precise, potentially less invasive, risk assessment and individualized treatment planning in prostate cancer.

Prostatic Neoplasms↗

Risk stratification and prognostic implication of plasma biomarkers in nondiabetic patients with stable coronary artery disease: the role of high-sensitivity C-reactive protein.

STUDY OBJECTIVES: To evaluate the implication of plasma biomarkers to future cardiovascular events in nondiabetic patients with stable coronary artery disease (CAD). Designs and settings: Prospective, follow-up study at a tertiary referral center. Patients and measurement: Serial plasma biomarkers including high-sensitivity C-reactive protein (hsCRP), homocysteine, soluble adhesion molecules, von Willebrand factor, and lipid profiles were determined before coronary angiograms in a series of nondiabetic CAD patients with stable angina. Among them, 75 consecutive patients who received coronary revascularization (48 coronary interventions and 27 coronary bypass surgeries) later and another 75 age- and gender-matched patients who preferred medical treatment were both enrolled. In patients of each group, major cardiovascular events including cardiac death, nonfatal myocardial infarction, new or repeated coronary revascularization, and hospitalization for unstable angina, stroke, or peripheral artery disease were prospectively followed up for at least 6 months. RESULTS: Patients were followed up to 40 months (median, 18 months). The incidences of major cardiovascular events were similar between the two groups. For patients with medical treatment, plasma levels of hsCRP, homocysteine, low-density lipoprotein, and the ratio of total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) were significantly higher in those with cardiovascular events than those without. However, only hsCRP > 0.1 mg/dL (relative risk [RR], 2.78; 95% confidence interval [CI], 1.21 to 6.41; p = 0.016) and TC/HDL-C ratio > 4.8 (RR, 2.42; 95% CI, 1.04 to 5.65; p = 0.041) were independent predictors by multivariable analysis. For patients with revascularization, basal plasma hsCRP levels were higher in those with cardiovascular events than those without (p = 0.04). However, no biochemical markers could predict future major cardiovascular events in these patients. CONCLUSIONS: In nondiabetic patients with CAD, basal plasma hsCRP levels were increased with future cardiovascular events regardless of different treatment strategies. Both plasma hsCRP level and TC/HDL-C ratio independently predict future cardiovascular events, confirming the role of plasma biomarkers in clinical risk stratification especially in patients with medical treatment.

Aged↗

Prolonged intubation rates after coronary artery bypass surgery and ICU risk stratification score.

OBJECTIVE: To determine prolonged intubation rates among patients undergoing coronary artery bypass graft (CABG) surgery, and to evaluate the ability of the Intensive Care Unit Risk Stratification Score (ICURSS) model to predict these events. DESIGN: Prospective observational study. SETTING: A 24-bed ICU in a tertiary referral university hospital. PATIENTS: Five hundred sixty-nine patients undergoing CABG surgery. INTERVENTIONS: Variables of the ICURSS model were recorded at ICU admission. Extubation was performed according to a standard protocol. Patients remaining intubated within 8 h after ICU admission were designated as having early extubation failure (EEF). The next evaluations at 16, 24, 48, 72, and 96 h designated patients as having a prolonged intubation period (PIP) and prolonged mechanical ventilation (PMV) for 24, 48, 72, and 96 h. The ability of the ICURSS model to predict extubation failure at different cutoff values was measured using the Hosmer-Lemeshow goodness-of-fit test and the area under the receiver operating characteristic curve. MEASUREMENTS AND RESULTS: Prolonged intubation rates were as follows: EEF, 40.2%; PIP, 17.2%; PMV for 24 h, 10.4%; PMV for 48 h, 7.6%; PMV for 72 h, 6.5%; and PMV for 96 h, 6.0%. At every cutoff, the ICURSS showed poor discrimination to predict the failure to be extubated. Calibration was also poor, although some ability to predict both EEF and PMV at > or = 48 h was shown. CONCLUSIONS: Prolonged intubation rates after undergoing CABG surgery in our setting were comparable with those of other reports from institutions where fast-track cardiac anesthesia is currently in practice. In our cohort, the ICURSS was not useful for the prediction of length of intubation.

Aged↗

Stratification by risk factors predicts survival on the active treatment arm in a randomized phase II study of interferon-gamma plus/minus interferon-alpha in advanced renal cell carcinoma (E6890).

INTRODUCTION: Standard therapy for recurrent or metastatic renal carcinoma includes the biologic response modifiers interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). The response rate for both agents is modest and toxicity is significant. New agents are needed. Interferon-gamma (IFN-gamma) is a type II interferon that demonstrated promising activity in renal carcinoma in early clinical trials. In vitro data suggested synergistic activity when IFN-gamma was combined with IFN-alpha. The Eastern Cooperative Oncology Group conducted a randomized phase II trial to confirm the efficacy of IFN-gamma as a single agent and to evaluate the efficacy and toxicity of IFN-gamma in combination with IFN-alpha in the treatment of patients with metastatic or recurrent renal carcinomas. MATERIALS AND METHODS: Ninety-five patients with recurrent or metastatic renal carcinoma were entered on trial. Patients were stratified based on risk assessment using the Elson method. Patients were randomly assigned to receive either IFN-gamma 0.1 mg/m2 weekly (arm A) or IFN-gamma 0.3 mg/m2 iv daily x 5 every 3 wk plus IFN-alpha 10 MU/m2 daily (arm B). Treatment efficacy was evaluated every 6 weeks. RESULTS: Toxicity in the arm A was minimal. Significant toxicity was noted in arm B, with four cases of grade 4 neurotoxicity. No responses were seen with IFN-gamma alone. Five responses (two CR and three PR) were noted in the combination arm for an overall response rate of 10%. Four of five responders were classified as "good risk." Median survival for arm A was 7.0 mo vs 10.4 mo for arm B. Risk stratification was significant in arm B. CONCLUSION: IFN-gamma at this dose and schedule failed to demonstrate activity in metastatic/recurrent renal carcinoma. The combination of IFN-gamma and IFN-alpha demonstrated a response rate similar to IFN-alpha alone. There was no evidence of synergy between IFN-gamma and IFN-alpha.

Adult↗

Molecular cytogenetic stratification of recurrent oligodendrogliomas: utility of interphase fluorescence in situ hybridization (I-FISH).

In oligodendroglial brain tumours, losses of chromosomal material of the short arm of chromosome 1 and long arm of chromosome 19 have been shown to predict responsiveness to chemotherapy and prolonged patients' survival. Therefore, the correct diagnosis of these genetic alterations in tumours of oligodendroglial origin is particularly important. To detect deletions of 1p36 and/or 19q13.3 in oligodendroglial cells we used dual-colour I-FISH with locus-specific DNA probes. I-FISH was performed on isolated whole cell nuclei, prepared from fresh non-fixed tumour tissue samples resuspended in media and processed using a standard cytogenetic procedure, thus bypassing the problem of nuclear truncation. We examined 16 patients with histologically proved oligodendrogliomas (5x oligodendroglioma, 9x anaplastic oligodendroglioma, 2x anaplastic oligoastrocytoma). The results of molecular cytogenetic analyses were correlated with morphological and clinical findings. Molecular cytogenetic analyses were successful in 15 patients and, due to a non-adequate tissue specimen, were uninformative in one patient only. Combined deletions 1p36/19q13 were proved in 13 patients. However, in six of them additional genetic alterations typical for high-grade astrocytoma were found, which could have negative influence on the prognosis. One patient had isolated deletion of 1p36 and another had a normal genetic pattern without any chromosomal alterations. In summary, I-FISH on isolated cell nuclei is a powerful tool for detecting chromosomal aberrations in tumour cells. A systematic molecular cytogenetic analysis may advance diagnosis, prognostic stratification, and targeted treatment of patients with brain tumours.

Adult↗

Stratification of acute myeloid leukemia based on gene expression profiles.

Acute myeloid leukemia (AML) is characterized by clonal growth of immature leukemic blasts and develops either de novo or secondarily to anticancer treatment or to other hematologic disorders. Given that the current classification of AML, which is based on blast karyotype and morphology, is not sufficiently robust to predict the prognosis of each affected individual, new stratification schemes that are of better prognostic value are needed. Global profiling of gene expression in AML blasts has the potential both to identify a small number of genes whose expression is associated with clinical outcome and to provide insight into the molecular pathogenesis of this condition. Emerging genomics tools, especially DNA microarray analysis, have been applied in attempts to isolate new molecular markers for the differential diagnosis of AML and to identify genes that contribute to leukemogenesis. Progress in bioinformatics has also yielded means with which to classify patients according to clinical parameters such as long-term prognosis. The application of such analysis to large sets of gene expression data has begun to provide the basis for a new AML classification that is more powerful with regard to prediction of prognosis.

Biomarkers, Tumor↗

National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification.

OBJECTIVES: A series of new guidelines has been developed by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative to improve the detection and management of chronic kidney disease (CKD). In most instances of CKD, the earliest manifestations of the disorder may be identified by relatively simple tests. Unfortunately, CKD is often "underdiagnosed," in part because of the absence of a common definition of CKD and a classification of the stages in its progression. The Kidney Disease Outcomes Quality Initiative clinical practice guidelines for CKD evaluation, classification, and stratification provide a basis to remedy these deficits. The specific goals of the guidelines described in this review are to provide: 1) an overview of the clinical practice guidelines as they pertain to children and adolescents, 2) a simple classification of the stages of CKD, and 3) a practical approach to the laboratory assessment of kidney disease in children and adolescents. METHODS: The guidelines were developed as part of an evidence-based evaluation of CKD and its consequences in patients of all ages. The data that were used to generate the guidelines in this article were extracted from a structured analysis of articles that reported on children with CKD. RESULTS AND CONCLUSIONS: This review presents the definition and 5-stage classification system of CKD developed by the work group assigned to develop the guidelines, and summarizes the major recommendations regarding the early detection of CKD. Major emphasis is placed on the identification of children and adolescents with CKD by measuring the protein-to-creatinine ratio in spot urine specimens and by estimating the glomerular filtration rate from serum creatinine using prediction equations.

Adolescent↗

N-terminal proBNP: a novel biomarker for the diagnosis, risk stratification and management of congestive heart failure.

Congestive heart failure is a leading cause of morbidity and mortality throughout the world and is now the leading cause of hospitalizations in adults over 65 years of age with an estimated annual expenditure in excess of USD 20 billion. In addition, it is the only cardiovascular disorder that continues to increase in both incidence and prevalence, and as the population continues to age, it is expected that the prevalence of this disease will continue to rise. Ironically, the armamentarium of medications that decrease mortality due to congestive heart failure also continues to grow; however, the relative number of eligible patients with congestive heart failure (or at risk for congestive heart failure) that receive these important therapies remains low. Thus, better tools to aid the early diagnosis and management of this disease are needed. Testing for natriuretic peptide markers, such as B-type natriuretic peptide or its amino-terminal fragment, has emerged as an important tool to assist in the optimal diagnosis and risk stratification of patients with congestive heart failure and may also play a valuable role in guiding therapy.

Biomarkers↗

Distribution of cardiac geometric patterns on echocardiography in essential hypertension. Impact of two criteria of stratification.

PURPOSE: To evaluate 2 left ventricular mass index (LVMI) normality criteria for the prevalence of left ventricular geometric patterns in a hypertensive population ( HT ). METHODS: 544 essential hypertensive patients, were evaluated by echocardiography, and different left ventricular hypertrophy criteria were applied: 1 - classic : men - 134 g/m2 and women - 110 g/m2; 2- obtained from the 95th percentil of LVMI from a normotensive population (NT). RESULTS: The prevalence of 4 left ventricular geometric patterns, respectively for criteria 1 and 2, were: normal geometry - 47.7% and 39.3%; concentric remodelying - 25.4% and 14.3%; concentric hypertrophy - 18.4% and 27.7% and excentric hypertrophy - 8.8% and 16.7%, which confered abnormal geometry to 52.6% and 60.7% of hypertensive. The comparative analysis between NT and normal geometry hypertensive group according to criteria 1, detected significative stuctural differences,"( *p < 0.05):LVMI- 78.4 +/- 1.50 vs 85.9 +/-0.95 g/m2 *; posterior wall thickness -8.5 +/- 0.1 vs 8.9 +/- 0.05 mm*; left atrium - 33.3 +/- 0.41 vs 34.7 +/- 0.30 mm *. With criteria 2, significative structural differences between the 2 groups were not observed. CONCLUSION: The use of a reference population based criteria, increased the abnormal left ventricular geometry prevalence in hypertensive patients and seemed more appropriate for left ventricular hypertrophy detection and risk stratification.

Analysis of Variance↗

[Score for nutritional status evaluation: the role played in the prognostic stratification of dilated cardiomyopathy and advanced heart failure patients].

OBJECTIVE: Develop a method for the evaluation of patients nutritional status through a score that expresses universal nutritional status, as well as investigate if that score would be efficient for the prognostic stratification of advanced heart failure (HF) pts. METHODS: The score was reached by the selection of evaluation methods that would quantify nutritional status: ideal body weight percentage, thickness of tricipital skinfold, percentiles for arm muscular mass circumference, albumin serum level, lymphocyte total count. In order to be validated, the score was applied to a group of 95 pts. Pts were under 65 years old no evidence of consumptive diseases. The score was analyzed to confirm whether it would keep correlation with HF clinical data and whether it would stratify its prognostic. RESULTS: Nutritional status suggesting moderate or severe malnutrition could be observed in 31/95 (32.6%). No correlation was found between nutritional score values and the duration of symptoms, or the level of ventricular dysfunction. Pts with high nutritional score showed a trend towards higher mortality rate (p=0.0606). CONCLUSION: Those data suggest malnutrition is reported by 1/3 of pts with advanced HF. A score comprising 5 parameters for nutritional status showed good correlation with the clinical, global evaluation of pts with HF. A score over 8 identified pts with higher probability of death as outcome, confirming that pts under higher malnutrition exhibit worse evolution.

Adolescent↗

[Ecologic aspects of American tegumentary leishmaniasis. 5. Stratification of the spatial and seasonal activities of Phlebotominae (Diptera, Psychodidae) in areas of agricultural culture of the Vale do Ribeira region, State of São Paulo, Brazil].

This paper deals with the investigation on the composition and stratification of the Phebotominae activity developed in patch and clear areas of high agricultural activity. The employment of a CDC light trap proved to be a useful tool in determining the local faune. Thirteen species of sandflies and a total of 5,423 individuals were caught. The catch places situated in the ecotone were the ones in which the results reached their best, being outstanding for Psychodopygus intermedius, Lutzomyia migonei and L. fischeri. Thereby, data lead us to believe they have acrodendrophilous habit. On the other hand, when the global results were gathered according to male and female categories, the first one proved to be predominant. In the analysis of seasonal distribution for the three species cited, it was clear that the high-activity peaks were bi- and tri-modal for different seasons. P. intermedius was almost the exclusive sandfly caught at ground level in the Autumn season. This exclusiveness has practically extended itself to the catch places situated in open field.

Animals↗

Epidemiological risk stratification of malaria in the Americas.

During the last years, malaria had a significant increase in Latin America, emerging again as one critical health problem in the Region of the Americas. More than 1.04 million new cases were reported in 1990. This resurgence of malaria needed a comprehensive strategy for its prevention and control. National malaria control programs recognized the epidemiological stratification of malaria as a valuable method to assist them in the recognition of local variations and factors that specifically contribute to the level and intensity of transmission in critical malarious areas. Also it serves as a useful instrument for the selection of needed malaria prevention and control activities. The principal feature of this approach is to provide a dynamic and ongoing process for assessing the epidemiological importance of different risk factors (socio-economic, ecological, organization of health services) in malaria transmission. Health interventions are based on this assessment and are aimed directly at the reduction or elimination of the identified risk factors operating at the local level. Intersectorial co-participation and the integration of malaria programs in local health services are also important aspects of this public health approach.

Epidemiologic Methods↗

Horizontal stratification of the sand fly fauna (Diptera: Psychodidae) in a transitional vegetation between caatinga and tropical rain forest, state of Bahia, Brazil.

A study about the horizontal stratification of the sand fly fauna in two distinct ecosystems, caatinga area, endemic for visceral leishmaniasis, and the tropical rain forest area, endemic for cutaneous leishmaniasis, was performed in the state of Bahia, Brazil. Lutzomyia longipalpis was predominant in the caatinga, and following it came the species L. capixaba and L. oswaldoi. In the tropical rain forest other species were found, such as L. intermedia, L. migonei, L. whitmani, L. yuilli, L.fischeri, L. damascenoi, L. evandroi, L. monticola, and L. lenti. It was found that the geographical limits of the vector species of visceral and cutaneous leishmaniasis are clearly defined by the biological and phytogeographic characteristics.

Animals↗

Clinical practice guidelines in nephrology: evaluation, classification, and stratification of chronic kidney disease.

The National Kidney Foundation developed and oversees the Kidney Disease Outcomes Quality Initiative, a process that develops clinical practice guidelines in nephrology. Recent guidelines address the evaluation, classification, and stratification of chronic kidney disease (CKD). These guidelines provide, for the first time, a standard definition of CKD, classification of its stages, and suggestions for appropriate laboratory measurements for the assessment of kidney function. Also discussed are the association of level of kidney function with systemic complications that develop during CKD, and the risk of loss of kidney function and development of cardiovascular disease in CKD.

Chronic Disease↗

The neural organization of the pineal complex in the frog: stratification and regional differences.

Plexiform areas are functionally important units of the pineal complex. The silver impregnation technique by Matsuyama (1972) reveals in the frog that nerve fibres branch and terminate in these areas and that they are presynaptic to nerve cells which are part of the plexiform areas. Histochemically, the nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) method according to Scherer-Singler et al. (1983) indicates that pinealocytes and nerve cells are both stained, a strong stratification of different cell types can be visualized. Plexiform areas of different size exist at the dorsal and ventral surface of the organ; the biggest are located rostrodorsally. Approximately twenty large multipolar nerve cells are localized at the ventral surface of the pineal organ mainly at the rostral and lateral borders. They send long processes mainly in caudal direction. These processes are post-synaptic to the boutons of the endfeet belonging to photosensitive pinealocytes. Processes of several multipolar nerve cells converge to one plexiform area, branch and obviously terminate there. As in horizontal cells the processes of the multipolar cells seem to be capable of both receiving and transmitting signals. On the postsynaptic side of the processes of the multipolar cells are smaller nerve cells juxtaposed to the plexiform areas. They are known as pseudounipolar, unipolar or bipolar cells (Wake et al., 1974); the latter are free of boutons of the pinealocytes, their axons forming the pineal tract. Three different types of photosensitive pinealocytes can be distinguished: a slender, a spherical and a double-cone type. Also, the number of boutons varies in the endfeet: boutons occur alone, in groups of two or three, and in clusters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗